CLSI VET08

C L S I V E T 0 1 S G e n e r i c A d m i n V E T 0 1 S 3 F N G e n e r i c A d m i n V E T 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

4th Edition

VET08 Performance Standards Standards for Antimi Antimicrobial crobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals

This document includes updated tables for the Clinical and Laboratory Standards Institute veterinary antimicrobial susceptibility susceptibi lity testing standard s tandard VET01. A CLSI supplement for global application.


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Do you use CLSI documents in your workplace? Do you see room for improvement? Would you like to get involved in the revision process? Or maybe you see a need to develop a new document for an emerging technology? CLSI wants to hear from you. We are always looking for volunteers. By donating your time and talents to improve the standards that affect your own work, you will play an active role in improving public health across the globe. For additional information on committee participation or to submit comments, contact CLSI. Clinical and Laboratory Standards Institute 950 West Valley Road, Suite 2500 Wayne, PA 19087 USA P: +1.610.688.0100 F: +1.610.688.0700 www.clsi.org [email protected]


VET08, 4th ed. June 2018 Replaces VET01S, 3rd ed.

Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals Brian V. Lubbers, DVM, PhD, DACVCP Mark G. Papich, DVM, MS Stefan Schwarz, DVM Robert Bowden, BS Dubraska V. Diaz-Campos, DVM, PhD Mark Fielder, PhD Cory Langston, DVM, PhD Xian-Zhi Li, PhD Marilyn N. Martinez, PhD

Claire Miller, DVM, PhD, DACVM Ian Morrissey, PhD Christine Pallotta, MS, BS Thomas R. Shryock, PhD Shabbir Simjee, MSc, PhD Virginia Sinnott-Stutzman, DVM, DACVECC Michael T. Sweeney, MS Maria M. Traczewski, BS, MT(ASCP) Darren Trott, PhD S. Steve Yan, PhD

Abstract The data in the tables are valid only if the methodologies in CLSI document VET01 1 are followed. This standard contains information about disk and dilution test procedures for aerobic and facultatively facultatively anaerobic bacteria. Clinicians depend heavily on information from the microbiology laboratory for treating their seriously ill patients. The clinical importance of antimicrobial susceptibility test results demands that these tests be performed under optimal conditions and that laboratories have the capability to provide results for the newest antimicrobial agents. The tables presented in VET08 represent the most current information for drug selection, interpretation, interpretation, and quality control u sing 1 the procedures standardized in VET01. Users should replace previously published tables with these new tables. Changes in the tables since the previous editions appear in boldface type. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals. 4th Animals. 4th ed. CLSI supplement VET08 (ISBN 978-1-68440-010-2 [Print]; ISBN 978-1-68440 011-9 [Electronic]). Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087 USA, 2018. The Clinical and Laboratory Standards Institute consensus process, which is the mechanism for moving a document through two or more levels of review by the health care community, is an ongoing process. Users should expect revised editions of any given document. Because rapid changes in technology may affect the procedures, methods, and protocols in a standard or guideline, users should replace outdated editions with the current editions of CLSI documents. Current editions are listed in the CLSI catalog and posted on our website at www.clsi.org. If you or your organization is not a member and would like to become one, or to request a copy of the catalog, contact us at: Telephone: +1.610.688.0100; Fax: +1.610.688.0700; E-Mail: [email protected]; [email protected]; Website: www.clsi.org.


VET08, 4th ed.

Copyright ©2018 Clinical and Laboratory Standards Institute. Except as stated below, any reproduction of content from a CLSI copyrighted standard, guideline, derivative product, or other material requires express written consent from CLSI. All rights reserved. Interested parties may send permission requests to [email protected]. CLSI hereby grants permission to each individual member or purchaser to make a single reproduction of this publication for use in its laboratory procedures manual at a single site. To request permission to use this publication in any other manner, e-mail [email protected].

Suggested Citation CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals. 4th Animals. 4th ed. CLSI supplement VET08. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. Previous Editions: May 2004, July 2013, June 2015

ISBN 978-1-68440-010-2 (Print) ISBN 978-1-68440-011-9 (Electronic) ISSN 1558-6502 (Print) ISSN 2162-2914 (Electronic)

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Volume 38, Number 14


VET08, 4th ed.

Committee Membership Subcommittee on Veterinary Antimicrobial Susceptibility Testing Brian V. Lubbers, DVM, PhD, DACVCP Chairholder Kansas State Veterinary Diagnostic Laboratory USA Mark G. Papich, DVM, MS Vice-Chairholder College of Veterinary Medicine, North Carolina State University USA Stefan Schwarz, DVM Committee Secretary Freie Universit ät Berlin Germany

Dubraska V. Diaz-Campos, DVM, PhD College of Veterinary Medicine, The Ohio State University, USA

Mark Fielder, PhD School of Life Science, Kingston University London United Kingdom Cory Langston, DVM, PhD Mississippi State University USA

Thomas R. Shryock, PhD Antimicrobial Consultants, LLC USA Shabbir Simjee, MSc, PhD Elanco Animal Health United Kingdom

Xian-Zhi Li, PhD Health Canada Veterinary Drugs Directorate Canada

Virginia Sinnott-Stutzman, DVM, DACVECC Angell Animal Medical Center (MSPCA) USA

Marilyn N. Martinez, PhD FDA Center for Veterinary Medicine USA

Michael T. Sweeney, MS Zoetis USA

Ian Morrissey, PhD IHMA Europe Sarl Switzerland

Darren Trott, PhD School of Animal and Veterinary Sciences, University of Adelaide, Australia

Christine Pallotta, MS, BS Thermo Fisher Scientific USA

Acknowledgment

CLSI and the Subcommittee on Veterinary Antimicrobial Susceptibility Testing gratefully acknowledge the following volunteers for their important contributions to the development of this document: Robert Bowden, BS University of Florida Veterinary Diagnostic Laboratories USA

Maria M. Traczewski, BS, MT(ASCP) The Clinical Microbiology Institute USA

Claire Miller, DVW, PhD, DACVM Washington State University USA

S. Steve Yan, PhD FDA Center for Veterinary Medicine

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VET08, 4th ed.

Working Group on Editorial/VAST Breakpoint Tables Michael T. Sweeney, MS Chairholder Zoetis USA

Thomas R. Fritsche, MD, PhD, FCAP, FIDSA Marshfield Clinic USA

Markus Rose, DVM, PhD MSD Animal Health Intervet Innovation GmbH Germany

Maria M. Traczewski, BS, MT(ASCP) Vice-Chairholder, Committee Secretary The Clinical Microbiology Microbiology Institute USA

Claire Miller, DVM, PhD, DACVM Washington State University USA

Stefan Schwarz, DVM Freie Universität Berlin Germany

Christine Pallotta, MS, BS Thermo Fisher Scientific USA

Virginia Sinnott-Stutzman, DVM, DACVECC Angell Animal Medical Center (MSPCA) USA

Robert Bowden, BS University of Florida Veterinary Diagnostic Laboratories USA Dubraska V. Diaz-Campos, DVM, PhD College of Veterinary Medicine, The Ohio State University, USA

Mark G. Papich, DVM, MS College of Veterinary Medicine, North Carolina State University USA Anne Parkinson, BS Ohio Animal Disease Diagnostic Laboratory USA

Ching Ching Wu, DVM, PhD National Taiwan University, University, School of Veterinary Medicine Taiwan S. Steve Yan, PhD FDA Center for Veterinary Medicine USA

Staff

Clinical and Laboratory Standards Institute USA Lori T. Moon, MS, MT(ASCP) Project Manager

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Megan L. Tertel, MA, ELS Editorial Manager

Kristy L. Leirer, MS Editor

Catherine E.M. Jenkins Editor

Laura Martin Editor


VET08, 4th ed.

Contents

Abstract ................................................................................................................................................... i

s t n e t n o C f o e l b a T

Committee Membership .........................................................................................................................iii Overview of Changes ...........................................................................................................................viii Summary of CLSI Processes for Establishing Breakpoints and Quality Quality Control Ranges ................ .. xxi CLSI Reference Methods vs Commercial Methods and CLSI vs Regulatory Authority .................. .xxi xxii CLSI Veterinary-Specific Breakpoint Additions/Revisions Since 2015 ............ .................... ...........xx xxiii Subcommittee on Veterinary Antimicrobial Susceptibility Testing Mission Statement and Responsibilities .................................................................................................................................. .. xxv Instructions for Use of Tables .................. .................. ................... .................... ................... ................... 1 References ............................................................................................................................................. 13 Table 1. Antimicrobial Agents That Could Be Considered for Routine Testing by Veterinary Microbiology Laboratories ................................................................................................................... 14 Table 2A. Zone Diameter and MIC Breakpoints for Enterobacteriacea for Enterobacteriaceaee ............................................20 Table 2B. Zone Diameter and MIC Breakpoints for Pseudomonas for Pseudomonas aeruginosa aeruginosa ..................................34 Table 2C. Zone Diameter and MIC Breakpoints for Staphylococcus spp. Staphylococcus spp. ................. ................. ......... 38 Table 2D. Zone Diameter and MIC Breakpoints for Streptococcus spp. Streptococcus spp. ............ ................. ................ 54 Table 2E. Zone Diameter and MIC Breakpoints for Enterococcus for Enterococcus spp. spp................................................ ............................................... 68 Table 2F. Zone Diameter and MIC Breakpoints for Bordetella for Bordetella bronchiseptica bronchiseptica ........... ............................ ................. ...... 74 Table 2G. Zone Diameter and MIC Breakpoints for Mannheimia for Mannheimia haemolytica haemolytica ................ ................. .. 76 Table 2H. Zone Diameter and MIC Breakpoints for Pasteurella for Pasteurella multocida multocida ........................................ ........................................80 Table 2I. Zone Diameter and MIC Breakpoints for Actinobacillus for Actinobacillus pleuropneumoniae pleuropneumoniae ................ ....... 86 Table 2J. Zone Diameter and MIC Breakpoints for Histophilus for Histophilus somni somni ................................................ ................................................90 Table 3. QC Strain Culture Collection Numbers for Antimicrobial Susceptibility Susceptibility Tests ................... .. 94 Table 4A. Disk Diffusion QC Ranges for Nonfastidious Nonfastidious Organisms ................. ................... ...............96 Table 4B. Disk Diffusion QC Ranges for Fastidious Organisms .........................................................98 Table 4C. Disk Diffusion Reference Guide to QC Frequency................... ................... .................... ..100 Table 4D. Disk Diffusion Troubleshooting Guide.................... ................... ................... ....................102

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Contents (Continued) Table 5A. MIC QC Ranges for Nonfastidious Organisms .................................................................106 s t n e t n o C f o e l b a T

Table 5B. MIC QC Ranges for Fastidious Organisms (Broth Dilution Methods) .............................. ............... ............... 108 Table 5C. MIC QC Ranges for Anaerobes (Agar Dilution Method) ................. ................. ................ 110 Table 5D. MIC QC Ranges for Anaerobes (Broth Microdilution Method) .............................. ............... ......................... .......... 112 Table 5E. MIC Reference Guide to QC Frequency .................................. ................. .................. ....... 114 Table 5F. MIC Troubleshooting Guide.................. ................... .................... ................... .............. ..... 116 Table 6. Solvents and Diluents for Preparing Stock Solutions of Antimicrobial Agents ................... 1 2 0 Table 7A. Disk Diffusion Tests for Extended-Spectrum -Lactamases in Klebsiella in Klebsiella pneumoniae, Klebsiella Klebsiella oxytoca, Escherichia coli, coli, and Proteus and Proteus mirabilis mirabilis ............................. ............ 122 Table 7B. Broth Microdilution Tests for Extended-Spectrum -Lactamases in Klebsiella in Klebsiella pneumoniae, Klebsiella Klebsiella oxytoca, Escherichia coli, coli, and Proteus and Proteus mirabilis mirabilis ............................. ............ 124 Table 7C. Test for Detection of β-Lactamase Production in Staphylococcus spp. Staphylococcus spp. ............ ................. 126 Table 7D. Disk Diffusion Test for Prediction of mecA-Mediated Resistance in Staphylococci ........ 1 30 Table 7E. Vancomycin Agar Screen for Staphylococcus aureus and aureus and Enterococcus Enterococcus spp.................. .. 132 Table 7F. Test for Detection of Inducible Clindamycin Resistance in Staphylococcus spp., Staphylococcus spp., Streptococcus spp. -Hemolytic Group, and Streptococcus pneumoniae ............. pneumoniae .............................. ................. ............ 134 Table 7G. Test for Detection of High-Level Aminoglycoside Aminoglycoside Resistance in Enterococcus spp. Enterococcus spp. (Includes Disk Diffusion) ................................................................................................................... 136 Appendix A. Suggestions for Confirming Resistant, I ntermediate, or Nonsusceptible Antimicrobial Susceptibility Test R esults and Organism Identification................. ................... ......... 138 Appendix B. Intrinsic Resistance.................. ................. ................... .................... ................... ........... 142 Appendix C. QC Strains for Antimicrobial Susceptibility Tests .............................. ................. ......... 148 Appendix D. Epidemiological Cutoff Values .................. ................. ................... .................... ........... 152 Appendix E. CLSI Veterinary-Specific Breakpoint Additions/Revisions Additions/Revisions to VET01 Supplements Since 1999 ..................................................................................................................... 154 Glossary I. Antimicrobial Class and Subclass Designations, Antimicrobial Agents, and Antimicrobial Resistance Mechanisms ................... ................. ................... ................... ................ ..... 160 Glossary II. Abbreviations Commonly Used for Antimicrobial Agents Incorporated Into Disks or Susceptibility Panels ............................................................................................................. 164 Glossary III. List of Identical Abbreviations Used for More Than One Antimicrobial Agent in US Diagnostic Products ....................................................................................................... 166

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VET08, 4th ed.

Contents (Continued) The Quality Management System Approach ................. ................... ................... .................... ........... 168 s t n e t n o C f o e l b a T

Related CLSI Reference Materials ..................................................................................................... 170

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VET08, 4th ed.

Overview of Changes s e g n a h C f o w e i v r e v O

This supplement replaces the previous edition of the supplement, VET01S, 3rd ed., published in 2015. This list includes the major changes in this document. Other minor or editorial changes were made to the general formatting and to some of the table footnotes and comments. Changes to the tables since the previous edition appear in boldface type. The following are additions or changes unless otherwise noted as a “deletion.” 

General: – Changed document code from VET01S to VET08 to differentiate it from the methods standard, CLSI document VET01 1

– Harmonized language and common information on methods and QC with CLSI documents M02 and the M02 the M02 Disk Diffusion Diffusion Reading Guide, Guide, 3 M07,4 and M1005

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– Revised nomenclature: o Clostridium difficile to Clostridioides (formerly Clostridium) Clostridium) difficile Enterobacter aerogenes aerogenes to to Klebsiella Klebsiella (formerly Enterobacter (formerly Enterobacter ) aerogenes o -lactam/ -lactam/-lactamase inhibitor combinations to -lactam combination agents o Folate pathway inhibitor to folate pathway antagonist o o Methicillin-resistant Staphylococcus aureus (MRSA) aureus (MRSA) salt agar to oxacillin salt agar To align with the International Organization for Standardization, changed the name of the o inoculum preparation method in all appropriate tables from growth method to broth culture method and changed direct colony suspension to colony suspension 

Moved to CLSI document VET066: – Testing conditions for Campylobacter spp. spp. and Listeria and Listeria spp. spp. (formerly in Table 7) – Campylobacter QC QC (formerly in Table 5B)

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Summary of CLSI Processes for Establishing Breakpoints and Quality Control Ranges (p. xxi): – Added new section

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CLSI Reference Methods vs Commercial Methods and CLSI vs Regulatory Authority (p. xxii): – Added new section

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CLSI Veterinary-Specific Breakpoint Additions/Revisions Since 2015 (p. xxiii): – Added new table of breakpoint additions and revisions since 2015, organized in order of appearance in the tables by organism group (2A, 2B, 2C, etc.) and animal species, and in alphabetical order by antimicrobial agent within the animal species (see bullets for Tables 2A through 2J for specific new breakpoints)

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Subcommittee on Veterinary Antimicrobial Susceptibility Testing Mission Statement and Responsibilities (p. xxv): – Added new section

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VET08, 4th ed.

Overview of Changes (Continued) 

Instructions for Use of Tables: – Added new section with general instructions for using the tables, including: Selecting antimicrobial agents for testing and reporting (p. 1) o Breakpoints and interpretive category definitions (p. 3) o o Reporting results (p. 5) Therapy-related comments (p. 6) o Confirmation of patient results (p. 6) o Development of resistance and testing of repeat isolates (p. 6) o Warning (misleading results) (p. 7) o o Routine, supplemental, screening, surrogate agent, and equivalent agent testing to determine susceptibility and resistance to antimicrobial agents (p. 7) QC overview (p. 10) o Abbreviations and acronyms (p. 11) o

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Table 1. Antimicrobial Agents That Could Be Considered for Routine Testing by Veterinary Microbiology Laboratories: Group A: Cattle: Added ampicillin (p. 14) o Horses: Added enrofloxacin, doxycycline, and minocycline (p. 14) o Dogs and cats: Added ampicillin (cats only), piperacillin-tazobactam (dogs only), cefovecin, o cephalexin (dogs only), minocycline (dogs only); removed footnote from cephalothin because it is no longer preferred to use cephalothin susceptibility to predict first-generation cephalosporin susceptibility susceptibility in dogs (p. 14) -

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Group B: o Dogs and cats: Added cephalexin (cats only) (p. 15) Group D: o Dogs and cats: Deleted cephalexin, ticarcillin, and ticarcillin-clavulanate ticarcillin-clavulanate Added NOTE referring to the new Instructions for Use of Tables (p. 16) Footnotes: o Revised footnote f to clarify that ampicillin should be tested as the class representative for aminopenicillins aminopenicillins (p. 17) Revised footnote g to note that cephalothin susceptibility tests are used to predict susceptibility o to cephapirin for bovine mastitis (p. 17)

Table 2A. Zone Diameter and MIC Breakpoints for Enterobacteriaceae: Added: References to Tables 4A and 5A for selecting recommended strains for routine QC (p. 20) o Reference to CLSI document M100 5 for modified QC of -lactam combination agents (p. 20) o Instructions for QC when using a commercial test system (p. 20) o -

Added the following human (gray-shaded) breakpoints: Kanamycin zone diameter and minimal inhibitory concentration (MIC) breakpoints published o in 1986 (p. 22) Streptomycin zone diameter breakpoints and comment published in 1986 (p. 22) o Piperacillin-tazobactam zone diameter and MIC breakpoints published in 1994 (p. 25) o

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VET08, 4th ed.

Overview of Changes (Continued) -


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Added the following veterinary-specific breakpoints: Ampicillin MIC breakpoints with dosing regimen for cats (p. 23) o Ampicillin MIC breakpoints with dosing regimen for cattle (p. 23) o o Piperacillin-tazobactam MIC breakpoints with dosing regimen for dogs (p. 24) Cephalexin and cefazolin MIC breakpoints with dosing regimen for dogs (pp. 25, 26) o o Cefovecin zone diameter and MIC breakpoints for dogs and cats (p. 26) Cefpodoxime urinary tract infection (UTI) MIC breakpoints for dogs (p. 26) o Enrofloxacin MIC breakpoints with dosing regimen for horses (p. 29) o o Doxycycline MIC breakpoints with dosing regimen for horses (p. 31) Minocycline MIC breakpoints with dosing regimen for horses (p. 31) o Revised the following breakpoints and/or comments: Revised general comment to include information on reading MIC end points for trimethoprim o and the sulfonamides (p. 20) Separated ampicillin breakpoint for skin, soft tissue MIC breakpoints from UTI MIC o breakpoints for dogs into into separate rows and reworded reworded comment (p. 22) Moved former general comment to heading before human ampicillin breakpoints (p. 23) o Clarified human (gray-shaded) breakpoints for veterinary application: o Added comment for imipenem referring to CLSI document M100 5 for comments on carbapenems (p. 28) Added body site “UTI” footnote for nitrofurantoin (p. 30) 

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Added the following comments and/or footnotes: General comment on the antimicrobial agent dose used (if not listed) for evaluation of each o veterinary-specific breakpoint (p. 20) Aminoglycosides human (gray-shaded) breakpoints comment warning about Salmonella spp. o and Shigella spp. Shigella spp. testing and reporting (p. 22) Ampicillin dosing regimen comment for skin, soft tissue MIC breakpoints for dogs (p. 22) o Ampicillin dosing regimen comment for skin, soft tissue MIC breakpoints for dogs, o emphasizing E. emphasizing E. coli and coli and other Enterobacteria other Enterobacteriaceae ceae resistance resistance to ampicillin and amoxicillin (p. 22) o Amoxicillin-clavulanate Amoxicillin-clavulanate comment for skin, soft tissue MIC breakpoints for dogs, emphasizing E. coli coli and other Enterobacteriaceae Enterobacteriaceae resistance resistance to ampicillin, amoxicillin, and amoxicillinclavulanate (p. 24) Cefazolin human (gray-shaded) breakpoints comments for therapy of infections other than o uncomplicated UTIs (p. 27) o Pradofloxacin dosing regimen comment for zone diameter and MIC breakpoints for dogs (p. 29) o Pradofloxacin dosing regimens comment for zone diameter and MIC breakpoints for cats (p. 29) Doxycycline and minocycline comment for MIC breakpoints for horses indicating tetracycline o should not be tested as a surrogate (p. 31) Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary o species because pharmacokinetic-pharmacodynamic (PK-PD) analysis does not support its use (pp. 28, 29) Footnotes in various locations to clarify human breakpoints for veterinary application (pp. 27, o 28, 30, 31) the Deleted the o

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following breakpoints: Ticarcillin-clavulanate Ticarcillin-clavulanate human (gray-shaded) zone diameter and MIC breakpoints


VET08, 4th ed.


Table 2B. Zone Diameter and MIC Breakpoints for Pseudomonas for Pseudomonas aeruginosa: aeruginosa: Added: References to Tables 4A and 5A for selecting recommended strains for routine QC (p. 34) o Reference to CLSI document M100 5 for modified QC of -lactam combination agents (p. 34) o Instructions for QC when using commercial test system (p. 34) o

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Added the following human (gray-shaded) breakpoints: Piperacillin-tazobactam zone diameter and MIC breakpoints published in 1994 (p. 36) o Added the following veterinary-specific breakpoints: Piperacillin-tazobactam MIC breakpoints with dosing regimen for dogs (p. 36) o Enrofloxacin MIC breakpoints with dosing regimen for horses (p. 36) o Clarified imipenem human (gray-shaded) breakpoint for veterinary application by adding comment referring to CLSI document M100 5 for comments on carbapenems (p. 36) Added the following comments and/or footnotes: General comments on: o Reading disk diffusion plates, zone margins, and partial inhibition inhibition (p. 34) P. aeruginosa aeruginosa developing resistance during prolonged antimicrobial therapy and that testing of repeat isolates may be warranted (p. 34) Antimicrobial agent dose used (if not listed) for evaluation of each veterinary-specific breakpoint (p. 34) o Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary species because PK-PD analysis does not support its use (p. 36)  

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Deleted the the following human (gray-shaded) breakpoints: Ticarcillin zone diameter and MIC breakpoints o o Ticarcillin-clavulanate Ticarcillin-clavulanate zone diameter and MIC breakpoints

Table 2C. Zone Diameter and MIC Breakpoints for Staphylococcus for Staphylococcus spp.: Added: o References to Tables 4A and 5A for selecting recommended strains for routine QC (p. 38) o Reference to CLSI document M100 5 for modified QC of -lactam combination agents (p. 38) Instructions for QC when using commercial test system (p. 38) o

– Revised incubation testing conditions for dilution methods to 16–20 hours (p. 38) -

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Reorganized: Penicillins by penicillinase-labile penicillins penicillins (p. 40) and penicillinase-stable penicillins (p. 42) o per organization in CLSI document document M100 5 Added the following human (gray-shaded) breakpoints: Oxacillin zone diameter and MIC breakpoints for Staphylococcus pseudintermedius published o in 2016 and for Staphylococcus schleiferi published schleiferi published in 2018 (p. 44) Azithromycin zone diameter and MIC breakpoints published in 1992 (p. 50) o o Clarithromycin zone diameter and MIC breakpoints published in 1992 (p. 50)

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Added the following veterinary-specific breakpoints: Ampicillin MIC breakpoints for Staphylococcus spp. Staphylococcus spp. with dosing regimen for cats (p. 40) o Piperacillin-tazobactam MIC breakpoints for Staphylococcus Staphylococcus spp. with dosing regimen for o dogs (p. 45) Cefovecin zone diameter and MIC breakpoints for S. pseudintermedius for pseudintermedius for dogs (p. 46) o o Cephalexin MIC breakpoints for S. aureus and aureus and S. pseudintermedius with pseudintermedius with dosing regimen for dogs (p. 46) Enrofloxacin MIC breakpoints for S. aureus with aureus with dosing regimen for horses (p. 48) o o Minocycline MIC breakpoints for S. pseudintermedius with pseudintermedius with dosing regimen for dogs (p. 51) Doxycycline MIC breakpoints for S. aureus with aureus with dosing regimen for horses (p. 51) o Minocycline MIC breakpoints for S. aureus with aureus with dosing regimen for horses (p. 52) o Revised the following breakpoints and/or comments: o Revised ampicillin MIC breakpoint comment for dogs, removing example antimicrobial agents for which ampicillin is the class representative (p. 40) Human (gray-shaded) comments for penicillinase-labile penicillins (p. 41) and penicillinaseo stable penicillins (pp. 43, 44) Clarified vancomycin human (gray-shaded) breakpoint comments for veterinary application (p. o 49) Clarified nitrofurantoin human breakpoint for veterinary application by adding body site “UTI” o (p. 50)

– Added the following comments and/or footnotes: General comments on: o Reading disk diffusion plates, zone margins, and partial inhibition (p. 38) Reading broth microdilution MIC end points with trailing growth (p. 38) Antimicrobial agent dose used (if not listed) for each veterinary-specific breakpoint evaluation (p. 38) Human (gray-shaded) comments for penicillinase-labile penicillins (p. 41) and penicillinaseo stable penicillins (pp. 42–44) o Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary species because PK-PD analysis does not support its use (pp. 47, 48) Pradofloxacin dosing regimen comment for zone diameter and MIC breakpoints for dogs (p. o 47) Pradofloxacin dosing regimens comment for zone diameter and MIC breakpoints for cats (p. o 48) Clindamycin comment on detecting inducible lincosamide resistance for dogs (p. 50) o Doxycycline and minocycline comment for MIC breakpoints for horses indicating tetracycline o should not be tested as a surrogate (pp. 51, 52) Footnotes in various locations to clarify human breakpoints for veterinary application (pp. 42– o 44, 48–51)   

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Table 2D. Zone Diameter and MIC Breakpoints for Streptococcu for Streptococcuss spp.: Added: o Medium for agar dilution method to testing conditions (p. 54) Inoculum and agar dilution method incubation conditions to testing conditions (p. 54) o o References to Tables 4B and 5B for selecting recommended strains for routine QC (p. 54) Instructions for QC when using commercial test system (p. 54) o


VET08, 4th ed.


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Added the following human (gray-shaded) breakpoints: Azithromycin zone diameter and MIC breakpoints published in 1992 (p. 63) o Clarithromycin zone diameter and MIC breakpoints published in 1992 (p. 63) o Added the following veterinary-specific breakpoints: o Ampicillin MIC breakpoints for Streptococcus spp. Streptococcus spp. with dosing regimen for cats (p. 56) Cefovecin zone diameter and MIC breakpoints for Streptococcus spp. Streptococcus spp. -hemolytic group for o dogs (p. 59) Cephalexin MIC breakpoints for Streptococcus spp. Streptococcus spp. -hemolytic group with dosing regimen o for dogs (p. 59) Enrofloxacin MIC breakpoints for Streptococcus equi subsp. equi subsp. equi and subsp. zooepidemicus subsp. zooepidemicus o with dosing regimen for horses (p. 62) o Doxycycline MIC breakpoints for S. equi subsp. equi subsp. equi and subsp. zooepidemicus subsp. zooepidemicus with with dosing regimen for horses (p. 64) o Minocycline MIC breakpoints for Streptococcus spp. with dosing regimen for horses (p. 64) Revised the following breakpoints and/or comments: o Revised ampicillin MIC breakpoint comment for dogs, removing example antimicrobial agents for which ampicillin is the class representative (p. 56) o Revised and expanded ampicillin and penicillin human (gray-shaded) breakpoint comment about unusual phenotypes and added clarification for veterinary application (p. 57) Clarified human (gray-shaded) breakpoints for veterinary application: o Added comment for imipenem referring to CLSI document M100 5 for comments on carbapenems (p. 59) Revised comments for clindamycin (p. 62), vancomycin (p. 63), and chloramphenicol (p. 64) 



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Added the following comments and/or footnotes: General comments on: Reading disk diffusion plates, zone margins, and partial inhibition inhibition (p. 54) Reading broth microdilution MIC end points with trailing growth (p. 54) Antimicrobial agent dose used (if not listed) for each veterinary-specific breakpoint evaluation (p. 54) Ampicillin and penicillin human (gray-shaded) breakpoint comment on surrogate testing (p. o 57) Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary o species because PK-PD analysis does not support its use (pp. 61, 62) Pradofloxacin dosing regimens comment for zone diameter and MIC breakpoints for cats (p. o 61) Doxycycline and minocycline comment for MIC breakpoint for horses that tetracycline should o not be tested as a surrogate (p. 64) o Footnote in various locations to clarify human breakpoints for veterinary application (p. 57, 59, 63–65) o

  



Table 2E. Zone Diameter and MIC Breakpoints for Enterococcus spp.: Added: References to Tables 4A and 5A for selecting recommended strains for routine QC (p. 68) o o Instructions for QC when using commercial test system (p. 68)

-

xiii



VET08, 4th ed.



-



-

-

xiv

Revised the ampicillin MIC breakpoint comment for swine to indicate the class representative (p. 74) Added general comment on the antimicrobial agent dose used (if not listed) for each breakpoint evaluation (p. 74)

Table 2G. Zone Diameter and MIC Breakpoints for Mannheimia for Mannheimia haemolytica: haemolytica: Added: Information to broth dilution medium testing conditions for strains of M. haemolytica that haemolytica that fail o to grow in CAMHB (p. 76) Information to inoculum preparation testing conditions (p. 76) o References to Tables 4A, 4B, 5A, and 5B for selecting recommended strains for routine QC (p. o 76) Instructions for QC when using a commercial test system (p. 76) o -



Added the following comments and/or footnotes: General comments on antimicrobial agents with difficult end-point determinations and reading o broth microdilution microdilution MIC end points with with trailing growth (p. 68) 68) o Added footnote to chloramphenicol comment to clarify human (gray-shaded) breakpoint for veterinary application (p. 71)

Table 2F. Zone Diameter and MIC Breakpoints for Bordetella for Bordetella bronchiseptica: bronchiseptica: Added: References to Tables 4A and 5A for selecting recommended strains for routine QC (p. 74) o o Instructions for QC when using commercial test system (p. 74) -



Clarified human breakpoints for veterinary application: Added and/or revised human (gray-shaded) comments for rifampin (p. 69), ampicillin and o penicillin (pp. 69, 70), vancomycin vancomycin (p. 70), and chloramphenicol chloramphenicol (p. 71) o Added body site “UTI” for nitrofurantoin (p. 70) and tetracycline (p. 71)

Added the following veterinary-specific breakpoints: Ampicillin MIC breakpoints with dosing regimen for cattle (p. 76) o o Danofloxacin intermediate and resistant zone diameter and MIC breakpoints with dosing regimen comments for cattle (p. 77) Added the following comments and/or footnotes: o General comment on the antimicrobial agent dose used (if not listed) for each breakpoint evaluation (p. 76) Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary o species because PK-PD analysis does not support its use (p. 77)

Table 2H. Zone Diameter and MIC Breakpoints for Pasteurella for Pasteurella multocida: multocida: Added: Information to inoculum preparation testing conditions (p. 80) o References to Tables 4A, 4B, 5A, and 5B for selecting recommended strains for routine QC (p. o 80) Instructions for QC when using a commercial test system (p. 80) o


VET08, 4th ed.


-

-



Revised the ampicillin MIC breakpoint comment for swine to indicate the class representative (p. 81) Added the following comments and/or footnotes: General comment on the antimicrobial agent dose used (if not listed) for each breakpoint o evaluation (p. 80) o Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary species because PK-PD analysis does not support its use (p. 82) Pradofloxacin dosing regimens comment for zone diameter and MIC breakpoints for cats (p. o 82) Footnotes in various locations to clarify human breakpoints for veterinary application (p. 83) o

Table 2I. Zone Diameter and MIC Breakpoints for Actinobacillu for Actinobacilluss pleuropneumoniae: pleuropneumoniae: Added: Reference to VET01 1 for preparation of chocolate MHA (p. 86) o o Information to inoculum preparation testing conditions (p. 86) References to Tables 4B and 5B for selecting recommended strains for routine QC (p. 86) o Instructions for QC when using a commercial test system (p. 86) o -

-



Added the following veterinary-specific breakpoints: Ampicillin MIC breakpoints with dosing regimen for cats (p. 81) o Ampicillin MIC breakpoints with dosing regimen for cattle (p. 81) o o Cefovecin zone diameter and MIC breakpoints for cats (p. 81) Danofloxacin intermediate and resistant zone diameter and MIC breakpoints with dosing o regimen comments for cattle (p. 82)

Revised the ampicillin MIC breakpoint comment for swine to indicate the class representative (p. 87) Added the following comments and/or footnotes: General comments on reading disk diffusion plates and zone margins (p. 86) o General comment on the antimicrobial agent dose used (if not listed) for each breakpoint o evaluation (p. 86) Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary o species because PK-PD analysis does not support its use (p. 87)

Table 2J. Zone Diameter and MIC Breakpoints for Histophilu for Histophiluss somni: Added: o Reference to VET01 1 for preparation of chocolate MHA (p. 90) Information to inoculum preparation testing conditions (p. 90) o References to Tables 4B and 5B for selecting recommended strains for routine QC (p. 90) o Instructions for QC when using a commercial test system (p. 90) o -

Added the following veterinary-specific breakpoints: Ampicillin MIC breakpoints with dosing regimen for cattle (p. 91) o

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VET08, 4th ed.

Overview of Changes (Continued) s e g n a h C f o w e i v r e v O

-

Added the following comments and/or footnotes: General comments on: o Reading disk diffusion plates and zone margins (p. 90) Antimicrobial agent dose used (if not listed) for each breakpoint evaluation (p. 90) Fluoroquinolones footnote indicating ciprofloxacin is not recommended for any veterinary o species because PK-PD analysis does not support its use (p. 91)  



Table 4A. Disk Diffusion QC Ranges for Nonfastidious Organisms (p. 96): Added new table with disk diffusion QC ranges for nonfastidious organisms organisms (formerly in Table 4) -

Added or changed QC ranges for: E. coli ATCC coli ATCC® 25922 o Doxycycline Minocycline Piperacillin Piperacillin-tazobactam S. aureus ATCC aureus ATCC® 25923 o Doxycycline Minocycline Piperacillin Piperacillin-tazobactam Pirlimycin o P. aeruginosa ATCC® 27853 Piperacillin Piperacillin-tazobactam    

    

 

-

-

-



Added footnote with information about gentamicin and streptomycin high-level aminoglycoside resistance (HLAR) tests for enterococci ticarcillin and Deleted ticarcillin

ticarcillin-clavulanate ticarcillin-clavulanate

Table 4B. Disk Diffusion QC Ranges for Fastidious Organisms (p. 98): Added new table with disk diffusion QC ranges for fastidious organisms, including: Streptococcus pneumoniae ATCC pneumoniae ATCC® 49619 (formerly in Table 4) o Mannheimia haemolytica haemolytica ATCC ATCC® 33396 (formerly in VET01-A4, Section 7.4.1) o o Histophilus somni somni ATCC ATCC® 700025 (formerly in Table 6) Actinobacillus pleuropneumoniae pleuropneumoniae ATCC ATCC® 27090 (formerly in Table 6) o -

-



Added piperacillin-tazobactam QC ranges for E. coli ATCC coli ATCC® 35218 to footnote

Added QC range for S. pneumoniae ATCC® 49619 for doxycycline Added table with disk diffusion testing conditions for clinical isolates and performance of QC (formerly in Table 7)

Table 4C. Disk Diffusion Reference Guide to QC Frequency (p. 100): Added new table

-



xvi

Table 4D. Disk Diffusion Troubleshooting Guide (p. 102): Added new table (formerly Appendix D1 in VET01-A4)


VET08, 4th ed.

Overview of Changes (Continued) 

Table 5A. MIC QC Ranges for Nonfastidious Organisms (p. 106): Added new table with MIC QC ranges for nonfastidious organisms (formerly in Table 5)


-

-

Added or changed QC ranges for: o S. aureus ATCC® 29213 Doxycycline Minocycline Piperacillin Piperacillin-tazobactam o E. faecalis ATCC faecalis ATCC® 29212 Doxycycline Minocycline Piperacillin Piperacillin-tazobactam o E. coli ATCC coli ATCC® 25922 Doxycycline Minocycline Piperacillin Piperacillin-tazobactam P. aeruginosa ATCC® 27853 o Piperacillin Piperacillin-tazobactam    

   

   

 

-

-

-



Added footnotes with QC information for: Erythromycin/clindamycin Erythromycin/clindamycin combination well for detecting inducible clindamycin resistance o o Gentamicin and streptomycin HLAR tests for enterococci o Agents (sulfisoxazole and trimethoprim-sulfamethoxazole) that may be affected by excess levels of thymidine and thymine Vancomycin screen test for enterococci o Deleted ticarcillin ticarcillin and

ticarcillin-clavulanate ticarcillin-clavulanate

Table 5B. MIC QC Ranges for Fastidious Organisms (Broth Dilution Methods) (p. 108): Added new table with MIC QC ranges for fastidious organisms, including: Streptococcus pneumoniae ATCC pneumoniae ATCC® 49619 (formerly in Table 5) o o Mannheimia haemolytica haemolytica ATCC ATCC® 33396 (formerly in VET01-A4, Section 12.1) Histophilus somni somni ATCC ATCC® 700025 (formerly in Table 6) o Actinobacillus pleuropneumoniae pleuropneumoniae ATCC ATCC® 27090 (formerly in Table 6) o -

-



Added piperacillin-tazobactam QC ranges for E. coli ATCC coli ATCC® 35218 to footnote

Added QC range for S. pneumoniae ATCC® 49619 for doxycycline Added table with MIC testing conditions for clinical isolates and performance of QC (formerly in Table 7)

Table 5E. MIC Reference Guide to QC Frequency (p. 114): Added new table -

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VET08, 4th ed.




Table 5F. MIC Troubleshooting Guide (p. 116): Added new table (formerly Appendix D2 in VET01-A4)

-



Table 6. Solvents and Diluents for Preparing Stock Solutions of Antimicrobial Agents (p. 120): Added common antimicrobial agents for which water solvent and diluent are needed for preparing stock solutions: Aminoglycosides Aminoglycosides (amikacin, gentamicin, kanamycin) o Piperacillin o Tazobactam o Tetracyclines (doxycycline, minocycline, tetracycline) o o Vancomycin -

ticarcillin Deleted ticarcillin



Table 7A. Disk Diffusion Tests for Extended-Spectrum -Lactamases in Klebsiella in Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia Escherichia coli, and coli, and Proteus Proteus mirabilis mirabilis (p. 122): Updated recommendations for test interpretation and reporting -



Table 7B. Broth Microdilution Tests for Extended-Spectrum -Lactamases in Klebsiella pneumoniae, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia Escherichia coli, and coli, and Proteus Proteus mirabilis mirabilis (p. (p. 124): Updated recommendations for test interpretation and reporting -



Table 7C. Test for Detection of β-Lactamase Production in Staphylococcus in Staphylococcus spp. (p. 126): Updated to include complete instructions for disk diffusion (penicillin zone-edge test) and nitrocefin-based test



Table 7D. Disk Diffusion Test for Prediction of mecA mecA-Mediated -Mediated Resistance in Staphylococci (p. 130): Added S. schleiferi to schleiferi to S. pseudintermedius pseudintermedius organism organism group -



Table 7E. Vancomycin Agar Screen for Staphylococcus for Staphylococcus aureus and Enterococcus and Enterococcus spp. (p. 132): Combined vancomycin agar screen for Enterococcus Enterococcus spp. (formerly in Table 9I) with the vancomycin agar screen for S. aureus in aureus in Table 7E -

-



Updated footnote to refer to VET01, 1 Subchapter 7.2.2 for description of methods, testing issues, and reporting recommendations

Added additional testing and reporting of: S. aureus that grow on brain heart infusion (BHI)–vancomycin screening agar o o Enterococcus spp. that grow on BHI-vancomycin screening agar Deleted resistance resistance screening for oxacillin resistance in S. aureus, which was previously combined with screening for reduced susceptibility to vancomycin in S. aureus

Table 7F. Test for Detection of Inducible Clindamycin Resistance in Staphylococcus Staphylococcus spp., Streptococcus spp. Streptococcus spp. -Hemolytic Group, and Streptococcus and Streptococcus pneumoniae pneumoniae (p. (p. 134): Updated to include complete instructions for disk diffusion (D-zone test) and broth microdilution Separated instructions for testing staphylococci and streptococci Added comment to consider including with antimicrobial susceptibility testing report -

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VET08, 4th ed.


Table 7G. Test for Detection of High-Level Aminoglycoside Resistance in Enterococcus spp. (Includes Disk Diffusion) (p. 136): Combined disk diffusion and dilution tests for detection of HLAR in Enterococcus spp. (formerly in Tables 9H and 9I, respectively) in Table 7G Added additional testing and reporting recommendations



Appendix A. Suggestions for Confirming Resistant, Intermediate, or Nonsusceptible Antimicrobial Susceptibility Test Results and Organism Identification (p. 138): Added new appendix for veterinary application -



Appendix B. Intrinsic Resistance (p. 142): Added new appendix for veterinary application



Appendix C. QC Strains for Antimicrobial Susceptibility Tests (p. 148): Added new appendix for veterinary application -



Appendix D. Epidemiological Cutoff Values (p. 152): Added new appendix for veterinary application

-



Appendix E. CLSI Veterinary-Specific Breakpoint Additions/Revisions to VET01 Supplements Since 1999 (p. 154): Added comprehensive list of all CLSI veterinary-specific breakpoints -



Glossary I. Antimicrobial Class and Subclass Designations, Antimicrobial Agents, and Antimicrobial Resistance Mechanisms (p. 160): Added ribosomal protection to the antimicrobial resistance mechanisms of: Lincosamides o Phenicols o Pleuromutilins o o Streptogramins Tetracyclines o -

Deleted: o o

o o o o

o

Ticarcillin-clavulanate Ticarcillin-clavulanate from antimicrobial class -lactam combination agents Cephems in the antimicrobial subclass cephalosporins with anti-MRSA activity (ceftaroline and ceftobiprole) Linezolid and the antimicrobial antim icrobial class oxazolidinones Ticarcillin from antimicrobial class penicillins Mupirocin and the antimicrobial class pseudomonic acid Streptogramins A, except virginiamycin M, streptogramins B except virginiamycin S, and streptogramins combinations except virginiamycin Fosfomycin from antimicrobial agents listed as antimicrobial class “Others”

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VET08, 4th ed.




Glossary II. Abbreviations Commonly Used for Antimicrobial Agents Incorporated Into Disks or Susceptibility Panels (p. 164): Added antimicrobial agents and abbreviations for: Cephalexin o o Doxycycline Piperacillin o Piperacillin-tazobactam o Tobramycin o -

-

Added abbreviations for: Ceftazidime o Clarithromycin o Trimethoprim-sulfamethoxazole o Deleted: o o



Ticarcillin-clavulanate Ticarcillin

Glossary III. List of Identical Abbreviations Used for More Than One Antimicrobial Agent in US Diagnostic Products (p. 166): Added new glossary

NOTE: The content of this document is supported by the CLSI consensus process and does not necessarily reflect the views of any single individual or organization.

xx


VET08, 4th ed.

Summary of CLSI Processes for Establishing Breakpoints and Quality Control Ranges The Clinical and Laboratory Standards Institute (CLSI) is an international, voluntary, not-for-profit, interdisciplinary, standards-developing, standards-developing, and educational organization accredited by the American National Standards Institute that develops and promotes the use of consensus-developed standards and guidelines within the health care community. These consensus standards and guidelines are developed in an open and consensus-seeking forum to cover critical areas of diagnostic testing and patient health care. CLSI is open to anyone or any organization that has an interest in diagnostic testing and patient care. Information about CLSI is found at www.clsi.org. The CLSI Subcommittee on Veterinary Antimicrobial Susceptibility Testing reviews reviews data from a variety of sources and studies (eg, in vitro, pharmacokinetics-pharmacodynamics, and clinical studies) to establish antimicrobial susceptibility susceptibility test methods, breakpoints, and QC parameters. The details of the data necessary to establish breakpoints, QC parameters, and how the data are presented for evaluation are described in CLSI document VET02. 7 The Subcommittee’s goal is to establish veterinary-specific breakpoints to decrease reliance on human medical breakpoints. However, human medical breakpoints are still listed in VET08 Table 2 series, identified with gray-shaded text, allowing comparison of veterinary-specific and human medical breakpoints. Human breakpoints are occasionally necessary to provide zones of inhibition for some categories and a breakpoint for laboratories to consider when there are no veterinary breakpoints available for some antimicrobial agents and organisms for all animal species. Over time, a microorganism’s susceptibility to an antimicrobial agent may decrease, resulting in a lack of clinical efficacy and/or safety. In addition, microbiological methods and QC parameters may be refined to ensure more accurate and better performance of susceptibility test methods. Because of these types of changes, CLSI continually monitors and updates information in its documents. Although CLSI standards and guidelines are developed using the most current information available at the time, the field of science and medicine is always changing; therefore, standards and guidelines should be used in conjunction with clinical judgment, current knowledge, and clinically relevant laboratory test results to guide patient treatment. Additional information, information, updates, and changes in this document are found in the meeting summary minutes of the Subcommittee on Veterinary Antimicrobial Susceptibility Testing at www.clsi.org.

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VET08, 4th ed.

CLSI Reference Methods vs Commercial Methods and CLSI vs Regulatory Authority It is important for users of VET01 1 and VET08 to recognize that the standard methods described in CLSI documents are reference methods. These methods may be used for routine antimicrobial susceptibility testing of patient isolates. CLSI recognizes that commercial susceptibility testing devices are commonly used by veterinary diagnostic laboratories. Commercial testing devices used in veterinary medicine may not have demonstrated that test results from such systems are substantially equivalent to those generated using reference methods. For example, the US Food and Drug Administration does not have preapproval or regulatory clearance requirements for use of commercial testing devices for veterinary isolates. Manufacturers of commercial testing devices are expected to validate their methods against CLSI reference methods, but CLSI does not evaluate these data. Laboratories should follow follow the manufacturer’s instructions for quality assurance and quality control testing. The laboratory is responsible for ensuring that the performance of commercial test systems has been validated against the reference method(s). Currently, there are no regulations that apply to veterinary laboratories regarding susceptibility testing. Veterinary-specific breakpoints are not set by regulatory agencies but have been developed and approved solely by the CLSI Subcommittee on Veterinary Antimicrobial Susceptibility Testing. The guidelines used by CLSI to evaluate data and determine breakpoints are outlined in CLSI document VET02. 7 CLSI proactively evaluates the need for changing breakpoints. Following a decision by CLSI to change an existing clinical breakpoint, a delay of one or more years may be needed if a breakpoint and interpretive category change is to be implemented by a device manufacturer. Each laboratory should check with the manufacturer of its commercial susceptibility testing testing device for additional information on the breakpoints and interpretive categories used in its system’s software. Following discussions with appropriate stakeholders (eg, veterinarians, infectious diseases practitioners, clinical pharmacologists, and antimicrobial stewardship teams, if available), newly approved or revised breakpoints may be implemented by veterinary diagnostic laboratories. If approved by CLSI, new or revised breakpoints will be published in VET08. VET08.

xxii


VET08, 4th ed.

CLSI Veterinary-Specific Breakpoint Additions/Revisions Since 2015* Antimicrobial Agent Ampicillin

Table 2A

Organism(s) Escherichia coli

Animal Species Cats

Cats

Body Site SST, UTI UTI

Cefovecin

2A

E. coli

Sponsor (January 2018)

Ampicillin

2A

E. coli

Cattle

Metritis

GWG (January 2018)

Cefazolin

2A

E. coli Klebsiella pneumoniae pneumoniae Proteus mirabilis mirabilis E. coli P. mirabilis mirabilis E. coli K. pneumoniae P. mirabilis mirabilis E. coli

Dogs

UTI

GWG (January 2017)

Cefovecin

2A

Dogs

UTI


Cefpodoxime

2A

Dogs

UTI

GWG (January 2017)

Cephalexin

2A

Dogs

SST

GWG (June 2015)

Cephalexin

2A

Dogs

UTI

GWG (January 2017)

2A

E. coli K. pneumoniae P. mirabilis mirabilis Enterobacteriaceae

Piperacillintazobactam Doxycycline

Dogs

GWG (June 2015)

2A

E. coli

Horses

Enrofloxacin

2A

E. coli

Horses

Minocycline

2A

E. coli

Horses

Piperacillintazobactam Enrofloxacin

2B

Pseudomonas aeruginosa aeruginosa

Dogs

2B

P. aeruginosa

Horses

Ampicillin

2C

Staphylococcus spp.

Cats

Cefovecin

2C

Dogs


Cephalexin

2C

Dogs

SST

GWG (June 2015)

Minocycline

2C

Staphylococcus pseudintermedius Staphylococcus aureus S. pseudintermedius S. pseudintermedius S. pseudintermedius

SST, UTI Resp, SST Resp, SST Resp, SST SST, UTI Resp, SST SST, UTI SST

Dogs

SST

GWG (June 2015)

Piperacillintazobactam

2C

Staphylococcus spp.

Dogs

SST, UTI

GWG (June 2015)

Doxycycline

2C

S. aureus

Horses

GWG (January 2017)

Enrofloxacin

2C

S. aureus

Horses

Minocycline

2C

S. aureus

Horses

Ampicillin

2D

Streptococcus spp.

Cats

Resp, SST Resp, SST Resp, SST SST, UTI

Data Source Presentation GWG (January 2018)

GWG (January 2017) GWG (January 2017) GWG (January 2018) GWG (June 2015) GWG (January 2017) GWG (January 2018)

GWG (January 2017) GWG (January 2017) GWG (January 2018)

xxiii


VET08, 4th ed.

CLSI Veterinary-Specific Breakpoint Additions/Revisions Since 2015* (Continued) Antimicrobial Agent Cefovecin

Table 2D

Cephalexin

2D

Doxycycline

2D

Enrofloxacin

2D

Minocycline

2D

Organism(s) Streptococcus -hemolytic group Streptococcus -hemolytic group Streptococcus equi subsp. equi and equi and zooepidemicus zooepidemicus S. equi subsp. equi and equi and zooepidemicus Streptococcus spp.

Animal Species Dogs

Body Site SST

Data Source Presentation Sponsor (January 2018)

Dogs

SST

GWG (June 2015)

Horses

GWG (January 2017)

Cattle

Resp, SST Resp, SST Resp, SST Resp

Ampicillin

2G

Mannheimia haemolytica haemolytica

Danofloxacin

2G

M. haemolytica haemolytica

Cattle

Resp

Ampicillin

2H

Pasteurella multocida multocida

Cats

Cefovecin

2H

P. multocida multocida

Cats

Ampicillin

2H


Cattle

SST, UTI SST, UTI Resp

Danofloxacin

2H


Cattle

Resp

Ampicillin

2J

Histophilus somni somni

Cattle

Resp

Horses Horses

GWG (January 2017) GWG (January 2017) GWG (January 2018) Sponsor (January 2016, I and R breakpoints) GWG (January 2018) Sponsor (January 2018) GWG (January 2018) Sponsor (January 2016, I and R breakpoints) GWG (January 2018)

Abbreviations: GWG, Generic Drug Working Group; I, intermediate; R, resistant; resp, respiratory; SST, skin and soft tissue; UTI, urinary tract infection. *

For breakpoint additions/revisions since 1999, see Appendix E. Past editions of the standard (with breakpoint tables included) and supplement include: M31-A (June 1999), M31-A2 (May 2002), M31-S1 ( May 2004), VET01-A3 (February 2008), VET01-S2 (July 2013), and VET01S, 3rd ed. (June 2015).

xxiv


VET08, 4th ed.

Subcommittee on Veterinary Antimicrobial Susceptibility Testing Mission Statement and Responsibilities Mission Statement:

Develop and promote performance standards, breakpoints, and interpretive categories for antimicrobial susceptibility susceptibility testing of bacteria isolated from animals.

in vitro

Responsibilities:

The Subcommittee on Veterinary Antimicrobial Susceptibility Susceptibility Testing is composed of representatives from the professions, government, and industry, including microbiology laboratories, government agencies, health care providers and educators, and pharmaceutical and diagnostic microbiology industries. Using the CLSI voluntary consensus process, the subcommittee develops standards that promote accurate antimicrobial susceptibility testing and appropriate reporting. Responsibilities of the Subcommittee on Veterinary Antimicrobial Susceptibility Testing include: 

Developing standard reference methods for antimicrobial susceptibility susceptibility tests



Providing quality control parameters for standard test methods







Establishing breakpoints and interpretive categories for the results of standard antimicrobial susceptibility tests performed on veterinary pathogens Providing suggestions for testing and reporting strategies that are clinically relevant and cost-effective Continually refining standards through development of new or revised methods, breakpoints, interpretive categories, and quality control parameters



Educating users through multimedia communication of standards and guidelines



Fostering a dialogue with users of these methods and those who apply them

The ultimate purpose of the subcommittee’s mission is to provide useful information to enable veterinary diagnostic laboratories to assist the clinician in the selection of appropriate antimicrobial therapy for patient care. The standards and guidelines are meant to be comprehensive and to include all antimicrobial agents for which the data meet established CLSI guidelines. The values that guide this mission are quality, accuracy, fairness, timeliness, teamwork, consensus, and trust.

xxv


VET08, 4th ed.

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xxvi


For Use With VET01

VET08, 4th ed.

Instructions for Use of Tables These instructions apply to: 



Table 1: suggested groupings of antimicrobial agents that should be considered for routine testing and reporting by microbiology laboratories. Placement of antimicrobial agents in Table 1 is either based on approval by relevant relevant regulatory organizations organizations or on use consistent consistent with good clinical practice. Tables 2A through 2J: tables for each organism group that contain: Recommended testing conditions Routine QC recommendations (also see Chapter 8 in VET01 1) General comments for testing the organism group and specific comments for testing particular agent/organism combinations Suggested agents that should be considered for routine testing and reporting by veterinary microbiology laboratories, as specified in Table 1 (test/report groups A, B, C, D) Zone diameter and minimal inhibitory concentration (MIC) breakpoints

  







Tables 3 through 5: tables for acceptable QC organisms, sources, and acceptable result ranges



Table 6: table of solvents and diluents for preparing stock solutions of antimicrobial agents



Tables 7A through 7G: tables describing tests to detect particular resistance types in specific organisms or organism groups (also see Chapter 7 in VET01 1).

I.

Selecting Antimicrobial Agents for Testing and Reporting

A.

Selecting the most appropriate antimicrobial agents to test and report is a decision best made by each laboratory in consultation with veterinarians, infectious diseases practitioners, clinical pharmacologists, and antimicrobial antimicrobial stewardship stewardship teams, if available. The recommendations recommendations for each each organism group include antimicrobial agents that show acceptable in vitro vitro test performance. Considerations in the assignment of antimicrobial agents to specific test/report groups include clinical efficacy, prevalence of resistance, minimizing emergence of resistance, cost, regulatory agency–approved clinical indications for use, and current consensus recommendations for firstchoice and alternative agents. Tests of selected agents may be useful for infection control and/or monitoring purposes.

B.

Antimicrobial agents listed together in a single box are agents for which interpretive categories (susceptible, intermediate, or resistant) and clinical efficacy are similar. Within each box, an “or” between agents indicates agents for which cross-resistance and cross-susceptibility cross-susceptibility are nearly complete. Results from one agent connected by an “or” can be used to predict results for the other agent. For example, Enterobacteriacea example, Enterobacteriaceaee susceptible to ampicillin can be considered susceptible to amoxicillin. The results obtained from testing ampicillin could be reported along with a comment that the isolate is also susceptible to amoxicillin. For drugs connected with an “or,” combined major and very major errors are fewer than 3%, and minor errors are fewer than 10%, based on a large population of bacteria tested (see CLSI documents VET02 7 and M238 for description of error types). “Or” is also used for comparable agents when tested against organisms for which “susceptible-only” breakpoints are provided (eg, ampicillin or amoxicillin with Streptococcus canis). canis). When no “or” connects agents within a box, testing of one agent cannot be used to predict results for another, owing either to discrepancies or insufficient data.

©

Clinical and Laboratory Standards Institute. All rights reserved.

1


For Use With VET01

VET08, 4th ed.

C.

Test/Report Groups The antimicrobial agents listed in groups A, B, C, and D in Table 1 include recommendations for appropriate reporting. Antimicrobial agents listed in groups A, B, and C in Table 1 are the agents that have been approved by regulatory agencies or authorities for diseases in the indicated host animal. Only group A designations are restated in the Table 2 series that lists the breakpoints and interpretive categories for species-specific breakpoints in each organism group. To avoid misinterpretation, routine reports to veterinarians should include antimicrobial agents appropriate for therapeutic use. 1. Group A includes antimicrobial agents with veterinary-specific breakpoints and interpretive categories that are considered appropriate for inclusion in a routine, primary testing panel for food and companion animals, as well as for routine reporting of results for the specified organism groups. The recommended hierarchy for reporting is to first report group A agents over those using human medical breakpoints, because these compounds have demonstrated an acceptable level of correlation between in vitro susceptibility test results and clinical outcome. 2. Group B includes antimicrobial agents that use human medical breakpoints and interpretive categories and are next in the hierarchy to report. These agents may perform adequately, but outcome for many veterinary applications has not been demonstrated. The veterinary laboratory may use its discretion to decide whether to selectively report the results from testing these agents. 3. Group C includes antimicrobial agents that are regulatory agency–approved for use in the specific animal species. Although QC data are available for these agents, they do not have veterinary- or human-specific CLSI-approved breakpoints and interpretive categories. These agents may be approved for use in other animal species and have veterinary-specific breakpoints in those animals. However, reporting interpretive categories determined by breakpoints set for a particular animal species is not recommended for application to other animal species because there are differences in dosages and pharmacokinetics between animals and people and between animal species. Thus, these agents should be reported selectively before extra-label use agents (group (group D) but after agents in group group B. 4. Group D includes agents that are not approved but may be used in an extra-label manner per the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) guidelines 9 in the United States and per similar regulations in other countries for the listed animal. These supplemental agents may be selectively tested and selectively reported. Group D agents may be included in testing for monitoring antimicrobial resistance patterns or for surveillance programs (eg, oxacillin, vancomycin, vancomycin, carbapenems). See VET01,1 Subchapter 2.3 for additional information on routine reporting.

D.

Selective Reporting Each laboratory should decide which antimicrobial agents in Table 1 to report routinely (group A) and which might be reported only selectively. Results for antimicrobial agents tested but not reported routinely should be available on request, or they may be reported for selected specimen types. Agents in groups A, B, and C may be reported routinely or selectively, as outlined in VET01, 1 Subchapter 2.4. However, some group A, B, and C agents are not approved by regulatory agencies or authorities in some countries, and others may be illegal or prohibited in some countries. For example, in the United States, AMDUCA prohibits the use of fluoroquinolones fluoroquinolones and glycopeptides

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for extra-label use in food animals. 10 The laboratory client is responsible for ensuring that compounds are used appropriately for host categories for each animal (eg, lactating cows, calves) in accordance with the approved indication. The veterinarian assumes all responsibility for efficacy, safety, and residue avoidance when antimicrobial agents are used in an extra-label manner.

When unexpected resistance is confirmed, it should be reported (eg, r esistance to a secondary agent but susceptibility susceptibility to a primary agent, such as a P. aeruginosa isolate resistant to amikacin but susceptible to tobramycin; as such, both drugs should be reported). See Appendix A for unusual phenotype resistance. In addition, each laboratory should develop a protocol to cover isolates that are confirmed as resistant to all antimicrobial agents on its routine test panel. This protocol should include options for testing additional agents in-house or sending the isolate to a referral laboratory. For additional information and examples of guidelines for selective reporting, see VET01, 1 Subchapter 2.4. Selective reporting for pathogens with intrinsic resistance to antimicrobial agents (see Appendix B) is discussed in VET01, 1 Subchapter 2.4.4. II.

Breakpoints and Interpretive Category Definitions

A.

Breakpoint – minimal inhibitory concentration (MIC) or zone diameter value used to categorize an organism as susceptible, intermediate, nonsusceptible, or resistant; NOTE 1: MIC or zone diameter values generated by a susceptibility test can be interpreted based upon established breakpoints; NOTE 2: Because breakpoints are based on pharmacologically and clinically rich datasets using in vitro and in vivo data, they are considered to be robust predictors of likely clinical outcome; NOTE 3: Also known as “clinical breakpoint”; NOTE 4: See interpretive category.

B.

Interpretive category – category derived from microbiology characteristics, pharmacokinetic pharmacodynamic parameters, and clinical outcome data, when available; NOTE 1: MIC or zone diameter values generated by a susceptibility test can be interpreted based upon established breakpoints; NOTE 2: See breakpoint. EXAMPLE: Breakpoints* Interpretive Category Susceptible Intermediate Resistant Nonsusceptible

MIC, µg/mL 4 8–16  32 >4

Zone Diameter, mm  20 15–19  14 < 20

*

Formerly “interpretive criteria.”

MIC or zone diameter value breakpoints or interpretive categories are established per CLSI document VET02 7 (or CLSI document M23 8 for human medical breakpoints) for categories of susceptible, intermediate, and resistant (and nonsusceptible, nonsusceptible, when appropriate). 

©

Susceptible (S) – a category defined by a breakpoint that implies that isolates with an MIC at or below or zone diameters at or above the susceptible breakpoint are inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat the site of infection is used, resulting in likely clinical efficacy.


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C.



Intermediate (I) – a category defined by a breakpoint that includes isolates with MICs or zone diameters within the intermediate range that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates; NOTE: The intermediate category implies clinical efficacy in body sites for which the drugs are physiologically concentrated or when a higher than than normal dosage of a drug can be used. This category also includes a buffer zone, which should prevent small, uncontrolled, technical factors from causing major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins. margins.



Resistant (R) – (R) – a category defined by a breakpoint that implies that isolates with an MIC at or above or zone diameters at or below the resistant breakpoint are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and/or that demonstrate MICs or zone diameters that fall in the range in which specific microbial resistance mechanisms are likely, and clinical efficacy of the agent against isolates has not been reliably shown in isolates with similar phenotypes.



Nonsusceptible (NS) – a category used for isolates for which only a susceptible breakpoint is designated because of the absence or rare occurrence of resistant strains. Isolates for which the antimicrobial agent MICs are above or zone diameters are below the value indicated for the susceptible breakpoint should be reported as nonsusceptible; NOTE 1: An isolate that is interpreted as nonsusceptible does not necessarily mean that the isolate has a resistance mechanism. It is possible that isolates with MICs above the susceptible breakpoint that lack resistance mechanisms may be encountered within the wild-type distribution subsequent subsequent to the time the susceptible-only breakpoint was set; NOTE 2: The term “nonsusceptible” “nonsusceptible” should not be used used when describing an organism/drug organism/drug category with intermediate and resistant resistant interpretive interpretive categories. Isolates that are in the categories of “intermediate” or “resistant” could be called “not susceptible” rather than “nonsusceptible.”

Example of Breakpoints and Interpretive Categories as Used in Table 2

Interpretive Categories and Zone Diameter Breakpoints, nearest whole mm Antimicrobial Agent

Interpretive Categories and MIC Breakpoints, µg/mL

Disk Content

S

I

R

S

I

R

X

30 μg

 20

15–19

 14

4

8–16

 32

Y

–

–

–

–

1

2

4

Z

10 μg

 16

–

–

1

–

–

For antimicrobial agent X with breakpoints in the table above, the susceptible breakpoint is ≤ 4 µg/mL or ≥ 20 mm and the resistant breakpoint is ≥ 32 µg/mL or ≤ 14 mm. For some antimicrobial agents (eg, antimicrobial agent Y), only MIC breakpoints may be available. For these agents, the disk diffusion zone diameters do not correlate with MIC values. Technical issues may also preclude the use of the disk diffusion method for some agents. For some antimicrobial agents (eg, antimicrobial agent Z) only a “susceptible” category exists. For these agents, the absence or rare occurrence of resistant strains precludes defining any results categories other than “susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility susceptibility test results should be confirmed (see Appendix A).

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In examples Y and Z, a dash mark (–) indicates a disk is not available or that breakpoints are not applicable. III.

Reporting Results

A.

Organisms Included in Table 2 The MIC values determined as described in VET01 1 may be reported directly to clinicians for patient care purposes. However, it is essential that an interpretive category result (S, I, or R) also be provided routinely to facilitate understanding of the MIC report by clinicians. Zone diameter measurements without an interpretive category should not be reported. Recommended interpretive categories for various MIC and zone diameter values are included in tables for each organism group and are based on the evaluation of data as described in CLSI document VET02 7 (or CLSI document M238 for human medical breakpoints). Laboratories should only report results for agents listed in Table 2 specific to the organism being tested. It is not appropriate to apply disk diffusion or MIC breakpoints borrowed from a table in which the organism is not listed. There may be rare cases for which an agent may be appropriate for an isolate but for which there are no CLSI breakpoints (eg, colistin). In these cases, the prescribing information document document for the agent should should be consulted. For more information on reporting epidemiological cutoff values in the medical laboratory, see Appendix D and CLSI document M100, 5 Appendix G.

B.

Organisms Excluded From Table 2 For some organism groups excluded from Tables 2A through 2J, CLSI document VET06 6 provides suggestions for standardized methods for susceptibility testing, including information about antimicrobial agent selection, interpretation, and QC. The organism groups covered in that guideline are aerobic actinomycetes; anaerobic bacteria; Bacillus Bacillus spp. (not B. anthracis); anthracis); Campylobacter jejuni/coli; Corynebacterium spp. (including C. diphtheriae) diphtheriae ) and coryneforms; Erysipeloth Erysipelothrix rix rhusiopath rhusiopathiae; iae; Helicobacter pylori; Listeria spp.; spp.; Melissococcus plutonius ; Moraxella spp. (including M. bovis, M. ovis, and M. bovoculi); bovoculi); rapidly growing mycobacteria; Paenibacillus larvae; Pasteurella spp., Pasteurella spp., other than P. multocida; Rhodococcus multocida; Rhodococcus equi; Trueperella pyogenes; and Gallibacterium and Gallibacterium anatis. For guidance on additional organisms, see CLSI documents 2 M02, M07,4 and M45.11 For organisms other than those in the groups mentioned above, studies are not yet adequate to develop reproducible, definitive standards to interpret results. These organisms may need different media or different incubation atmospheres, or they may show marked strain-to-strain variation in growth rate. For these microorganisms, consultation with an infectious diseases specialist is recommended for guidance in determining the need for susceptibility testing and in results interpretation. Published reports in the medical literature and current consensus recommendations for therapy of uncommon microorganisms may preclude the need for testing. If necessary, a dilution method usually is the most appropriate testing method, and this may necessitate submitting the organism to a referral laboratory. Clinicians should be informed of the limitations of results and advised to interpret results with caution.

C.

Cumulative Antibiograms Policies regarding the generation of cumulative antibiograms should be developed together with the infectious diseases practitioners, clinical pharmacologists, and antimicrobial stewardship teams, if available. In most circumstances, the percentage of susceptible and intermediate results should

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not be combined into the same statistics. See CLSI document M39 12 for instructions on generating cumulative antibiograms. IV.

Therapy-Related Comments

Some of the comments in the tables relate to therapy concerns. These are denoted with an Rx symbol. It may be appropriate to include some of these comments (or modifications thereof) on the patient report. An example would would be inclusion inclusion of a comment when ampicillin or penicillin is being reported for systemic enterococcal infections. Cases of uncomplicated urinary tract infections (UTIs) may be treated with -lactams such as ampicillin or penicillin, in which case this therapy would be successful even when resistance is documented. 13 However, the inclusion of a comment would be useful for the veterinarian on Enterococcus susceptibility Enterococcus susceptibility reports from blood cultures indicating that “combination therapy with ampicillin, penicillin, or vancomycin (for susceptible strains only), plus an aminoglycoside, is usually indicated for serious enterococcal infections, such as bacteremia, unless high-level resistance to both gentamicin and streptomycin is documented; such combinations are predicted to result in synergistic killing of the Enterococcus. For Enterococcus. For strains with low-level penicillin or ampicillin resistance when combination therapy with a β-lactam is being considered, also see additional testing and reporting information in Table 7G.” Antimicrobial dosage regimens often vary widely among practitioners and institutions. In some cases, the MIC breakpoints rely on pharmacokinetic-pharmacodynamic data, using specific veterinary dosage regimens. In cases in which specific dosage regimens are important for properly applying breakpoints, the dosage regimen is listed. These dosage regimen comments are not generally intended for use on individual patient reports. V.

Confirmation of Patient Results

Multiple test parameters are monitored by following the QC recommendations described in VET01.1 However, acceptable results derived from testing QC strains do not guarantee accurate results when testing patient isolates. It is important to review all results obtained from all drugs tested on a patient’s isolate before reporting the results. This review should include but not be limited to ensuring that 1) the antimicrobial susceptibility test results are consistent with the identification of the isolate; 2) the results from individual agents within a specific drug class follow the established hierarchy of activity rules; and 3) the isolate is susceptible to those agents for which resistance has not been documented (eg, vancomycin and Streptococcus spp.) and for which only “susceptible” breakpoints exist in VET08. Unusual or inconsistent results should be confirmed by rechecking various testing parameters detailed in Appendix A. Each laboratory must develop its own policies for confirming unusual or inconsistent antimicrobial susceptibility test results. The list provided in Appendix A emphasizes results that are most likely to affect patient care. VI.

Development of Resistance and Testing of Repeat Isolates

Isolates that are initially susceptible may become intermediate or resistant after initiation of therapy. Therefore, subsequent isolates of the same species from a similar body site should be tested in order to detect resistance that may have developed. Development of resistance can occur within as little as three to four days and has been noted most frequently in Enterobacter, Citrobacter, and Citrobacter, and Serratia spp. with third-generation cephalosporins; in P. aeruginosa with aeruginosa with all antimicrobial agents; and in staphylococci with fluoroquinolones. For S. aureus, vancomycin-susceptible aureus, vancomycin-susceptible isolates may become vancomycin intermediate intermediate during the course of prolonged prolonged therapy.

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In certain circumstances, the decision to perform susceptibility tests on subsequent isolates necessitates knowledge of the specific situation and the severity of the patient’s condition (eg, an isolate of P. aeruginosa aeruginosa from a blood culture on an oncology-immunocompromised dog or methicillin-resistant S. aureus [MRSA] aureus [MRSA] from a patient with bacteremia from a nonhealing wound). Laboratory guidelines on when to perform susceptibility testing on repeat isolates should be determined after consultation with the infectious diseases expert (eg, a veterinary microbiologist or clinical pharmacologist). VII.

Warning

Some of the comments in the tables relate to misleading results that can occur when certain antimicrobial agents are tested and reported as susceptible against specific organisms. These are denoted with the word “Warning.” Antimicrobial Agents That Must Not Be Location Organism Reported as Susceptible “Warning”: The following antimicrobial agent/organism combinations may appear active in vitro but vitro but are not effective clinically and must not be reported as susceptible. Table 2A Salmonella spp., Salmonella spp., Shigella spp. 1st- and 2nd-generation cephalosporins, cephamycins, and aminoglycosides Table 2E Enterococcus spp. Aminoglycosides Aminoglycosides (except for high-level resistance testing), cephalosporins, clindamycin, and trimethoprimsulfamethoxazole VIII.

Routine, Supplemental, Supplemental, Screening, Surrogate Agent, Agent, and Equivalent Agent Agent Testing to Determine Susceptibility and Resistance to Antimicrobial Agents

The testing categories are defined as follows: 



Routine test: disk diffusion or broth or agar dilution MIC tests for routine clinical testing Supplemental (not routine) test: test that detects susceptibility or resistance to a drug or drug class by method other than routine disk diffusion or broth or agar dilution MIC - Supplemental tests do not need additional tests to confirm susceptibility or resistance.

- Some supplemental tests identify a specific resistance mechanism and may be required or optional for reporting clinical results. 



©

Screening test: test that provides presumptive results; additional testing typically only needed for a specific result (eg, only if screen is positive) Surrogate agent test: test performed with an agent that replaces a test performed with the antimicrobial agent of interest and is used when the agent of interest cannot be tested due to availability or performance issues (eg, surrogate agent performs better than the agent of interest)


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

Equivalent agent test: test performed with an agent that predicts results of closely related agents of the same class and increases efficiency by limiting testing of multiple closely related agents. For example, tetracycline is tested as an equivalent agent to predict efficacy of oxytetracycline and chlortetracycline. Equivalent agents are identified by: - Listing equivalent agents with an “or” in Tables 1 and 2. “Or” indicates cross-susceptibility and cross-resistance is nearly complete (very major error + error + major error < 3%; minor error < 10%) and only one agent needs to be tested.

-

Listing agents that are equivalent and results that can be deduced by testing the equivalent agent in a comment (see Tables 1 and 2).

The following tables include the tests that fall into the supplemental, screening, and surrogate agent test categories. Supplemental Tests – Required

Supplemental Test β-lactamase

β-lactamase

Inducible clindamycin resistance (inducible lincosamide resistance)



Organisms CoNS

Test Description Chromogenic cephalosporin

Required for: Isolates that test penicillin susceptible before reporting the isolate as penicillin susceptible



S. aureus

Chromogenic cephalosporin; penicillin disk diffusion zoneedge test

S. aureus CoNS Streptococcus pneumoniae Streptococcus spp. β-hemolytic group

Broth microdilution or disk diffusion with clindamycin and erythromycin tested together

Isolates that test penicillin susceptible before reporting the isolate as penicillin susceptible Isolates that test erythromycin resistant and clindamycin susceptible or intermediate before reporting the isolate as clindamycin susceptible

  



VET08 Table Location 7C

7C

7F

Abbreviation: CoNS, coagulase-negative staphylococci.

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Supplemental Tests – Optional Supplemental Test ESBL

   

Oxacillin salt agar



CarbaNP

 

mCIM with or without eCIM





Organisms E. coli K. pneumoniae Klebsiella oxytoca oxytoca P. mirabilis mirabilis

Test Description Broth microdilution or disk diffusion clavulanate inhibition test for ESBLs

S. aureus

Agar dilution; MHA with 4% NaCl and 6 µg/mL oxacillin

Enterobacteriaceae P. aeruginosa

Colorimetric Colorimetric assay for detecting carbapenem hydrolysis

Optional for: Isolates demonstrating reduced susceptibility to cephalosporins

Results that indicate presence or absence of ESBLs Detecting MRSA; see cefoxitin surrogate agent tests, which are preferred. Isolates demonstrating reduced susceptibility to carbapenems

Results that indicate presence or absence of certain certain carbapenem carbapenemases ases Disk diffusion for Isolates demonstrating mCIM only: Enterobacteriaceae detecting carbapenem reduced susceptibility to hydrolysis carbapenems and P. and P. aeruginosa (inactivation) Results that indicate presence or absence of eCIM add-on enables mCIM with eCIM: certain carbapenemases differentiation of Enterobacteriaceae Enterobacteriaceae metallo-β-lactamases only from serine carbapenemases in Enterobacteriaceae isolates that are mCIM positive mCIM positive

Table Location 7A, 7B

7D

M1005 Tables 3B and 3B-1

M1005 Table 3C

Abbreviations: eCIM, EDTA-modified carbapenem inactivation method; ESBL, extended-spectrum β-lactamase; mCIM, modified carbapenem inactivation method; MHA, Mueller-Hinton Agar; MRSA, methicillin-resistant Staphylococcus aureus.

Screening Tests Screening Test Vancomycin agar screen

HLAR by disk diffusion

Organisms  S. aureus  Enterococcus spp.

Test Description Agar dilution; BHI with 6 µg/mL vancomycin

Enterococcus spp.

Disk diffusion with gentamicin and streptomycin



When to Perform Confirmatory Test If screen positive

If screen inconclusive

Confirmatory Test Vancomycin MIC

Broth microdilution, agar dilution MIC

VET08 Table Location 7E

7G

Abbreviations: BHI, brain heart infusion; HLAR, high-level aminoglycoside resistance; MIC, minimal inhibitory concentration.

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Surrogate Agent Tests Surrogate Agent Cefazolin

Cefoxitin

Organisms  E. coli Klebsiella spp.  Klebsiella spp. mirabilis  P. mirabilis

 

 

Oxacillin



Test Description Broth microdilution or disk diffusion

S. aureus Staphylococcus lugdunensis CoNS Not for S. pseudintermedius or S. schleiferi

Broth microdilution (S. (S. aureus and aureus and S. lugdunensis only) lugdunensis only) or disk diffusion

S. pneumoniae

Disk diffusion

Results When used for therapy of uncomplicated UTIs, predicts results for the following oral antimicrobial agents: cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and loracarbef.

Cefpodoxime, cefdinir, and cefuroxime may be tested individually because some isolates may be susceptible to these agents while testing resistant to cefazolin. Predicts results for mecAmecAmediated oxacillin resistance NOTE: Some CoNS (non– S. S. epidermidis) epidermidis) strains (eg, from bovine mastitis) mastitis) for which the oxacillin MICs are 0.5–2 µg/mL lack mecA (see mecA (see Table 2C, comment [25]). Non– S. S. epidermidis isolates from serious infections with MICs in this range may be tested for mecA or mecA or for PBP2a. Isolates that test mecA or mecA or PBP2a negative should be reported as oxacillin susceptible. Predicts penicillin susceptibility if oxacillin zone is ≥ 20 mm. If oxacillin zone is ≤ 19 mm, penicillin MIC must be done.

VET08 Table Location 2A

2C, 7D

2D

Abbreviations: CoNS, coagulase-negative staphylococci; MIC, minimal inhibitory concentration; PBP2a, penicillin binding protein 2a; UTI, urinary tract infection. infection.

IX.

Quality Control

Recommendations for QC are included in various tables and appendixes. Culture collection numbers for organisms used for QC of antimicrobial susceptibility tests are included in Table 3. Acceptable ranges for QC strains are provided in Tables 4A and 4B for disk diffusion and Tables 5A through 5D for MIC testing. Guidance for QC frequency and modifications of antimicrobial susceptibility testing testing systems is found in Table 4C for disk diffusion and Table 5E for MIC testing. Guidance for troubleshooting out-of-range results is included in Table 4D for disk diffusion and Table 5F for MIC testing. Additional information is available in Appendix C (eg, QC organism characteristics, QC testing recommendations).

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Abbreviations and Acronyms

AMDUCA AST ATCC®a BHI CAMHB CCUG CFU CoNS CRBIP DMSO DNA DSM eCIM ECV EDTA ESBL gen GWG HLAR I ID IM IU IV JCM LHB mCIM MHA MHB MIC MRS MRSA NCTC NS NWT pH PBP2a PCR PD PK PK-PD QC R resp RNA S SC SST TSA

Animal Medicinal Drug Use Clarification Act of 1994 antimicrobial susceptibility testing American Type Culture Collection brain heart infusion cation-adjusted Mueller-Hinton broth Culture Collection, University of Göteborg, Sweden colony-forming unit(s) coagulase-negative coagulase-negative staphylococci Centre de Ressources Biologiques de l’Institut Pasteur dimethyl sulfoxide deoxyribonucleic acid Deutsche Sammlung von Mikroorganismen und Zellkulturen EDTA-modified carbapenem inactivation method epidemiological cutoff value ethylenediaminetetraaceticc acid ethylenediaminetetraaceti extended-spectrum -lactamase genital Generic Drug Working Group high-level aminoglycoside resistance intermediate identification intramuscularly international unit(s) intravenously Japan Collection of Microorganisms lysed horse blood modified carbapenem inactivation method Mueller-Hinton agar Mueller-Hinton broth minimal inhibitory concentration methicillin-resistant methicillin-resistant staphylococci methicillin-resistant Staphylococcus aureus National Collection of Type Cultures nonsusceptible non-wild-type negative logarithm of of hydrogen ion concentration concentration penicillin-binding penicillin-binding protein 2a polymerase chain reaction pharmacodynamic pharmacokinetic pharmacokinetic-pharmacodynamic quality control resistant respiratory ribonucleic acid susceptible subcutaneously skin and soft tissue tryptic soy agar

a

ATCC® is a registered trademark of the American Type Culture Collection.

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UTI VFM wds/absc WT

12

urinary tract infection veterinary fastidious medium wounds and/or abscesses wild-type

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References 1

CLSI. Performan CLSI. Performance ce Standards for Antimicrobi Antimicrobial al Disk and Dilution Dilution Susceptibility Susceptibility Tests for Bacteria Bacteria Isolated From Animals. Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; Institute; 2018.

2

CLSI. Performance CLSI. Performance Standards Standards for Antimicrobial Disk Susceptibility Susceptibility Tests. 13th ed. ed. CLSI standard M02. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

3

CLSI. M02 Disk Diffusion Reading Guide. Guide. 1st ed. CLSI quick guide M02QG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

4

CLSI. Methods CLSI. Methods for Dilution Dilution Antimicrobial Susceptibility Susceptibility Tests for Bacteria That Grow Aerobically. Aerobically. 11th ed. CLSI document M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

5

CLSI. Performan CLSI. Performance ce Standards for Antimicrobial Antimicrobial Susceptibility Susceptibility Testing . 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

6

CLSI. Methods CLSI. Methods for Antimicrobial Antimicrobial Susceptibility Susceptibility Testing of Infrequently Isolated or Fastidious Fastidious Bacteria Isolated From From Animals. 1st ed. CLSI supplement VET06. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.

7

CLSI. Development CLSI. Development of In Vitro Susceptibility Vitro Susceptibility Testing Criteria and Quality Control Parameters for Veterinary Antimicrobial Agents; Approved Guideline— Guideline—Third Third Edition Edition.. CLSI document VET02-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.

8

CLSI. Development CLSI. Development of In Vitro Susceptibility Testing Criteria and Quality Control Parameters. 5th ed. CLSI guideline M23. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

9

US Food and Drug Administration, US Department of Health and Human Services. Part 530—Extralabel Drug Use in Animals (Codified at 21 CFR §530); US Government Publishing Office; published published annually.

10

Payne MA, Baynes RE, Sundlof SE, Craigmill A, Webb AI, Riviere JE. Drugs prohibited from extralabel use in food animals. J animals. J Am Vet Med Assoc. Assoc. 1999;215(1):28-32.

11

CLSI. Methods CLSI. Methods for Antimicrobial Dilution Dilution and Disk Susceptibility Susceptibility Testing of Infrequently Infrequently Isolated or Fastidious Fastidious Bacteria . 3rd ed. CLSI guideline M45. Wayne, PA: Clinical and Laboratory Standards Institute; 2016.

12

CLSI. Analysis CLSI. Analysis and and Presentation Presentation of Cumulative Cumulative Antimicrobial Antimicrobial Susceptibility Susceptibility Test Data; Data; Approved Approved Guideline—Fourth Guideline—Fourth Edition . CLSI document M39-A4. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.

13

Arias CA, Murray BE. Enterococcu BE. Enterococcuss species, Streptococcus gallolyticus group, and Leuconosto and Leuconostocc species. In: Bennett JE, Dolin R, Blaser MJ. Mandell, MJ. Mandell, Douglas, Douglas, and Bennett’s Infectious Infectious Disease Disease Essentials Essentials.. Philadelphia, PA: Elsevier; 2017:283-284.

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s e c n e r e f e R

8 1 0 2 / 6 1 / 8 0 - N L 3 S 1 0 T E V n i m d A c i r e n e G N F 3 S 1 0 T E V n i m d A c i r e n e G - S 1 0 T E V I S L C

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C l i n i c a l a n d L a b o r a t o r y S t a n d a r d s I n s t i t u t e . A l l r i g h t s r e s e r v e d .

Table 1. (Continued) Cattlea Sulfonamides

Swine Gentamicin

s t n t i o r o p p k e a R e r y B l e v n — a i t c B m l e p u e H S u o d t , r s e G e v o T r y p r p a A - i m I r S P L C

Bovine Mastitisb d

Cefoperazone Cephalothing

Poultryc

Spectinomycin

Gentamicin e

Clindamycin

Erythromycin

Horses

Sulfonamides Trimethoprimsulfamethoxazole j

Erythromycin

Erythromycin Sulfonamides Trimethoprimsulfamethoxazole j

Dogs and Cats

Amikacin (cats only) Gentamicin (cats only)

Cephalothin (cats only) Cephalexin (cats only) Cefazolin (cats only) Sulfonamides Trimethoprim-sulfamethoxazole j

F o r U s e W i t h V E T 0 1

Clindamycin (cats only) Erythromycin

Ampicillinf Oxacillinh Penicillin

Sulfonamides

Erythromycin

y l – s e Swine e v i i c t c Apramycin c e i f s e p i t l — S r e t Spectinomycin o c e n S y i c p i C r o , r o S f p t - k s p p a i c n e u e n a i e a e T R o r r e p m r y S Cefquinomed G t e u B r a V H m o i r N P Tylosin

Cattlea Cefquinomed

Erythromycin

Chloramphenicolk

Oxacillin h Penicillin

Penicillin (turkeys only)

Tetracyclinei

Chloramphenicolk

Tetracyclinei

Tetracyclinei

Bovine Mastitisb Kanamycincephalexind

Poultryc Spectinomycin

Ceftiofur (chickens only)d Tylosin

Doxycycline (cats only) Tetracycline (cats only) i

Horses Cefquinome

Dogs and Cats Spectinomycin

Ceftiofur (dogs only)

Cefquinomed Clindamycine

V E T 0 8 , 4 t h e d .

1 5

Table 1 Antimicrobial Agents That Could Be Considered for Routine Testing Testing


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Table 1. (Continued)

Cefpodoxime Cefovecin Ceftiofur Danofloxacin Marbofloxacin Enrofloxacin Pradofloxacin Florfenicol Orbifloxacin Tildipirosin Gamithromycin

Antimicrobial Agent(s) Penicillin-novobiocin Pirlimycin Tulathromycin

Tiamulin Tilmicosin

Pharmaceutical Pharmaceutical Industry Sponsor Zoetis

Bayer HealthCare LLC

Location Parsippany, New Jersey, USA

Contact Information +1.800.733.5500

Merck Animal Health

Shawnee Mission, Kansas, USA Madison, New Jersey, USA

+1.800.521.5767

Merial

Duluth, Georgia, USA

+1.888.637.4251

Elanco Animal Health

Greenfield, Greenfiel d, Indiana, USA

+1.800.843.3386


+1.800.422.9874

Footnotes

a.

Does not include goats or sheep.

b.

Only compounds approved for use in lactating lactating dairy cattle by intramammary intramammary infusion are listed.

c.

Includes chickens and turkeys.

d.

This drug is not approved in the United States and Canada, Canada, or this drug is prohibited from certain extra-label extra-label uses in the United States, but may be approved in other countries. (Check country and local regulations; also, see NOTE 5 for website references).

e.

Clindamycin is is used to to test for susceptibility susceptibility to lincomycin. In poultry, lincomycin lincomycin is for chickens only.

f .

Ampicillin is the class representative for aminopenicillins aminopenicillins and should be tested.

g.

The results of cephalothin susceptibility tests are used to predict predict susceptibility susceptibility to cephapirin for bovine mastitis. mastitis.

h.

The results of oxacillin oxacillin susceptibility susceptibility tests are used to predict predict susceptibility to cloxacillin. Oxacillin-resistant Oxacillin-resistant staphylococci staphylococci should be reported as resistant resistant to all -lactams.

i.

The results of tetracycline tetracycline susceptibility susceptibility tests tests are used to predict susceptibility susceptibility for chlortetracycline chlortetracycline and oxytetracycline. Alternatively, chlortetracycline chlortetracycline or oxytetracycline can be used for primary testing. testing.

1 7

Table 1 Antimicrobial Agents That Could Be Considered for Routine Testing Testing

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Table 1 Antimicrobial Agents That Could Be Considered for Routine Testing Testing 1 8

Table 1. (Continued) j.

The results of trimethoprim-sulfamethoxazole trimethoprim-sulfamethoxazole can be used to to predict the susceptibility susceptibility of potentiated sulfonamides sulfonamides containing trimethoprim. trimethoprim. There are no data on the ability of trimethoprim-sulfamethoxazole trimethoprim-sulfamethoxazole results to predict susceptibility to ormetoprim-sulfadimethoxine combinations. Trimethoprim-sulfadiazine and ormetoprim-sulfadimethoxine are approved in dogs.

k.

Chloramphenicol is banned from use in food animals in in the United States States and many other countries; therefore, it must not be reported with any food-producing animal animal species.

l.

Due to extended residue residue times, times, extra-label extra-label use of aminoglycosides in cattle cattle should be avoided.

m.

Breakpoints were were established based on the extra-label extra-label use of of this drug.

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1 9

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Table 2A. Enterobacteriaceae (Continued) Test/ Report Body Antimicrobial Group Site Agent Aminoglycosides/Aminocyclitols Dogs A Amikacin

A

Organism

E. coli

Disk Content

Interpretive Categories and Zone Diameter Breakpoints, nearest whole mm


S

I

R

S

I

R

–

–

–

–

≤4

8

≥ 16

10 g

≥ 16

13–15

≤ 12

≤2

4

≥8

Comments

(5) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For dogs, the dose of amikacin modeled was 15 mg/kg, every 24 hours IM, IV, or SC. (6) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For dogs, the dose of gentamicin modeled was 10 mg/kg every 24 hours IM.

Gentamicin

Enterobacteriaceae

Horses (foals) A

Amikacin

E. coli

–

–

–

–

≤2

4

≥8

(7) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For foals < 11 days of age, the dose of amikacin modeled was 20 mg/kg, every 24 hours IV.

Horses (adults) A

Amikacin

E. coli

–

–

–

–

≤4

8

≥ 16

(8) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For adult horses, the dose of amikacin modeled was 10 mg/kg, every 24 hours, IM or IV.

Gentamicin

Enterobacteriaceae

10 g

≥ 16

13–15

≤ 12

≤2

4

≥8

(9) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For horses, the dose of gentamicin modeled was 6.6 mg/kg every 24 hours IM.

A

2 1

Table 2A Enterobacteriaceae


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Table 2A. Enterobacteriaceae 2A. Enterobacteriaceae (Continued) (Continued) Test/ Antimicrobial Report Body Agent Group Site Penicillins (Continued) Cats A

Cattle A

Skin, soft tissue, UTI

Organism

Disk Content

Interpretive Categories and Zone Diameter Breakpoints, nearest whole mm S I R

Interpretive Categories and MIC Breakpoints, µg/mL S I R

Comments

Ampicillin

E. coli

–

–

–

–

≤ 0.25

0.5

≥ 1.0

(15) Ampicillin breakpoints were determined from an examination of MIC distribution data and PK-PD analysis of amoxicillin in cats. The dosage regimen used for PK-PD analysis of amoxicillin was 12.5 mg/kg administered every 12 hours orally.

Metritis Ampicillin

E. coli

–

–

–

–

≤ 0.25

0.5

≥ 1.0

(16) Breakpoints were derived from microbiological and PK-PD data. The dose of ampicillin trihydrate used to derive this breakpoint was 11 mg/kg every every 24 hours hours IM.


Humans (17) When fecal isolates of Salmonella of Salmonella and and Shigella Shigella spp. spp. are tested, only ampicillin, a fluoroquinolone, fluoroquinolone, and trimethoprim-sulfamethoxa trimethoprim-sulfamethoxazole zole should be reported routinely. In addition, for extraintestinal extraintestinal isolates of Salmonella spp., a 3rd-generation cephalosporin should be tested and reported, and chloramphenicol may be tested and reported, if requested. Susceptibility testing is indicated for typhoidal Salmonella typhoidal Salmonella ( ( Salmonella Typhi Salmonella Typhi and Salmonella and Salmonella Paratyphi Paratyphi A–C) isolated from extraintestinal extraintestinal and intestinal sources. Routine susceptibility testing is not indicated for nontyphoidal Salmonella nontyphoidal Salmonella spp. spp. isolated from intestinal sources. In contrast, susceptibility testing is indicated for all Shigella all Shigella isolates. isolates. 10 µg ≥ 17 14–16 ≤ 13 ≤8 16 ≥ 32 (18) Results of ampicillin testing can be Enterobacteriaceae Ampicillin used to predict results for amoxicillin.

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Table 2A. Enterobacteriaceae (Continued)

Test/ Report Body Antimicrobial Group Site Agent Organism β-Lactam Combination Agents (Continued) Cats A E. coli Skin, soft Amoxicillintissue, clavulanate UTI

Disk Content



S

I

R

S

I

R

–

–

–

–

 0.25/ 0.12

0.5/0.25

 1/0.5

20/10 g

 18

14 – 17 17

 13

 8/4

16/8

 32/16

100/10 g

 21

18–20

 17

 16/4

32/4–64/4

128/4

Comments


Amoxicillin-clavulanate (23) Amoxicillin-clavulanate breakpoints were determined determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of amoxicillin in cats at a dosage of 12.5 mg/kg (amoxicillin) administered every 12 hours orally.

Humans

Amoxicillinclavulanate

Enterobacteriaceae

Enterobacteriaceae Piperacillintazobactam Cephalosporins Cephalosporins I and III (see Glossary I).

(24) Enterobacter, Citrobacter, and Serratia may develop resistance during prolonged therapy with 3rd-generation cephalosporins cephalosporins as a result of derepression of AmpC lactamase. Therefore, Therefore, isolates that are initially susceptible may become resistant within 3 to 4 days after initiation of therapy. Testing of repeat isolates may be warranted. Dogs A

Skin, soft tissue

Cephalexin

E. coli

–

–

–

–

≤2

4

≥8

(25) Cephalexin breakpoints were determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of cephalexin in dogs. The dosage regimen used for PK-PD analysis of cephalexin was 25 mg/kg administered every 12 hours orally.

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Table 2A. Enterobacteri 2A. Enterobacteriaceae aceae (Continued) (Continued) Test/ Report Antimicrobial Group Body Site Agent Organism Cephalosporins Cephalosporins I and III (see Glossary I) (Continued) Horses A Respiratory, Cefazolin E. coli genital Swine Respiratory Ceftiofur Salmonella

Disk Content


Interpretive Categories and MIC Breakpoints, Breakpoints, µg/mL

S

I

R

S

I

R

–

–

–

–

≤2

4

≥8

30 µg

≥ 21

18–20

≤ 17

≤2

4

≥8

30 µg

≥ 23

20–22

≤ 19

≤2

4

≥8

Comments

See comment (27).


cholerasuis

Humans

Cefazolin

UTIb

Cefazolin

Enterobacteriaceae Enterobacteriaceae

Enterobacteriaceae Enterobacteriaceae

30 µg

≥ 15

–

≤ 14

≤ 16

–

≥ 32

(28) Breakpoints when cefazolin is used for therapy of infections other than uncomplicated UTIs due to E. to E. coli, K. coli, K. pneumoniae, pneumoniae, and and P. P. mirabilis mirabilis.. Breakpoints are based on a dosage regimen of 2 g every 8 hours. Also refer to CLSI document M100,1 Table 2A, comment (9). (29) Cephems (parenteral): Breakpoints when cefazolin is used for therapy of uncomplicated UTIs due to E. to E. coli, K. coli, K. pneumoniae, pneumoniae, and and P. P. mirabilis. mirabilis. Breakpoints are based on a dosage regimen of 1 g every 12 hours. See additional information in CLSI document M1001 for cephems (oral). c

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Table 2A. Enterobacteriaceae (Continued) Test/ Report Antimicrobial Body Site Group Agent Fluoroquinolonesd (Continued) Dogs (Continued) A Skin, soft tissue, UTI A Skin, UTI

Organism

Orbifloxacin

Enterobacteriaceae

Pradofloxacin

Disk Content


Interpretive Categories and MIC Breakpoints, µg/mL S I R

10 µg

≥ 23

18–22

≤ 17

≤1

2–4

≥8

E. coli

5 µg

≥ 24

20–23

≤ 19

≤ 0.25

0.5–1

≥2

Comments


(32) Pradofloxacin breakpoints were determined using a dose of 3 mg/kg once daily of an oral tablet for dogs.

Cats

A

Skin, soft tissue

Enrofloxacin

Enterobacteriaceae

5 µg

≥ 23

17–22

≤ 16

≤ 0.5

1–2

≥4

A

Skin, soft tissue

Marbofloxacin

Enterobacteriaceae

5 µg

≥ 20

15–19

≤ 14

≤1

2

≥4

A

Skin, soft

Orbifloxacin

Enterobacteriaceae

10 µg

≥ 23

18–22

≤ 17

≤1

2–4

≥8

Skin, respiratory

Pradofloxacin

E. coli

5 µg

≥ 24

20–23

≤ 19

≤ 0.25

0.5–1

≥2

Skin, soft tissue, respiratory

Enrofloxacin

E. coli

–

–

–

–

≤ 0.12

0.25

≥ 0.5

(34) Enrofloxacin breakpoints were determined from an examination examination of MIC distribution data and PK-PD analysis of enrofloxacin, after administration administration of enrofloxacin at a dose of 7.5 mg/kg every 24 hours orally.

Enrofloxacin

E. coli

5 µg

≥ 23

17–22

≤ 16

≤ 0.25

0.5–1

≥2

(35) The US approval for poultry was withdrawn in September 2005.

tissue A

Horses A

Poultry A

(33) Pradofloxacin breakpoints were determined using a dose of 3 mg/kg once daily of an oral tablet or 5 mg/kg once daily of an oral suspension for cats.

2 9


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Table 2A. Enterobacteriaceae (Continued)

Test/ Report Group Body Site Tetracyclines Horses A Respiratory, skin, soft tissue

A

Respiratory, skin, soft tissue

Antimicrobial Agent

Doxycycline

Minocycline

Organism

E. coli

E. coli

Disk Content

–

–



S

I

R

S

I

R

–

–

–

 0.12

0.25

 0.5

–

–

–

≤ 0.12

0.25

≥ 0.5

Comments


(40) Doxycycline breakpoints were derived from microbiological and PK-PD analysis using a clinical dose of 20 mg/kg, orally, twice daily to horses, and PD data. (41) Do not test tetracycline as a surrogate for doxycycline and minocycline in horses. (42) Minocycline breakpoints were derived from microbiological and PK-PD analysis using a clinical dose of 5 mg/kg, orally, twice daily to horses, and PD data. See comment (41).

Humans (43) Tetracycline tested as the class representative for susceptibility to chlortetracycline, doxycycline, minocycline, and oxytetracycline. c (44) Organisms that are susceptible to tetracycline are also considered susceptible to do xycycline and minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible susceptible to doxycycline, minocycline, minocycline, or both. Enterobacteriaceae Tetracycline 30 µg ≥ 15 12–14 ≤ 11 ≤4 8 ≥ 16 Enterobacteriaceae Doxycycline 30 µg ≥ 14 11–13 ≤ 10 ≤4 8 ≥ 16 Enterobacteriaceae Minocycline 30 µg ≥ 16 13–15 ≤ 12 ≤4 8 ≥ 16 Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton broth; I, intermediate; IM, intramuscularly; IV, intravenously; MHA, MuellerHinton agar; MIC, minimal inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; PK-PD, pharmacokinetic-pharmacodynamic; pharmacokinetic-pharmacodynamic; QC, quality control; R, resistant; S, susceptible; SC, subcutaneously; UTI, urinary tract infection. Footnotes

3 1

a.


b.

Body site “UTI” “UTI” added added to entries listed listed in in CLSI document M1001 as test/report group U.

c.

This comment comment on a human breakpoint breakpoint is not not found in CLSI document M100 1; it has been added to VET08 for veterinary application.

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Table 2A Enterobacteriaceae 3 2

Table 2A. Enterobacteriaceae (Continued) d.

Testing and reporting reporting ciprofloxacin ciprofloxacin is not recommended for any any veterinary species species because PK-PD analysis does does not support its use. Additionally, isolates isolates that are intermediate or resistant to any fluoroquinolone fluoroquinolone may be at increased risk of developing resistance to all fluoroquinolones.

References for Table 2A 1

CLSI. Performance CLSI. Performance Standards for Antimicrobial Antimicrobial Susceptibility Susceptibility Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

2

CLSI. Performance CLSI. Performance Standards for Antimicrobial Antimicrobial Disk and Dilution Susceptibility Susceptibility Tests for Bacteria Isolated From Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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3 3


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Table 2B. Pseudomonas 2B. Pseudomonas aeruginosa aeruginosa (Continued) (Continued) Test/ Report Body Antimicrobial Group Site Agent Aminoglycosides/Aminocyclitols Dogs A Amikacin

A

Gentamicin

Disk Content


–

–

–

10 g

 16

13–15

–

Interpretive Categories and MIC Breakpoints, Breakpoints, µg/mL S I R

≤4

8

≥ 16

 12

2

4

8

Comments

(5) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For dogs, the dose of amikacin modeled was 15 mg/kg every 24 hours, IM, IV, or SC. (6) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For dogs, the dose of gentamicin modeled was 10 mg/kg every 24 hours, IM.

Horses (foals) A

Amikacin

–

–

–

–

2

4

8

(7) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For foals < 11 days of age, the d ose of amikacin modeled was 20 mg/kg, every 24 hours IV.

Horses (adults) A

Amikacin

–

–

–

–

4

8

 16

(8) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For adult horses, the dose of amikacin modeled was 10 mg/kg, every 24 hours IM or IV.

Gentamicin

10 g

 16

13–15

 12

2

4

8

(9) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For horses, the dose of gentamicin modeled was 6.6 mg/kg every 24 hours IM.

Amikacin Gentamicin

30 g 10 g

 17

15–16 13–14

 14

 16 4

32 8

 64

 12


Horses

Humans  15

 16

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3 5

Table 2B Pseudomonas aeruginosa Pseudomonas


©


aeruginosa (Continued) Table 2B. Pseudomonas aeruginosa References for Table 2B 1


2

CLSI. Performance CLSI. Performance Standards for Antimicrobial Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated Isolated From Animals. Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.


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3 7

Table 2B Pseudomonas aeruginosa Pseudomonas


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Table 2C. Staphylococcus 2C. Staphylococcus spp. spp. (Continued)

Test/ Report Antimicrobial Group Body Site Agent Aminoglycosides/Aminocyclitols Dogs A Amikacin

Organism

Disk Content

Staphylococcus spp.

Horses (foals) A

Amikacin

Horses (adults) A

Amikacin



S

I

R

S

I

R

–

–

–

–

4

8

 16

(5) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For dogs, the dose of amikacin modeled was 15 mg/kg, every 24 hours IM, IV, or SC.

S. aureus

–

–

–

–

2

4

8

(6) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For foals < 11 days of age, the dose of amikacin modeled was 20 mg/kg, every 24 hou rs IV.

S. aureus

–

–

–

–

4

8

 16


Humans (8) For staphylococci that test susceptible, gentamicin is used only in combination with other active agents that test susceptible. Gentamicin Staphylococcus spp. Staphylococcus spp. 13–14 8 10 g  15  12 4 Ansamycins Humans Rifampin Staphylococcus spp. Staphylococcus spp. 17–19 2 5 g  20  16 1

Comments


 16

4

(9) Rx: Rifampin should not be used alone for antimicrobial therapy.

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3 9

Table 2C Staphylococcus spp.


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Table 2C. Staphylococcus 2C. Staphylococcus spp. spp. (Continued) Interpretive Categories and Zone Diameter Breakpoints, nearest whole mm


Test/ Report Antimicrobial Disk Group Body Site Agent Organism Content S I R S I R Comments Penicillinase-labile Penicillinase-labile penicillins (Continued) Humans (14) Penicillin-susceptible staphylococci staphylococci are susceptible to other -lactam agents with established clinical efficacy for staphylococcal infections (including both penicillinase-labile penicillinase-labile and penicillinase-stable penicillinase-stable agents; see Glossary I). Penicillin-resistant staphylococci are resistant to penicillinase-labile penicillinase-labile penicillins.

Penicillin

Staphylococcus spp.

10 units

 29

–

 28

 0.12

–

 0.25


(15) Penicillin should be used to test the susceptibility of all staphylococci to all penicillinase-labile penicillinase-labile penicillins. Penicillinresistant strains of staphylococci produce β-lactamase. Perform a test(s) to detect βlactamase production on staphylococci for which the penicillin MICs are ≤ 0.12 µg/mL or zone diameters ≥ 29 mm before reporting the isolate as penicillin susceptible. Rare isolates of staphylococci that contain genes for βlactamase production may appear negative by β-lactamase tests. Consequently, for serious infections requiring penicillin therapy, laboratories should perform MIC tests and βlactamase testing on all subsequent isolates from the same patient. PCR testing of the isolate for the blaZ blaZ βlactamase gene may be considered. See CLSI document M1001 Tables 3D and 3E.

staphylococci, (16) For oxacillin-resistant staphylococci, report penicillin as resistant or do not report.

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Test/ Report Body Antimicrobial Group Site Agent Organism Penicillinase-stable Penicillinase-stable penicillins (Continued) Humans Oxacillin S. aureus and aureus and S. lugdunensis

Disk Content

–

30 g cefoxitin (surrogate test for oxacillin)



S

I

R

S

I

–

–

–

2 (oxacillin)

–

 22

–

 21

4 (cefoxitin)

–

R

Comments

For use with S. with S. aureus and aureus and S. S. lugdunensis. 4 (oxacillin) (20) Oxacillin is used to test for susceptibility to methicillin, nafcillin, and cloxacillin. S. aureus breakpoints aureus breakpoints should be used for strains of S. aureus and not for other coagulase positive staphylococci isolated from veterinary veterinary sources such as S. pseudintermedius.c (21) Oxacillin disk testing is not reliable. See cefoxitin and comment (19) for reporting oxacillin when testing cefoxitin as a surrogate agent. (22) Cefoxitin is tested as a surrogate for 8 (cefoxitin) oxacillin. Isolates that test resistant by cefoxitin MIC, cefoxitin disk, or oxacillin MIC should be reported as oxacillin resistant. If testing only cefoxitin, report oxacillin susceptible or resistant based on the cefoxitin result. (23) Cefoxitin MIC and disk diffusion tests performed on media other than CAMHB or unsupplemented MHA do not reliably detect mecA-mediated mecA -mediated resistance in isolates of S. aureus that aureus that do not grow well on these media (eg, small colony variants). Testing for PBP2a using induced growth (ie, growth taken from the zone margin surrounding a cefoxitin disk on either BMHA or a blood agar plate after 24 hours incubation in 5% CO2) or mecA mecA should should be done. Isolates that test either mecA mecA negative negative or PBP2a negative or cefoxitin susceptible should be reported as oxacillin susceptible.

4 3


See comments (14), (17), (18), and (19).


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Test/ Report Body Antimicrobial Group Site Agent Organism β-Lactam Combination Agents Dogs A Skin, AmoxicillinStaphylococcus spp. Staphylococcus spp. soft clavulanate tissue

Disk Content

–



S

I

R

S

I

R

–

–

–

 0.25/

0.5/0.25

 1/0.5

0.12

A

UTI


Staphylococcus spp. Staphylococcus spp.

–

–

–

–

 8/4

–

–

A


Piperacillintazobactam

Staphylococcus Staphylococcus spp.

–

–

–

–

≤ 8/4

16/4

≥ 32/4

Comments


Amoxicillin-clavulanate (28) Amoxicillin-clavulanate breakpoints were determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of amoxicillin in dogs. The dosage regimen used for PK-PD analysis of amoxicillin was 11 mg/kg administered every 12 hours orally. (29) This breakpoint was derived from published literature in which orally administered ampicillin 25.6 mg/kg and amoxicillin 11 mg/kg were administered to healthy dogs at 8-hour intervals for 5 consecutive doses and produced urine concentrations of > 300 µg/mL. (30) Piperacillin-tazobactam Piperacillin-tazobactam breakpoints were derived from published PK studies in dogs, an examination examination of MIC distribution data, and PK-PD analysis of piperacillin in dogs at a dosage of 350 mg/kg every 6 hours IV or 3.2 mg/kg/hour constant rate IV infusion.

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Table 2C. Staphylococcus 2C. Staphylococcus spp. spp. (Continued) Test/ Report Antimicrobial Group Body Site Agent Cephalosporins Cephalosporins (Continued) Dogs (Continued) A Skin, soft tissue

Cephalothin

Organism

Disk Content

Interpretive Categories and Interpretive Categories and Zone Diameter Breakpoints, MIC Breakpoints, nearest whole mm µg/mL S

I

R

S

I

R

Comments

S. aureus and aureus and S. pseudintermedius

–

–

–

–

2

4

8

(33) Cephalothin breakpoints were determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of cephalexin. The dosage regimen used for PK-PD analysis of cephalexin was 25 mg/kg administered every 12 hours orally. (34) Cefazolin breakpoints were determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of cefazolin. The dosage regimen used for PK-PD analysis of cefazolin was 25 mg/kg administered every 6 hours IV in dogs.

A

Skin, soft Cefazolin tissue, UTI, respiratory

S. aureus and S. pseudintermedius

–

–

–

–

 2

4

 8

A

Wounds, abscesses

Cefpodoxime

S. aureus and S. pseudintermedius

10 g

 21

18–20

 17

 2

4

 8

Mastitis

Ceftiofur

S. aureus

30 g

 21

18–20

 17

2

4

8

Difloxacin

Staphylococcus spp. Staphylococcus spp.

10 g

 21

18–20

 17

 0.5

1–2

4

5 g

 23

17–22

 16

 0.5

1–2

4

Staphylococcus spp. Staphylococcus spp. S. pseudintermedius

5 g

 20

15–19

 14

1

2

4

10 g

 23

18–22

 17

1

2–4

8

5 g

 24

20–23

 19

 0.25

0.5–1

2

Cattle A


Fluoroquinolonesd Dogs A

A

A A A

Skin, soft tissue, UTI Skin, soft tissue, UTI, respiratory Skin, soft tissue, UTI Skin, soft tissue, UTI Skin, UTI

Enrofloxacin

Marbofloxacin Orbifloxacin Pradofloxacin

(35) Pradofloxacin breakpoints were determined using a dose of 3 mg/kg once daily of an oral tablet for dogs.

4 7


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Table 2C. Staphylococcus 2C. Staphylococcus spp. spp. (Continued) Interpretive Categories and Zone Diameter Breakpoints, Interpretive Categories and nearest whole mm MIC Breakpoints, µg/mL

Test/ Report Antimicrobial Disk Group Body Site Agent Organism Content S I R S I R Glycopeptides Humans intermediate during the course of pr olonged therapy. (37) For S. aureus, vancomycin-susceptible isolates may become vancomycin intermediate Vancomycin – – – – ≤2 4–8 S. aureus  16

Comments


(39) MIC tests should be performed to determine the susceptibility of all isolates of staphylococci to vancomycin. The disk test does not differentiate vancomycinsusceptible isolates of S. aureus from vancomycin-intermediate isolates, nor does the test differentiate among vancomycin-susceptible, -intermediate, and -resistant isolates of CoNS, all of which will give similar size zones of inhibition. (40) Send any S. aureus for which the vancomycin is  8 g/mL to a reference laboratory. See Appendix A.c

Vancomycin

CoNS

–

–

–

–

4

8–16

 32

(41) See Table 7E for S. aureus, and aureus, and refer to VET01, 2 Subchapter 7.2.3 and Appendix D.c See comment (39). (42) Send any CoNS for which the vancomycin MIC is  32 g/mL to a reference laboratory. See Appendix A.c (43) Refer to VET01, 2 Subchapter 7.2.3. c

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Test/ Report Group Body Site Tetracyclines Dogs A Skin, soft tissue

Antimicrobial Agent

Organism


S

I

R

S

I

R

 0.5

Doxycycline

S. pseudintermedius

30 g

 25

21–24

 20

 0.12

0.25

–

–

–

–

 0.5

1

30 g

 23

18–22

 17

 0.25

0.5

–

–

–

–

 0.12

0.25

A

Skin, soft tissue

Minocycline

S. pseudintermedius pseudintermedius

A

Skin, soft tissue

Tetracycline

Staphylococcus spp.

Respiratory, skin, soft tissue

Doxycycline

S. aureus

Horses A

Disk Content


Comments


(49) Doxycycline breakpoints were derived from microbiological and PK data using a clinical dose of 5 mg/kg, orally, twice daily, and PD data. (50) Minocycline breakpoints were derived 2 from microbiological and PK-PD analysis using a clinical dose of 5 mg/kg, orally, twice daily to fasted dogs, and PD data. These breakpoints only apply to dogs administered administered minocycline under fasting conditions. Administering minocycline with food will significantly reduce drug availability and may result in clinical failure.  1.0 (51) Tetracycline tested as the class representative for susceptibility to chlortetracycline, o xytetracycline, xytetracycline, doxycycline, and minocycline.c Organisms that are susceptible to tetracycline are also considered susceptible to other members of the class. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline doxycycline or minocycline or both.  0.5

(52) Doxycycline breakpoints were derived from microbiological and PK-PD analysis using a clinical dose of 20 mg/kg, orally, twice daily to horses, and PD data. (53) Do not test tetracycline as a surrogate for doxycycline and minocycline in horses.

5 1


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Table 2C. Staphylococcus 2C. Staphylococcus spp. spp. (Continued) 4

Fessler AT, Billerbeck C, Kadlec K, Schwarz S. Identification and characterization of methicillin-resistant coagulase-negative coagulase-negative staphylococci from bovine mastitis. J Antimicrob Antimicrob Chemother . 2010;65(8):1576-1582.

5

Monecke S, Müller E, Schwarz S, Hotzel H, Ehricht R. Rapid microarray-based identification of different mecA alleles mecA alleles in staphylococci. Antimicrob Agents Chemother . 2012;56(11):5547-5554.


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Table 2D. Streptococcus 2D. Streptococcus spp. (Continued)

Test/ Report Antimicrobial Group Body Site Agent Aminoglycosides/Aminocyclitols Dogs A Amikacin

Organism

Disk Content



S

I

R

S

I

R

Comments

Streptococcus spp.

–

–

–

–

4

8

 16

(5) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For dogs, the dose of amikacin modeled was 15 mg/kg, every 24 hours, IM, IV, or SC.

Horses (foals) A

Amikacin

Streptococcus equi subsp. zooepidemi subsp. zooepidemicus cus and subsp. equi

–

–

–

–

2

4

8

(6) Breakpoints were derived from microbiological, PK (using accepted clinical doses), and PD data. For foals < 11 days of age, the dose of amikacin modeled was 20 mg/kg, every 24 hours IV.

Horses (adults) A

Amikacin

S. equi subsp. equi and subsp. zooepidemi subsp. zooepidemicus cus

–

–

–

–

4

8

 16


Streptococcus spp.

–

–

–

–

 0.25/

0.5/0.25

 1/0.5

Amoxicillin-clavulanate (8) Amoxicillin-clavulanate breakpoints were determined determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of amoxicillin in cats at a dosage of 12.5 mg/kg (amoxicillin) administered every 12 hours orally.

β-Lactam Combination Agents Cats A Skin, soft Amoxicillintissue, UTI clavulanate

0.12

5 5

Table 2D Streptococcus spp.


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Table 2D. Streptococcus 2D. Streptococcus spp. (Continued) Test/ Report Antimicrobial Group Body Site Agent Organism Penicillins (Continued) Horses (Continued) A Respiratory, Penicillin G Streptococcus spp. soft tissue

Swine A

A

Respiratory

Disk Content

Interpretive Categories and Zone Diameter Breakpoints, Interpretive Categories and nearest whole mm MIC Breakpoints, µg/mL S

I

R

S

I

R

–

–

–

–

 0.5

1

2

(14) Breakpoints were derived from microbiological, PK data (using accepted clinical but extra-label doses), and PD data. The dose o f procaine penicillin G modeled was 22 000 U/kg every every 24 hours hours IM. (15) Breakpoints were derived from microbiological data using ampicillin, PK data from a dose of 15 mg/kg IM of amoxicillin once daily, and PD data. (16) Breakpoints were derived from microbiological, PK data (using accepted clinical but extra-label doses), and PD data. The dose o f procaine penicillin G modeled was 33 000 U/kg every 24 hours IM by needle in the neck.

Ampicillin

Streptococcus suis

–

–

–

–

 0.5

1

2

Penicillin G

S. suis

–

–

–

–

 0.25

0.5

1

Comments


Humans (17) Susceptibility testing of penicillins and other -lactams approved for treatment of β-hemolytic streptococcal streptococcal infections does not need to be performed routinely, because nonsusceptible isolates (ie, penicillin MICs > 0.12 and ampicillin MICs > 0.25 µg/mL) are extremely rare in any β-hemolytic streptococcus streptococcus and have not been reported for S . pyogenes. pyogenes. If testing is performed, any β-hemolytic streptococcal streptococcal isolate found to be nonsusceptible should be re-identified, retested, and, if confirmed, submitted to a public health laboratory. (For veterinary application, see Appendix A for additional instructions. b) (18) An organism that is susceptible to penicillin can be considered susceptible to antimicrobial antimicrobial agents listed here when used for approved indications and does not need to be tested against those agents. For groups A, B, C, and G β-hemolytic streptococci, streptococci, penicillin is a surrogate for ampicillin, amoxicillin, amoxicillin, amoxicillin-clavulanate, amoxicillin-clavulanate, ampicillin-sulbactam, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, cephradine, cephalothin, cefotaxime, ceftriaxone, ceftizoxime, imipenem, ertapenem, and meropenem. For group A β-hemolytic streptococci, penicillin is also a surrogate for cefaclor, cefdinir, cefprozil, ceftibuten, cefuroxime, and cefpodoxime. Ampicillin Streptococcus spp. – – – – -hemolytic group 10 g  24  0.25

Viridans groupc

–

–

–

 0.25

0.5–4

8

5 7


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Table 2D Streptococcus spp. 5 8

Table 2D. Streptococcus 2D. Streptococcus spp. (Continued)

Test/ Report Antimicrobial Group Body Site Agent Organism Penicillins (Continued) Humans (Continued) Penicillin G Streptococcus spp. -hemolytic group (not S. pneumoniae pneumoniae) Streptococcus spp. viridans groupc (not S. pneumoniae pneumoniae)

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Oxacillin (surrogate for Penicillin G)

S. pneumoniae

Disk Content

Interpretive Categories and Zone Diameter Interpretive Categories and Breakpoints, MIC Breakpoints, nearest whole mm µg/mL S

I

R

S

I

R

10 units

 24

–

–

 0.12

–

–

–

–

–

–

 0.12

0.25–2

4

1 g

 20

–

–

–

–

–

Comments

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(19) Isolates of pneumococci with oxacillin zone sizes of  20 mm are susceptible (MIC  0.06 g/mL) to penicillin. Penicillin and cefotaxime, ceftriaxone, or meropenem MICs should be determined for those isolates with oxacillin zone diameters of  19 mm, because zones of  19 mm occur with penicillin-resistant, penicillin-resistant, -intermediate, or certain -susceptible strains. For isolates with oxacillin zones  19 mm, do not report penicillin as resistant without performing a penicillin MIC test.



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Table 2D. Streptococcus 2D. Streptococcus spp. (Continued) Test/ Report Group Body Site Carbapenems Humans

Antimicrobial Agent

Imipenem

Other Class Combinations Cattle A Mastitis Penicillinnovobiocin Cephalosporins Dogs A Skin, soft tissue A Skin, soft tissue

A

Skin, soft tissue

Cefovecin Cephalexin

Cephalothin

Organism

Disk Content



S

I

R

S

I

R

–

–

–

–

 0.12

0.25– 0.5

1

Streptococcus agalactiae Streptococcus dysgalactiae Streptococcus uberis

10 units/ 30 g

 18

15–17

 14

 1/2

2/4

 4/8

Streptococcus Streptococcus spp. β-hemolytic group Streptococcus Streptococcus spp. spp. β-hemolytic group

30 µg

≥ 24

21–23

≤ 20

 0.12

0.25

 0.5

–

–

–

–

2

4

8

Streptococcus spp. Streptococcus spp. β-hemolytic group

–

–

–

–

2

4

8

S. pneumoniae

Comments

(20) See CLSI document M1002 for comments on carbapenems and human medical breakpoints for imipenem.b

(21) Cephalexin breakpoints were determined from an examination examination of MIC distribution data, efficacy data, and PK-PD analysis of cephalexin. The dosage regimen used for PK-PD analysis of cephalexin was 25 mg/kg administered every 12 hours orally. (22) Cephalothin breakpoints were determined from an examination of MIC distribution data, efficacy data, and PK-PD analysis of cephalexin. The dosage regimen used for PK-PD analysis of cephalexin was 25 mg/kg administered every 12 hours orally.

5 9



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Table 2D. Streptococcus 2D. Streptococcus spp. (Continued) Test/ Report Antimicrobial Group Body Site Agent Cephalosporins Cephalosporins (Continued) Cattle A Mastitis Ceftiofur

Fluoroquinolonesd Dogs A Skin, soft tissue, respiratory, UTI

Organism

Disk Content



S

I

R

S

I

R

S. agalactiae S. dysgalactiae S. uberis

30 g

 21

18–20

 17

2

4

8

Enrofloxacin

Streptococcus spp. spp.

5 µg

≥ 23

17–22

≤ 16

≤ 0.5

1–2

≥4

A


Difloxacin

Streptococcus spp.

10 µg

≥ 21

18–20

≤ 17

≤ 0.5

1–2

≥4

A


Marbofloxacin


5 µg

≥ 20

15–19

≤ 14

≤1

2

≥4

A


Orbifloxacin

Streptococcus spp.

10 µg

≥ 23

18–22

≤ 17

≤1

2–4

≥8

Skin, soft tissue

Enrofloxacin

Streptococcus spp.

5 g

 23

17–22

 16

 0.5

1–2

4

A

Skin, soft tissue

Marbofloxacin

Streptococcus spp.

5 g

 20

15–19

 14

1

2

4

A

Skin, soft tissue

Orbifloxacin

Streptococcus spp.

10 g

 23

18–22

 17

1

2–4

8

A

Skin, respiratory

Pradofloxacin

S. canis (group G, -hemolytic)

5 g

 24

–

–

 0.25

–

–

Cats A

Comments


See comment (25). (26) Pradofloxacin breakpoints were determined using a dose of 3 mg/kg once daily of an oral tablet or 5 mg/kg once daily of an oral suspension.

6 1


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Table 2D. Streptococcus 2D. Streptococcus spp. (Continued) Test/ Report Antimicrobial Group Body Site Agent Organism Folate Pathway Antagonists Humans TrimethoprimS. pneumoniae sulfamethoxazole Glycopeptides Humans Vancomycin Streptococcus spp.

Disk Content



S

I

R

S

I

R

1.25/ 23.75 g

 19

16–18

 15

 0.5/9.5

1/19– 2/38

 4/76

30 g

 17

–

–

1

–

–

Comments


(31) For some organism/antimicrobial organism/antimicrobial agent combinations, the absence of resistant strains precludes defining any results categories other than “susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility test results should be confirmed. (For veterinary application, see Appendix A for additional instructions.)b

Macrolides Humans (32) Susceptibility and resistance to azithromycin, clarithromycin, and dirithromycin can be predicted by testing erythromycin. (33) Not routinely reported for organisms isolated from the urinary tract. Erythromycin Streptococcus spp. 15 g β-hemolytic group Viridans groupc S. pneumoniae Azithromycin Streptococcus Streptococcus spp. spp. 15 g β-hemolytic group Viridans groupc S. pneumoniae pneumoniae Clarithromycin Streptococcus Streptococcus spp. spp. 15 g β-hemolytic group Viridans groupc S. pneumoniae pneumoniae

 21

16–20

 15

 0.25

0.5

1

 18

14–17

 13

 0.5

1

2

 21

17–20

 16

 0.25

0.5

1

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Table 2D. Streptococcus 2D. Streptococcus spp. (Continued) Test/ Report Antimicrobial Group Body Site Agent Organism Tetracyclines Tetracyclines (Continued) Swine A Respiratory Tetracycline S. suis

Disk Content

–

Interpretive Categories and Interpretive Categories and Zone Diameter Breakpoints, MIC Breakpoints, nearest whole mm µg/mL S

I

R

S

I

R

–

–

–

 0.5

1

2

Comments

(40) Breakpoints were derived from PK data of oxytetracycline at 20 mg/kg IM, once, and PD data.


(41) These breakpoints are applicable only for the injectable formulations. Tetracycline is the class representative. Humans

Tetracycline

Streptococcus spp., other than S. neumoniae S. pneumoniae

30 g

 23

19–22

 18

2

4

8

 28

25–27

 24

1

2

4

(42) Tetracycline tested as the class representative for susceptibility to chlortetracycline, doxycycline, minocycline, and oxytetracycline.b Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline or minocycline or both.

Doxycycline 25–27 0.5 S. pneumoniae 30 g  28  24  0.25 1 Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton broth; I, intermediate; IM, intramuscularly; IV, intravenously; LHB, lysed horse blood; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; PK-PD, pharmacokinetic-pharmacodynami pharmacokinetic-pharmacodynamic; c; QC, quality control; R, resistant; S, susceptible; SC, subcutaneously; UTI, urinary tract infection. Footnotes a.

ATCC® is a registered trademark trademark of the American Type Culture Collection.

b.

This comment comment on a human human breakpoint breakpoint is not not found in CLSI document M100 M100 2; it has been added to VET08 for veterinary application.

c.

The viridans viridans group of of streptococci includes the following following five five groups, with several species within within each group: group: mutans group, mutans group, salivarius group, salivarius group, bovis group, bovis group, anginosus group (previously “ S. milleri ” group), and mitis group. mitis group. The anginosus group anginosus group includes small colony–forming β-hemolytic β-hemolytic strains with groups A, C, F, and G antigens. For detailed information on the species within the groups, please refer to recent literature.

6 5


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Table 2D Streptococcus spp. 6 6

Table 2D. Streptococcus 2D. Streptococcus spp. (Continued) d.

Testing and reporting reporting ciprofloxacin ciprofloxacin is not recommended recommended for any veterinary veterinary species species because PK-PD analysis analysis does not not support its use. Additionally, isolates that are intermediate or resistant to any fluoroquinolone fluoroquinolone may be at increased risk of developing resistance to all fluoroquinolones.

References for Table 2D 1


2


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6 7


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Table 2E. Enterococcus spp. (Continued) Test/ Report Body Group Site Ansamycins Humans

Antimicrobial Agent

Rifampin

Disk Content

5 g



S

I

R

S

I

R

Comments

 20

17–19

 16

1

2

4

(6) Rx: Rifampin should not be used alone for antimicrobial therapy.

(7) The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin amoxicillin . Ampicillin results may be used to p redict susceptibility to amoxicillinamoxicillinclavulanate, ampicillin-sulbactam, and piperacillintazobactam among non–β-lactamase-producing enterococci. Ampicillin susceptibility can be used to predict imipenem susceptibility, providing the species is confirmed to be E. be E. faecalis.


Penicillins Humans

Ampicillin

10 g

 17

–

 16

8

–

 16

Penicillin

10 units

 15

–

 14

 8

–

 16

(8) Enterococci susceptible to penicillin are predictably susceptible to ampicillin, amoxicillin, ampicillin-sulbactam, ampicillin-sulbactam, amoxicillin-clavulanate, amoxicillin-clavulanate, and piperacillin-tazobactam piperacillin-tazobactam for non–β-lactamase-producing enterococci. However, enterococci susceptible to ampicillin cannot be assumed to be susceptible to penicillin. penicillin. If penicillin penicillin results are needed, needed, testing of penicillin is required. (9) Rx: Combination therapy with ampicillin, penicillin, or vancomycin (for susceptible strains only), plus an aminoglycoside, is usually indicated for serious enterococcal infections, such as endocarditis, unless highlevel resistance to both gentamicin and streptomycin is documented; such combinations are predicted to result in synergistic killing of the Enterococcus. the Enterococcus. For strains with low-level penicillin or ampicillin resistance when combination therapy with a -lactam is being considered, also see additional testing and reporting information in Table 7G. 3

6 9

Table 2E Enterococcus spp.

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Table 2E. Enterococcus spp. (Continued)

Test/ Report Group Phenicols Humans

Antimicrobial Agent

Disk Content

Chloramphenicol

30 µg

Body Site



S

I

R

S

I

R

 18

13–17

 12

8

16

 32

Comments


(13) MIC distribution data from canine isolates support these breakpoints for use in canine skin and soft tissue infection; however, efficacy data and PK-PD targets were unavailable.b (14) Not routinely reported on isolates from the urinary tract (in humans).

Tetracyclines (15) Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline, minocycline, or both. Humans 30 µg 13–15 8  16  12 4  16 Doxycycline 30 µg 15–18 8  19  14 4  16 Minocycline 30 µg 15–18 8 UTIc  19  14 4  16 Tetracycline

Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton Mueller-Hinton broth; I, intermediate; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic; QC, quality control; R, resistant; S, susceptible. Footnotes a.


b.

This comment comment on a human breakpoint is not found in CLSI document document M1002; it has been added to VET08 for veterinary application.

c.

Body site “UTI” added to entries entries listed in CLSI CLSI document document M100 2 as test/report group U.

References for Table 2E 1


2


7 1

Table 2E Enterococcus spp.

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Table 2E Enterococcus spp. 7 2

Table 2E. Enterococcus spp. (Continued) 3

Murray BE, Arias CA, Nannini EC. Glycopeptides (vancomycin and teicoplanin), streptogramins (quinupristin-dalfopristin), lipopeptides (daptomycin), and lipoglycopeptides (telavancin). In: Bennett JE, Dolin R, Blaser MJ. Mandell, MJ. Mandell, Douglas, and Bennett’s Bennett’s Principles and Practice Practice of Infectious Infectious Diseases. 8th Diseases. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:377-400.

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Table 2F. Bordetella 2F. Bordetella bronchiseptica bronchiseptica (Continued) (Continued) Test/ Report Group Phenicols Swine

Body Site

Antimicrobial Agent

Disk Content

Interpretive Categories and Zone Diameter Breakpoints, nearest whole mm S

I

R

Interpretive Categories and MIC Breakpoints, µg/mL S

I

R

Comments

A Respiratory Florfenicol 30 µg ≥ 22 19–21 ≤ 18 ≤2 4 ≥8 (5) For premix product only. Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton Mueller-Hinton broth; I, intermediate; IM, intramuscularly; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; QC, quality control; R, resistant; S, susceptible.


Footnote a.


Reference for Table 2F 1

Schwarz S, Böttner A, Goossens L, et al. A p roposal of clinical breakpoints for amoxicillin applicable to porcine respiratory tract pathogens. 3):178-188.

Vet Microbiol .

2008;126(1-

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7 5

Table 2F Bordetella bronchiseptica


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Table 2G. Mannheimia 2G. Mannheimia haemolytica haemolytica (Continued) (Continued)

Test/ Report Group Body Site Cephalosporins Cattle A Respiratory

Ceftiofur

Fluoroquinolonesb Cattle A Respiratory

Danofloxacin

Antimicrobial Agent

Disk Content

Interpretive Categories and Zone Diameter Interpretive Categories and Breakpoints, MIC Breakpoints, nearest whole mm µg/mL S

I

R

S

I

R

30 g

 21

18 – 20 20

 17

2

4

8

5 µg

 22

18–21

≤ 17

 0.25

0.5

≥1

Comments


(4) The dose of 1.25 mg/kg is not assured to meet currently accepted PK-PD targets, and the breakpoints and interpretive categories are limited to the two approved doses (6 mg/kg twice, or 8 mg/kg once). (5) This breakpoint applies to approved labeled dosage of 6 mg/kg and 8 mg/kg.

A Respiratory Macrolides Cattle A Respiratory A A A

Enrofloxacin

5 µg

≥ 21

17–20

≤ 16

≤ 0.25

0.5–1

≥2

Gamithromycin Gamithromycin

15 µg

≥ 15

12–14

≤ 11

≤4

8

≥ 16

Respiratory

Tildipirosin

60 µg

≥ 20

17–19

≤ 16

≤4

8

≥ 16

Respiratory

Tilmicosin

15 µg

≥ 14

11–13

≤ 10

≤8

16

≥ 32

Respiratory

Tulathromycin

30 µg

≥ 18

15–17

≤ 14

≤ 16

32

≥ 64

Florfenicol

30 µg

≥ 19

15–18

≤ 14

≤2

4

≥8

Tetracycline

–

–

–

–

2

4

8

(6) For injection product only.

Phenicols Cattle

A Respiratory Tetracyclines Cattle A Respiratory

(7) Breakpoints were derived from PK data o f oxytetracycline at 20 mg/kg IM, once, and PD data.

(8) These breakpoints are applicable only for the injectable formulations. Tetracycline is the class representative. Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton Mueller-Hinton broth; I, intermediate; IM, intramuscularly; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PD, p harmacodynamic; PK, pharmacokinetic; PK-PD, pharmacokinetic-pharmacodynamic; QC, quality control; R, resistant; S, susceptible. 7 7

Table 2G Mannheimia haemolytica

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Table 2G Mannheimia haemolytica 7 8

Table 2G. Mannheimia 2G. Mannheimia haemolytica haemolytica (Continued) (Continued) Footnotes a.


b.

Testing and reporting reporting ciprofloxacin ciprofloxacin is not recommended recommended for any veterinary veterinary species as PK-PD analysis analysis does not support support its use. Additionally, isolates isolates that are intermediate or resistant to any fluoroquinolone fluoroquinolone may be at increased risk of developing resistance to all fluoroquinolones.

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7 9


V E T 0 8 , 4 t h e d .


©


8 1

Table 2H. Pasteurella multocida (Continued) Test/ Report Group Body Site Penicillins Cats A Skin, soft tissue, UTI

Swine A

Respiratory

A

Antimicrobial Agent

Disk Content



S

I

R

S

I

R

Comments

Ampicillin

–

–

–

–

 0.25

0.5

1

(3) Ampicillin breakpoints were determined from an examination of MIC distribution data and PK-PD analysis of amoxicillin in cats. The dosage regimen used for PK-PD analysis of amoxicillin was 12.5 mg/kg administered every 12 hours orally.

Ampicillin

–

–

–

–

 0.5

1

2

(4) Ampicillin is the class representative for the aminopenicillins aminopenicillins and should be tested.

Penicillin G

–

–

–

–

 0.25

0.5

1


(5) Breakpoints were derived from microbiological data using ampicillin, PK data from a dose of 15 mg/kg IM of amoxicillin once daily, and PD data. 1 (6) Breakpoints were derived from microbiological, PK data (using accepted clinical but extra-label doses), and PD data. The dose of procaine penicillin G modeled was 33 000 U/kg every 24 hours hours IM by needle in the neck.

Cattle

A

Respiratory

Ampicillin

–

–

–

–

≤ 0.03

0.06– 0.12

≥ 0.25

A

Respiratory

Penicillin G

–

–

–

–

 0.25

0.5

1

–

–

–

–

2

4

8

10 g

 21

18–20

 17

2

4

8

30 µg

≥ 24

21–23

≤ 20

 0.12

0.25

 0.5

Cephalosporins Dogs A Skin, soft tissue, Cefazolin respiratory, urinary/genital A Wounds, abscesses Cefpodoxime Cats A Skin, soft tissue Cefovecin

(7) Breakpoints were derived from microbiological and PK-PD data. The dose of ampicillin trihydrate used to derive this breakpoint was 11 mg/kg mg/kg every 24 hours hours IM. (8) Breakpoints were derived from microbiological, PK data (using accepted clinical but extra-label doses), and PD data. The dose of procaine penicillin G modeled was 22 000 U/kg every 24 24 hours IM.

V E T 0 8 , 4 t h e d .

Table 2H Pasteurella multocida


©


Table 2H. Pasteurella multocida (Continued) Test/ Report Group Body Site Macrolides (Continued) Swine (Continued) A Respiratory A Respiratory Phenicols Swine A Respiratory Cattle A Respiratory

Antimicrobial Agent

Disk Content



S

I

R

S

I

R

Tilmicosin Tulathromycin

15 g 30 g

 11

– 15–17

 10

 16

 14

 16

– 32

 32

 18

Florfenicol

30 g

 22

19–21

 18

2

4

8

Florfenicol

30 g

 19

15–18

 14

2

4

8

Chloramphenicol

30 g

 18

13–17

 12

8

16

 32

Comments


 64

(13) For premix product only.

Humans (14) MIC distribution data from canine isolates support these breakpoints for use in canine skin and soft tissue infection; however, efficacy data and PK-PD targets were unavailable.c (15) Warning: Not for food animals.c Tetracyclines Cattle A

Respiratory

Tetracycline

–

–

–

–

2

4

8

(16) Breakpoints were derived from PK data o f oxytetracycline at 20 mg/kg IM, once, and PD data. (17) These breakpoints are applicable only for the injectable formulations. Tetracycline is the class representative.

Swine A

Respiratory

Tetracycline

–

–

–

–

 0.5

1

2

(18) Breakpoints were derived from PK data o f oxytetracycline at 20 mg/kg IM, once, and PD data.

See comment (17). Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton Mueller-Hinton broth; I, intermediate; IM, intramuscularly; intramuscularly; LHB, lysed horse blood; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; PK-PD, pharmacokinetic-pharmacodynamic; QC, quality control; R, resistant; S, susceptible; UTI, urinary tract infection. 8 3

Table 2H Pasteurella multocida

V E T 0 8 , 4 t h e d .


Table 2H Pasteurella multocida 8 4

Table 2H. Pasteurella multocida (Continued) Footnotes a.


b.

Testing and reporting reporting ciprofloxacin ciprofloxacin is is not recommended recommended for any veterinary veterinary species species as PK-PD analysis analysis does not support its use. use.

c.

This comment comment on a human breakpoint breakpoint not found found in CLSI document document M100 M100 2 is added for veterinary application.

V E T 0 8 , 4 t h e d .

References for Table 2H 1

2

Schwarz S, Böttner A, Goossens L, et al. A p roposal of clinical breakpoints for amoxicillin applicable to porcine respiratory tract pathogens. Vet Microbiol . 2008;126(13):178-188. CLSI. Performance CLSI. Performance Standards for Antimicrobial Antimicrobial Susceptibility Susceptibility Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

©





©


8 5


V E T 0 8 , 4 t h e d .


©


Table 2I. Actinobacillu 2I. Actinobacilluss pleuropneumoniae pleuropneumoniae (Continued) (Continued) Test/ Report Antimicrobial Group Body Site Agent Aminoglycosides/Aminocyclitols Horses A Gentamicin

Penicillins Swine A

Respiratory

Ampicillin

Disk Content



S

I

R

S

I

R

Comments

10 g

≥ 16

13–15

≤ 12

≤2

4

≥8

(3) Breakpoints were derived from microbiological, PK data (using accepted clinical doses), and PD data. For horses, the dose of gentamicin modeled was 6.6 mg/kg every 24 hours IM.

–

–

–

–

≤ 0.5

1

≥ 2.0

(4) Ampicillin is the class representative for the aminopenicillins aminopenicillins and should be tested. (5) Breakpoints were derived from microbiological data using ampicillin, PK data from a dose of 15 mg/kg IM of amoxicillin once daily, and PD data. 2

Cephalosporins Swine A Respiratory Fluoroquinolonesb Swine A Respiratory Macrolides Swine A Respiratory

Ceftiofur

30 g

 21

18 – 20 20

 17

2

4

8

Enrofloxacin

5 µg

≥ 23

19–22

≤ 18

≤ 0.25

0.5

≥1

Tulathromycin

30 µg

≥ 10

–

–

≤ 64

–

–

 16

–

≥ 32

 16

–

–

A

Respiratory

Tilmicosin

15 µg

 11

–

≤ 10

A

Respiratory

Tildipirosin

–

–

–

–

(6) Hazy growth or double zones should be ignored. The outer, discrete zone of inhibition should be read. To detect isolates nonsusceptible to tulathromycin, broth microdilution testing is required. (7) Zone diameter breakpoints for disk diffusion testing have not been established. It is recommended to test A. test A. pleuropneumoniae by MIC.

Phenicols Swine 8 7


A

Respiratory

Florfenicol

30 µg

≥ 22

19–21

≤ 18

≤2

4

≥8

(8) For premix product only.

Table 2I Actinobacillus pleuropneumoniae pleuropneumoniae

V E T 0 8 , 4 t h e d .


Table 2I Actinobacillus pleuropneumoniae pleuropneumoniae 8 8

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Table 2I. Actinobacillu 2I. Actinobacilluss pleuropneumoniae pleuropneumoniae (Continued) (Continued) Test/ Report Group Body Site Pleuromutilins Swine A Respiratory

Tiamulin

Tetracyclines Swine A Respiratory

Tetracycline

Antimicrobial Agent

Disk Content



S

I

R

S

I

R

30 µg

9

–

8

 16

–

 32

–

–

–

–

 0.5

1

2

Comments

V E T 0 8 , 4 t h e d .


(10) These breakpoints are applicable only for the injectable formulations. Tetracycline is the class representative. Abbreviations: ATCC®, American Type Culture Collection; I, intermediate; IM, intramuscularly; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; pharmacokinetic; QC, quality control; R, resistant; S, susceptible; susceptible; VFM, veterinary veterinary fastidious medium. medium. Footnotes a.


b.

Testing and reporting reporting ciprofloxacin ciprofloxacin is not recommended recommended for any veterinary veterinary species because because pharmacokinetic-pharmacodyn pharmacokinetic-pharmacodynamic amic analysis does does not support its use. Additionally, isolates that are intermediate or resistant to any fluoroquinolone fluoroquinolone may be at increased risk of developing resistance resistance to all fluoroquinolones. fluoroquinolones.

References for Table 2I 1


2

Schwarz S, Böttner A, Goossens L, et al. A proposal of clinical breakpoints for amoxicillin amoxicillin applicable applicable to porcine respiratory tract pathogens. pathogens. Vet Microbiol . 2008;126(13):178-188.




©


8 9


V E T 0 8 , 4 t h e d .


©


Table 2J. Histophilu 2J. Histophiluss somni (Continued) (Continued) Test/ Report Antimicrobial Group Body Site Agent Aminoglycosides/Aminocyclitols Cattle A Respiratory Spectinomycin

Disk Content



S

I

R

S

I

R

100 g

 14

11 – 13 13

 10

 32

64

≥ 128

Comments


Penicillins Cattle

A

Respiratory Ampicillin

–

–

–

–

≤ 0.03

0.06–0.12

≥ 0.25

A

Respiratory

–

–

–

–

≤ 0.25

0.5

≥1

Ceftiofur

30 g

 21

18 – 20 20

 17

2

4

8

Enrofloxacin

5 µg

≥ 21

17–20

≤ 16

≤ 0.25

0.5–1

≥2

Cephalosporins Cattle A Respiratory

Penicillin G

(3) Breakpoints were derived from microbiological and PK-PD data. The dose of ampicillin ampicillin trihydrate used to derive this breakpoint was 11 mg/kg every 24 hours IM. (4) Breakpoints were derived from microbiological, PK data (using accepted clinical but extra-label doses), and PD data. The dose of procaine penicillin G modeled modeled was 22 000 U/kg every 24 hours IM.

Fluoroquinolonesb Cattle

A Respiratory Macrolides Cattle A Respiratory A A

Gamithromycin

15 µg

≥ 15

12–14

≤ 11

≤4

8

≥ 16

Respiratory

Tildipirosin

60 µg

≥ 17

14–16

≤ 13

8

16

≥ 32

Respiratory

Tulathromycin

30 µg

≥ 18

15–17

≤ 14

≤ 16

32

≥ 64

Respiratory

Florfenicol

30 µg

≥ 19

15–18

≤ 14

≤2

4

≥8

Phenicols Cattle

A

V E T 0 8 , 4 t h e d .

9 1

Table 2J Histophilus somni


Table 2J Histophilus somni 9 2

Table 2J. Histophilu 2J. Histophiluss somni (Continued) (Continued) Test/ Report Group Body Site Tetracyclines

Antimicrobial Agent

Disk Content



S

I

R

S

I

R

–

–

–

≤2

4

≥8

Comments

V E T 0 8 , 4 t h e d .

Cattle

A

Respiratory

Tetracycline

–


(6) These breakpoints and interpretive categories are applicable only for the injectable formulations. Tetracycline is the class representative. Abbreviations: ATCC®, American Type Culture Collection; I, intermediate; IM, intramuscularly; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; pharmacokinetic; PK-PD, pharmacokinetic-pharmacodynam pharmacokinetic-pharmacodynamic; ic; QC, quality quality control; R, resistant; S, susceptible; VFM, VFM, veterinary fastidious medium. medium. Footnotes ©


a.


b.

Testing and reporting reporting ciprofloxacin ciprofloxacin is not recommended for any any veterinary species species because PK-PD analysis does does not support its use. Additionally, isolates isolates that are intermediate or resistant to any fluoroquinolone fluoroquinolone may be at increased risk of developing resistance to all fluoroquinolones.




©


9 3


V E T 0 8 , 4 t h e d .


For Use With VET01

VET08, 4th ed.

s n o i t c e l l o C 3 e e r l u b t a l u T C n i a r t S C Q

Table 3. QC Strain Culture Collection Numbers for Antimicrobial Susceptibility Tests Organism Actinobacillus pleuropneumoniae Enterococcus faecalis E. faecalis E. faecalis Escherichia coli E. coli Histophilus somni somni Klebsiella pneumoniae pneumoniae Mannheimia haemolytica haemolytica Pseudomonas aeruginosa aeruginosa Staphylococcus aureus S. aureus S. aureus S. aureus S. aureus Streptococcus pneumoniae

Equivalent Strain Number for the Indicated Collection ATCC®*1 DSM2 NCTC3 JCM4 CRBIP5 CCUG6 27090 100916T

29212 33186 51299 25922 35218 700025 700603 33396 27853 25923 29213 43300 BAA-976† BAA-977† 49619

2570

12697 12756

7783

1103 5923

12241 11954

5491

1117 1104 2569

10896 12981

6119 2413 2874

103214 100750 104767 76.24 102181 107676

76.110 76.25 103429

9997

17620 30600

17619 17621 15915

104340

Abbreviations: ATCC®, American Type Culture Collection; CCUG, Culture Collection, University of Göteborg, Sweden; CRBIP, Centre de Ressources Biologiques de l’Institut Pasteur; DSM, Deutsche Sammlung von Mikroorganismen und Zellkulturen; JCM, Japan Collection of Microorganisms; NCTC, National Collection of Type Cultures. *

ATCC® is a registered trademark of the American Type Culture Collection. Refer to Table 7F for use of these strains.

†

NOTE: Many of these strains may be available from commercial sources. References for Table 3 1

ATCC. http://www.atcc.org. http://www.atcc.org. Accessed June 5, 2018.

2

DSMZ. http://www.dsmz.de. Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH. Accessed June 5, 2018.

3

Public Health England. National Collection of Type Cultures culturecollections.org.uk/collections/nctc culturecollections.org.uk/collections/nctc.jsp. .jsp. Accessed Jun e 5, 2018.

4

RIKEN BioResource Research Center, Microbe Division, Japan Collection of Microorganisms. JCM On-line catalogue of strains. http://jcm.brc.riken.jp/en/catalogue_e. http://jcm.brc.riken.jp/en/catalogue_e. Accessed June 5, 2018.

5

CRBIP. Centre de Ressources Biologiques de l’Institut Pasteur. https://www.pasteur.fr/en/public-health/crbip. https://www.pasteur.fr/en/public-health/crbip. Accessed June 5, 2018.

6

CCUG. Culture Collection, University of Göteborg, Sweden. http://ccug.se/. Accessed Accessed June 5, 2018.

94

©

(NCTC).

http://www.phe-



For Use With VET01

VET08, 4th ed.


©


95

C L S I V E T 0 1 S G e n e k r s i i c A D d r s m o t i f n s V C e E A T Q T 4 0 e s n 1 l u o i S b o i s 3 a u F T d i N ff t i s D G a e f n n e o r i c N A d m i n V E T 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With VET01 and M02—Disk Diffusion

VET08, 4th ed.

Table 4A. Disk Diffusion QC Ranges for Nonfastidious Organisms Disk Diffusion QC Ranges, mm

Antimicrobial Antimicrobial Agent

Escherichia coli ATCC®a 25922

Disk Content

Amikacin 30 µg 19–26 Amoxicillinclavulanate b 20/10 µg 18–24 Ampicillin 10 µg 15–22 Apramycin 15 µg 15 15–20 Cefazolin 30 µg 21–27 Cefoperazone 30 µg 24–33 Cefovecin 30 µg 25–30 Cefoxitin 30 µg 23–29 Cefpodoxime 10 µg 23–28 Ceftiofur 30 µg 26–31 Cephalothin 30 µg 15 1 5–21 Chloramphenicol 30 µg 21–27 d 2 µg – Clindamycin Danofloxacin 5 µg 29–36 Difloxacin 28–35 10 g Doxycycline 18–24 30 g Enrofloxacin 5 µg 32–40 Erythromycin 15 µg – Florfenicol 22–28 30 g Gamithromycin 15 µg – e 10 µg 19–26 Gentamicin Imipenem 10 µg 26–32 Kanamycin 30 µg 17–25 Kanamycin-cephalexin 30 µg/15 µg 19–25 Marbofloxacin 5 µg 29–37 Minocycline 30 µg 19–25 Neomycin 30 µg 17–23 Orbifloxacin 29–37 10 g Oxacillin 1 µg – Penicillin 10 units – Penicillin-novobiocin (1/3) 10 units/30 µg – Piperacillin 100 µg 24–30 Piperacillin-tazobactam 100 µg/10 µg 24–30 Pirlimycin 2 µg – Pradofloxacin 5 µg 31–39 Rifampin 5 µg 8–10 Spectinomycin 100 µg 21–25 Sulfisoxazolef 300 µg 15–23 Tetracycline 30 µg 18–25 Tiamulin 30 µg – Tildipirosin 60 µg – Tilmicosin 15 µg – TrimethoprimSulfamethoxazolef 1.25/23.75 µg 23–29 Tulathromycin 30 µg – Tylosin 30 µg – Vancomycin 30 µg – ® Abbreviations: ATCC , American Type Culture Collection; QC, quality control.

96

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Staphylococcus Staphylococcus aureus ATCC® 25923

Pseudomonas aeruginosa ATCC® 27853

20–26

18-26

28–36 27–35 17–24 29–35 23–34 25–32 23–29 19–25 27–31c 29–37 19–26 24–30 24–31 27–33 23–29 27–31 22–30 22–29 19–26 19–27 – 19–26 19–25 24–30 25–30 18–26 24–30 18–24 26–37 30–36 – 27–36 19 –25 29–38 26–34 13–17 24–34 24–30 25–32 20–26g 17–21h

– – 13–18 – – – – – 14–18 – – – 18–25 16–22 – 15–19 – – – 17–23 20–28 – – 20–25 – – 16–22 – – – 25–33 25–33 – 21–28 – 10–14 – – – – –

24–32 18–24 18–26 17–21

– – – –




VET08, 4th ed.

Table 4A. (Continued) Footnotes

a.

ATCC® is a registered trademark of the American Type Culture Collection. Per ATCC® convention, the trademark symbol is used after “BAA” in each catalog number, in conjunction with the registered ATCC ® name.

b.

The QC ranges for E. for E. coli ATCC coli ATCC® 35218 for amoxicillin-clavulanate and piperacillin-tazobactam are 17–22 mm and 24– 30 mm, respectively. For modified instructions for QC of -lactam combination combination agents, refer to CLSI document M100 1 Table 4A-2.

c.

The ceftiofur QC range for S. aureus aureus ATCC® 25923 when using Mueller-Hinton agar (MHA) with 5% sheep blood or chocolate MHA is 24–30 mm.

d.

When disk approximation tests are performed with erythromycin and clindamycin, S. aureus ATCC® BAA-977™ (containing inducible ermA-mediated ermA-mediated resistance) and S. aureus ATCC® BAA-976™ (containing msrA-mediated msrA-mediated macrolide-only efflux) are recommended as supplemental QC strains (eg, for training, competence assessment, or test evaluation). S. aureus ATCC aureus ATCC® ® BAA-977™ should demonstrate inducible lincosamide resistance while S. aureus aureus ATCC BAA-976™ should not demonstrate inducible lincosamide resistance. S. aureus ATCC aureus ATCC® 25923 should be used for routine QC (eg, weekly or daily) of erythromycin and clindamycin disks using standard MHA. S. aureus ATCC aureus ATCC® 29213 should be used for routine QC (eg, weekly or daily) of erythromycin and clindamycin minimal inhibitory concentration assays using standard cation-adjusted Mueller-Hinton broth.

e.

For high-level aminoglycoside resistance screening QC ranges for gentamicin 120-mg and streptomycin 300-mg disks, use E. use E. faecalis ATCC® 29212 (gentamicin: 16–23 mm; streptomycin: 14–20 mm).

f.

These agents can be affected by excess levels of thymidine and thymine. See VET01, 2 Subchapter 4.1.1.4 for guidance, should a problem with QC occur.

g.

The tildipirosin QC range for S. aureus ATCC aureus ATCC® 25923 when using MHA with 5% sheep blood is 20–26 mm.

h.

QC ranges for tilmicosin were developed using MHA supplemented with 5% defibrinated sheep blood and incubated aerobically.

NOTE 1: Information in boldface type is new or modified since the previous edition. NOTE 2: The dash (–) indicates that no acceptable range has been established.

thymine, E. faecalis faecalis (ATCC (ATCC® 29212 or 33186) NOTE 3: To determine whether the MHA contains excessive levels of thymine, E. should be tested with trimethoprim, sulfonamide compounds, or trimethoprim-sulfamethoxazole, especially when testing Staphylococcus hyicus or M. haemolytica. haemolytica. An inhibition zone of ≥ 20 mm that is free of fine colonies is acceptable. NOTE 4: Certain veterinary-specific disks may or may not be commercially available. Disks not commercially available may be obtained from pharmaceutical sponsors (see NOTE 6 in Table 1). References for Table 4A 1

CLSI. Performance CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28th Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

2

CLSI. Performance CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Bacteria Isolated From Animals. 5th ed. ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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97

k s i D r s o t f s C e A T 4 Q n e s o l u i b i o a s u T d i ff t i s D a f n o N



VET08, 4th ed.

s t s e T n o i s u ff i D B 4 k s e i l D b r a o T f C Q s u o i d i t s a F

Table 4B. Disk Diffusion QC Ranges for Fastidious Organisms

Antimicrobial Antimicrobial Agent

Disk Content

Streptococcus Streptococcus pneumoniae ATCC®a 49619

Disk Diffusion QC Ranges, mm Mannheimia haemolytica Histophilus somni ATCC® 33396 ATCC® 700025

Ampicillin Cefovecin Cefpodoxime Cefquinome Ceftiofur Cephalothin Chloramphenicol Clindamycinf Danofloxacin Doxycycline Enrofloxacin Erythromycin Florfenicol Gamithromycin Gentamicin Kanamycin-cephalexin

10 µg 30 30–36 – 30 µg 25–31 – 10 µg 28 28–34 – 30 µg 30–38 – 30 µg 32–34 29–39 30 µg 26 26–32 – 30 µg 23–27 – – 2 µg 19–25 5 µg – – 25–34 – 30 g 5 µg – – 15 µg 25–30 – 24–31 – 30 g 15 µg 20–26 18–26 10 µg – – 30 µg/ 13–20 – 15 µg Marbofloxacin 5 µg – – b Oxacillin 1 µg –  12 Penicillin 10 units 24–30 – Penicillin-novobiocin 10 units/ 24–30 – (1/3) 30 µg Pradofloxacin 5 µg – – – Rifampin 5 µg 25–30 Tetracycline 30 µg 27–31 – Tiamulin 30 µg – – Tildipirosin 60 µg – – – Tilmicosin 15 µg – Trimethoprim1.25/23.75 20–28 – sulfamethoxazole µg Tulathromycin 30 µg 16–23 17–25 Vancomycin 30 µg 20–27 – Abbreviations: ATCC®, American Type Culture Collection; QC, quality control.

Actinobacillus Actinobacillus pleuropneumoniae pleuropneumoniae ATCC® 27090

–

–

–

34–43

–

–

33–44 36–46

31–41 34–42

– – –

– – –

26–36

27–36

–

–

32–38

31–38

34–44 18–29 14–22

31–40 14–19 15–19

–

–

30–41

30–40

–

–

35–44

29–36

–

–

–

32–41

–

–

27–33 – 15–24 8–16

23–30 12–19 15–23 8–15

26–32

28–32

16–26

8–18

–

–

Disk Diffusion Testing Conditions for Clinical Isolates and Performance of QC Organism

Streptococcus spp. spp. Pasteurella multocida and M. and M. haemolytica

Medium

Incubation

MHA + 5% defibrinated sheep blood MHA + 5% defibrinated sheep blood

5% CO2; 20–24 hours; 35°C Ambient air; 18–24 hours; 35°C

Comments

Isolates that fail to grow in ambient air should be tested by broth microdilution.

H. somni Chocolate MHA 5% CO 2; 20–24 hours; and A. and A. 35°C leuropneumoniae Abbreviations: MHA, Mueller-Hinton agar; QC, quality control.

98

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VET08, 4th ed.

Table 4B. (Continued) Footnotes

a. b.

ATCC® is a registered trademark of the American Type Culture Collection. Deterioration in oxacillin disk content is best assessed with QC organism diameter of 18–24 mm.

S. aureus

ATCC® 25923, with an acceptable zone

NOTE 1: Information in boldface type is new or modified since the previous edition. NOTE 2: The dash (–) indicates that no acceptable range has been established.

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99

s t s e T n o i s u ff i D B 4 k s e i l D b r a o T f C Q s u o i d i t s a F



VET08, 4th ed.

y c n e u q e r F g n i C t 4 s e e T l b C a T Q n o i s u ff i D k s i D

Table 4C. Disk Diffusion Reference Guide to QC Frequency This table summarizes the suggested QC frequency when modifications modifications are made to antimicrobial susceptibility test ™1 systems (refer to CLSI document EP23 ). It applies only to antimicrobial agents for which satisfactory results have been obtained with either the 15-replicate (3- × 5-day) plan or 20 or 30 consecutive test day plan. Otherwise QC is required each test day.

Test Modification Disks Use new shipment or lot number. Use new manufacturer. Addition of new antimicrobial agent to existing system. Media (prepared agar plates) Use new shipment or lot number. Use new manufacturer. Inoculum preparation Convert inoculum preparation/ standardization to use of a device that has its own QC protocol.

Recommended QC Frequency 15-Replicate Plan or 20- or 30-Day 1 Day 5 Days Plan

Comments

X X X

In addition, perform in-house verification studies.

X X

X

Convert inoculum preparation/ standardization to a method that depends on user technique.

X

Measuring zones Change method of measuring zones.

X

Example: Convert from visual adjustment of turbidity to use of a photometric device for which a QC procedure is provided. Example: Convert from visual adjustment of turbidity to another method that is not based on a photometric device. Example: Convert from manual zone measurements to automated zone reader.

In addition, perform in-house verification studies. Instrument/software Instrument/software (eg, automated zone reader) Software update that affects AST results Repair of instrument that affects AST results X

X

Monitoring all drugs, not just those implicated in software modification. Depending on extent of repair (eg, critical component such as the photographic device), additional testing may be appropriate (eg, 5 days).

Abbreviations: AST, antimicrobial susceptibility testing; QC, q uality control.

NOTE 1: QC can be performed before or concurrent with testing patient isolates. Patient results results can be reported for that day if QC results are within the acceptable limits. NOTE 2: Manufacturers of commercial or in-house-prepared tests should follow their own internal procedures and applicable regulations. NOTE 3: For troubleshooting out-of-range results, refer to Table 4D and VET01, 2 Subchapter 8.8. Additional information is available in Table 3 and Appendix C (eg, QC organism characteristics, QC testing recommendations). recommendations). NOTE 4: Broth, saline, and/or water used to prepare an inoculum does not need routine QC.

100

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VET08, 4th ed.

Table 4C. (Continued) (Continued) References for Table 4C 1

CLSI. Laboratory CLSI. Laboratory Quality Control Based on Risk Management; Approved Guideline. CLSI Guideline. CLSI document EP23-A™. Wayne, PA: Clinical and Laboratory Standards I nstitute; 2011.

2

CLSI. Performance CLSI. Performance Standards for Antimicrobial Disk Disk and Dilution Susceptibility Susceptibility Tests for Bacteria Isolated Isolated From Animals. 5th ed. ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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g n i t o o h s e l b u D o r 4 T e C l b Q a T n o i s u ff i D k s i D

Table 4D. Disk Diffusion Troubleshooting Guide This table provides guidance for troubleshooting and corrective action for out-of-range QC, primarily using antimicrobial susceptibility tests with MHA. Refer to VET01, 1 Chapter 8 and VET01,1 Appendix G for additional information. Out-of-range QC tests are often the result of contamination or the use of an incorrect QC strain; corrective action should first include repeating the test with a pure culture of a freshly subcultured QC strain. If the issue is unresolved, this troubleshooting guide should be consulted regarding additional suggestions for troubleshooting out-of-range QC results and unusual clinical isolate results. In addition, see general corrective action outlined in VET011 and notify manufacturers of potential product problems. General Comment

(1) QC organism maintenance: maintenance: Avoid repeated subcultures. subcultures. Retrieve new QC strain strain from stock. If using lyophilized lyophilized ®a strains, follow the maintenance recommendations of the manufacturer. Store Escherichia Store Escherichia coli ATCC coli ATCC 35218 and ® Klebsiella pneumoniae ATCC pneumoniae ATCC 700603 stock cultures at −60 −60 C or below and prepare working cultures weekly (refer to VET01,1 Subchapter 8.4). Antimicrobial Agent

Aminoglycosides

Amin Aminog ogllycos ycosiides des Aminoglycosides

Aminoglycosides Amoxicillinclavulanate

QC Strain

Any

Any Any Pseudomonas aeruginosa ATCC® 27853 P. aeruginosa ATCC® 27853 E. coli ATCC® 35218

Ampicillin

E. coli ATCC coli ATCC® 35218

-lactam group

Any

Aztreonam K. pneumoniae Cefotaxime ATCC® 700603 Cefpodoxime Ceftazidime Ceftriaxone Cefotaxime-clavulanate K. pneumoniae CeftazidimeATCC® 700603 clavulanate Penicillins Any

Observation

Probable Cause

Zone too small

pH of media too low

Zone Zone too too large arge Zone too small

pH of medi mediaa too too high high Ca++ and/or Mg++ content too high

Zone too large

Ca++ and/or Mg++ content too low Clavulanate is labile. Disk has lost potency.

Zone too small

Comments/Suggested Comments/Suggested Actions

Acceptable pH range= range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acce ccepta ptable ble pH rang rangee = 7.2–7.4 Use alternative lot of media.

Use alternative lot of media. Use alternative lot of disks. Check storage conditions and package integrity. See general comment (1) on QC organism maintenance.

Zone too large (should be no zone—resistant) Zone initially acceptable, but decreases to possibly be out of range over time Zone too large

Spontaneous loss of the plasmid encoding the lactamase Imipenem, clavulanate, and cefaclor are especially labile. Disks have lost potency.

Spontaneous loss of the plasmid encoding the lactamase

See general comment (1) on QC organism maintenance.

Negative ESBL test

Spontaneous loss of the plasmid encoding the lactamase pH of media too low


Zone too large

Peni Peniccilli illins ns Carbenicillin

Any Any P. aeruginosa ATCC® 27853

Zone Zone too too small mall Zone too small

Ticarcillin-clavulanate

E. coli ATCC coli ATCC® 35218

Zone too small

pH of medi edia too too high high QC strain develops resistance after repeated subculture. Clavulanate is labile. Disk has lost potency.

Use alternative lot of disks. Check storage conditions and package integrity.

Acceptable pH range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acce Accept ptaable ble pH rang rangee = 7.2–7.4 See general comment (1) on QC organism maintenance. Use alternative lot of disks. Check storage conditions and package integrity.

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Table 4D. (Continued) Anti Antim micro icrobi bia al Age Agent

Obse Observ rva atio tion

Proba robabl blee Caus Causee

Staphylococcus aureus ATCC aureus ATCC® 25923 S. aureus ATCC® 25923 S. aureus ATCC® 25923

Zone too small

pH of media too low

Zone too large

pH of media too high

Zone too small

pH of media too low

Zone too large


Quinolones

S. aureus ATCC® 25923 Any

Zone too small

pH of media too low

Quin uinolones Tetracyclines

Any Any

Zone too large Zone too large

pH of media too hig high pH of media too low

Tet Tetrac racycl yclines ines Tetracyclines

Any Any Any

Zone one too smal smalll Zone too small

Tetracyclines

Any

Zone too large

Sulfonamides Trimethoprim Trimethoprimsulfamethoxazole Various

Enterococcus Enterococcus faecalis ATCC® 29212

Zone ≤ 20 mm

pH of medi mediaa too high high Ca++ and/or Mg++ content too high Ca++ and/or Mg++ content too low Media too high in thymidine content

Any

Many zones too large

Clindamycin

Clindamycin Macrolides

Macrolides

QC Stra train

Inoculum too light Error in inoculum preparation Media depth too thin MHA nutritionally unacceptable

Various

Any

Many zones too small

Inoculum too heavy Error in inoculum preparation Media depth too thick MHA nutritionally unacceptable

Various

Any

One or more zones too small or too large

Measurement error Transcription error Random defective disk

Various

©

Streptococcus pneumoniae ATCC® 49619

Zones too large Lawn of growth scanty

Disk not pressed firmly against agar Inoculum source plate too old and contains too many nonviable cells. Plate used to prepare inoculum should be 18– 20 hours.


Comm Commeents/ nts/Su Sugg ggeeste sted Acti Actio ons

Acceptable pH range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acceptable pH range= range = 7.2–7.4 Acceptable pH range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acceptable pH range= range = 7.2–7.4 Acceptable pH range= range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acceptable pH range = 7.2–7.4 Acceptable pH range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acce Accept ptab ablle pH rang rangee = 7.2–7.4 Use alternative lot of media. Use alternative lot of media. Use alternative lot of media.

Repeat using McFarland 0.5 turbidity standard or standardizing device. Check expiration date and proper storage if using barium sulfate or latex standards. Use agar with depth approximately 4 mm. Recheck alternate lots of MHA. Repeat using McFarland 0.5 turbidity standard or standardizing device. Check expiration date and proper storage if using barium sulfate or latex standards. Use agar with depth approximately 4 mm. Recheck alternate lots of MHA. Recheck readings for measurement or transcription errors. Retest. If retest results out of range and no errors are detected, initiate corrective action. Subculture QC strain and repeat QC test, or retrieve new QC strain from stock.

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Table 4D. (Continued) Antimicrobial Agent

Various

Various

QC Strain

Any

Any

Observation

One QC strain is out of range, but other QC organism(s) is in range with the same antimicrobial agent.

Two QC strains out of range with the same antimicrobial agent. Zones ov overlap

Probable Ca Cause

One QC organism may be a better indicator of a QC problem.

Comments/Suggested Ac Actions

Retest this strain to confirm reproducibility of acceptable results. Evaluate with alternative strains with known MICs.

A pro probl blem em with with the the dis disk k

Initiate corrective action with problem QC strain/antimicrobial strain/antimicrobial agent(s). Use Use alt alter erna nati tive ve lot lot of of dis disks ks..

Check storage conditions and package integrity. Various Any Too ma many di disks pe per pl plate Place no no mo more th than 12 12 di disks on on a 150-mm plate and 5 disks on a 100-mm plate; for some fastidious bacteria that produce large zones, use fewer. ® Abbreviations: ATCC , American Type Culture Collection; ESBL, extended-spectrum -lactamase; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; pH, negative logarithm of hydrogen ion concentration; QC, quality control. Footnote

a.


Reference for Table 4D 1

104

CLSI. Performance CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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s t s e T C I M r o A f 5 C e Q l b s a T u o i d i t s a f n o N

Table 5A. MIC QC Ranges for Nonfastidious Organisms

Antimicrobial Agent

MIC QC Ranges, g/mL Escherichia Enterococcus Enterococcus faecalis coli ATCC® 29212 ATCC® 25922

Staphylococcus Staphylococcus aureus ATCC®a 29213

Pseudomonas Pseudomonas aeruginosa ATCC® 27853

Amikacin 1–4 64–256 0.5–4 1–4 Amoxicillin0.12/0.06– 0.25/0.12– 2/1–8/4 – 0.5/0.25 1.0/0.5 clavulanate b Ampicillin 0.5–2 0.5–2 2–8 – Apramycin 2–8 2– – 2–16 2–16 – – Avilamycin – 0.5–2 Cefazolin 0.25–1 – 1–4 – Cefoperazone 1–4 – 0.12–0.5 2–8 Cefoxitin 1–4 – 2–8 – Cefovecin 0.5–2 – 0.5–2 512–2048 Cefpodoxime 1–8 – 0.25–1 – Ceftiofur 0.25–1.0 – 0.25–1 16–64 – Cephalexin 1–8 – 4–16 Cephalothin 0.12–0.5 – 4–16 – Chloramphenicol 2–16 4–16 2–8 – 0.06–0.25 4–16 – – Clindamycinc Danofloxacin 0.06–0.25 0.25–1 0.008–0.06 0.5–2 Difloxacin 0.06–0.5 1–4 0.015–0.12 1–8 Doxycycline 0.12–0.5 8–32 0.5–2 – Enrofloxacin 0.03–0.12 0.12–1 0.008–0.03 1–4 0.25–1 1–4 – – Erythromycinc Florfenicol 2–8 2–8 2–8 – Gamithromycin 0.5–4 4–32 – – 0.12–1 4–16 0.25–1 0.5–2 Gentamicind Imipenem 0.015–0.06 0.5–2 0.06–0.25 1–4 Kanamycin 1–4 16–64 1–4 – Kanamycin-cephalexin 1/0.1–4/0.4 – 2/0.2–8/0.8 – Marbofloxacin 0.12–0.5 0.5–2 0.008–0.03 0.5–2 Minocycline 0.06–0.5 1–4 0.25–1 – Monensin 2–16 4–16 – – Narasin 0.25–2 0.25–1 – – Orbifloxacin 0.25–2 1–8 0.015–0.12 2–16 Oxacillin 0.12–0.5 8–32 – – Penicillin 0.25–2 1–4 – – Penicillin-novobiocin 0.015/0.03–0.06/0.12 0.25/0.5–2/4 ≥ 8/16 – Piperacillin 1–4 1–4 1–4 1–8 0.25/4–2/4 1/4–4/4 1/4–4/4 1/4–8/4 Piperacillin-tazobactamb Pirlimycin 0.25–1.0 2–8 – – Pradofloxacin 0.03–0.12 0.12–0.5 0.008–0.03 0.25–1 Rifampin 0.004–0.015 0.5–4 4–16 16–64 Spectinomycin 64–256 64–256 8–64 ≥ 256 32–128 32–128 8–32 – Sulfisoxazolee Tetracycline 0.12–1 8–32 0.5–2 8–32 Tiamulin 0.5–2 – – – Tildipirosin 2–16 2– – 1–8 – Tilmicosin 1–4 8–32 – – Trimethoprim8/152–32/608  0.5/9.5  0.5/9.5  0.5/9.5 sulfamethoxazolee Tulathromycin 2–8 4–32 – – Tylosin 0.5–4 0.5–4 – – 0.5–2 1–4 – – Vancomycinf Abbreviations: ATCC®, American Type Culture Collection; MIC, minimal inhibitory concentration; QC, quality control.

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Table 5A. (Continued) Footnotes

a.

ATCC® is a registered trademark of the American Type Culture Collection. Per ATCC® convention, the trademark symbol is used after “BAA” in each catalog number, in conjunction with the registered ATCC ® name.

b.

The QC ranges for E. coli ATCC coli ATCC® 35218 for amoxicillin-clavulanate and piperacillin-tazobactam piperacillin-tazobactam are 4/2 to 16/8 g/mL and 0.5/4 to 2/4 g/mL, respectively. For modified instructions for QC of -lactam combination agents, refer to CLSI document M100,1 Table 5A-2.

c.

When the erythromycin/clindamycin combination well for detecting inducible clindamycin resistance is used, S. aureus ATCC® BAA-977™ (containing inducible ermA-mediated resistance) and S. aureus ATCC® 29213 or S. aureus ATCC® BAA-976™ (containing msrA -mediated macrolide-only efflux) are recommended for QC purposes. S. aureus ATCC® BAA-977™ should demonstrate inducible clindamycin resistance (ie, growth in the well), whereas S. aureus ATCC® 29213 and S. aureus ATCC® BAA-976™ should not demonstrate inducible clindamycin resistance (ie, no growth in the well).

d.

For control organisms for gentamicin gentamicin and streptomycin high-level aminoglycoside resistance detection tests for enterococci, see Table 7G.

e.

These agents can be affected by excess levels of thymidine and thymine. See VET01, 2 Subchapter 8.5.1 for guidance, should a problem with QC occur.

f.

For QC organisms for vancomycin screen test for enterococci, see Table 7G.

NOTE 1: Information in boldface type is new or modified since the previous edition. NOTE 2: The dash (–) indicates that no acceptable range has been established. References for Table 5A 1

CLSI. Performance CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28th Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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Table 5B. MIC QC Ranges for Fastidious Organisms (Broth Dilution Methods) s t s e T C I M B r 5 f o e l b C a Q T s u o i d i t s a F

Antimicrobial Agent

Streptococcus Streptococcus pneumoniae ATCC®a 49619

Mannheimia haemolytica ATCC® 33396

Histophilus somni somni ATCC® 700025

Actinobacillus Actinobacillus pleuropneumoniae pleuropneumoniae ATCC® 27090

Amoxicillin0.03/0.015– – – – clavulanate 0.12/0.06 Ampicillin 0.06–0.25 – – – Cefovecin 0.12–0.5 – 0.001–0.008 0.008–0.03 Cefpodoxime 0.03–0.12 – 0.002–0.008 0.004–0.03 – Cefquinome 0.015–0.06 0.0005–0.004 0.004–0.016 Ceftiofur 0.12–0.5 – – – – Cephalothin 0.5–2 – – Chloramphenicol 2–8 – – – Clindamycin 0.03–0.12 – – – Danofloxacin – – 0.016–0.12 0.03–0.12 Doxycycline 0.016–0.12 – – – Enrofloxacin – – 0.016–0.06 0.016–0.06 – Erythromycin 0.03–0.12 Florfenicol 1–4 – 0.12–0.5 0.25–1 – Gamithromycin 0.03–0.12 0.25–1 2–8 Gentamicin – – 8–32 8–32 Imipenem 0.03–0.12 – – – Kanamycin-cephalexin 64/6.4 – – – – Marbofloxacin – 0.016–0.12 0.016–0.06 – Penicillin 0.25–1 0.016–0.06 0.12–1 Pradofloxacin – – 0.004–0.03 0.004–0.016 Rifampin 0.015–0.06 – – – – Tetracycline 0.06–0.5 0.12–1 0.25–2 Tiamulin 0.5–4 – – 8–32 – Tildipirosin – 2–8 2–16 Tilmicosin – – 2–16 4–32 Trimethoprim0.03/0.57– – 0.12/2.4–1/19 0.016/0.28–0.06/1.14 sulfamethoxazole 0.125/2.38 Tulathromycin 0.12–1 2–8 4–32 16–64 Vancomycin 0. 0.12–0.5 – – – Abbreviations: ATCC®, American Type Culture Collection; MIC, minimal inhibitory concentration; QC, quality control.

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Table 5B. (Continued) s t s e T C I M B r 5 f o e l b C a Q T s u o i d i t s a F

MIC Testing Conditions for Clinical Isolates and Performance of QC Organism

Method

Staphylococcus hyicus

Broth microdilution


Broth microdilution Agar dilution

Pasteurella multocida and M. and M. haemolytica

Broth microdilution

H. somni and A. pleuropneumoniae

Broth microdilution

Agar dilution

Agar dilution

Medium

Incubation

CAMHB + thymidine phosphorylase (0.2 IU/mL) CAMHB + LHB (2.5% to 5% v/v)

Ambient air; 18–24 hours; 35°C

MHA + 5% defibrinated sheep blood CAMHBb

5% CO2; 20–24 hours; 35°C

MHA + 5% defibrinated sheep blood VFM

Comments

For testing sulfonamides and trimethoprim only. 1

Ambient air; 20–24 hours; 35°C

18–24 hours; 35ºC

18–24 hours; 35ºC

Isolates tested by agar dilution that fail to grow in ambient air should be tested by broth microdilution.

5% CO2; 20–24 hours; 35°C

Chocolate MHA

5% CO2; 20–24 hours; 35°C Abbreviations: CAMHB, cation-adjusted Mueller-Hinton Mueller-Hinton broth; IU, international unit(s); LHB, lysed h orse blood; MHA, MuellerHinton agar; MIC, minimal inhibitory concentration; QC, quality control; VFM, veterinary fastidious medium. Footnotes

a. b.

ATCC® is a registered trademark of the American Type Culture Collection. Strains of M. of M. haemolytica that haemolytica that fail to grow in CAMHB may be retested using the reference method for Streptococcus spp. Streptococcus spp. ® (which incorporates 2.5% to 5% LHB) and S. pneumoniae ATCC pneumoniae ATCC 49619.

NOTE 1: Information in boldface type is new or modified since the previous edition. NOTE 2: To determine whether the MHA contains excessive levels of thymidine or thymine, E. faecalis (ATCC faecalis (ATCC® 29212 or 33186) should be tested with trimethoprim, sulfa compounds, or trimethoprim-sulfamethoxazole, trimethoprim-sulfamethoxazole, especially when testing S. hyicus or hyicus or M. M. haemolytica. If haemolytica. If excessive thymidine is present, an expected MIC within the susceptible category (trimethoprim-sulfamethoxazole (trimethoprim-sulfamethoxazole MIC  0.5/9.5 µg/mL) will shift to the resistant category (trimethoprimsulfamethoxazole MIC > 4/76 µg/mL). NOTE 3: The dash (–) indicates that no acceptable range has been established. Reference for Table 5B 1

Wegener HC, Watts JL, Salmon SA, Yancey RJ Jr. Antimicrobial susceptibility testing of Staphylococcus hyicus isolated hyicus isolated from exudative epidermitis in pigs. J pigs. J Clin Microbiol . 1994;32(3):793-795.

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C L S I V E T 0 1 S n G o i e t n e u l r i i c D A r d m a g i n A V C r E T 5 o 1 f 1 0 e 1 l C S b M Q 3 a F T C N I G M e e n b e o r i r c A e d a m n i A n V E T 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With M11

VET08, 4th ed.

Table 5C. MIC QC Ranges for Anaerobes (Agar Dilution Method1) MIC QC Ranges (g/mL) Clostridioides ( formerly formerly Bacteroides Bacteroides Eubacterium Clostridium) Clostridium) Bacteroides Bacteroides fragilis thetaiotaomicron lentum difficile ®a ® ® Antimicrobial Antimicrobial Agent ATCC 25285 ATCC 29741 ATCC 43055 ATCC® 700057 Avilamycin – – – 0.125–0.5 Cefovecin 8–32 16–128 – – Ceftiofur 32–256 64–256 – – Monensin – – – 1–8 Narasin – – – 0.25–2 Pradofloxacin 0.06–0.25 0.5–2 0.12–0.5 – Tilmicosin – – – 0.25–1 Tylosin – – – 0.125–0.5 ® Abbreviations: ATCC , American Type Culture Collection; MIC, minimal inhibitory concentration; QC, quality control. Footnote

a.


Reference for Table 5C 1

110

CLSI. Methods CLSI. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard—Eighth Edition. Edition. CLSI document M11-A8. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.

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C L S I V E T 0 1 n S o i t G u l e i n d e o r r i c c A i d M m i h n t V o E D r T 5 B 0 e 1 1 l r 1 S b o f M 3 a F T C N Q G C I e n M e r i e c b A d o r m e i n a V n E A T 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With M11

VET08, 4th ed.

Table 5D. MIC QC Ranges for Anaerobes (Broth Microdilution Method1) MIC QC Ranges ( g/mL) Clostridioides (formerly Bacteroides Bacteroides Eubacterium Clostridium) Clostridium) Bacteroides Bacteroides fragilis thetaiotaomicron lentum difficile Antimicrobial Antimicrobial Agent ATCC®a 25285 ATCC® 29741 ATCC® 43055 ATCC® 700057 Avilamycin – – – 0.03–0.25 Cefovecin 8–32 8– 16–64 – – Ceftiofur 8–64 32–128 – 64–512 Pradofloxacin 0.06–0.25 0.5–2 0.12–0.5 – ® Abbreviations: ATCC , American Type Culture Collection; MIC, minimal inhibitory concentration; QC, quality control. Footnote

a.


Reference for Table 5D 1

112

CLSI. Methods CLSI. Methods for Antimicrobial Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Bacteria; Approved Standard—Eighth Standard—Eighth Edition. Edition. CLSI document M11-A8. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.

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Table 5E. MIC Reference Guide to QC Frequency y c n e u q e r E F 5 g e n l b i t a s e T T C Q C I M

This table summarizes the suggested QC frequency when modifications are made to antimicrobial susceptibility test systems (refer to CLSI document EP23 ™1). It applies only to antimicrobial agents for which satisfactory results have been obtained with either the 15-replicate (3- × 5-day) plan or 20 or 30 consecutive test day plan. Otherwise QC is required each test day.

Test Modification MIC tests(s) Use new shipment or lot number. Expand dilution range.

Reduce dilution range.

Recommended QC Frequency 15-Replicate Plan or 20- or 30-Day 1 Day 5 Days Plan

X X

X

Use new method (same company).

X

Use new manufacturer of MIC test. Use new manufacturer of broth or agar. Addition of new antimicrobial agent to existing system Inoculum preparation Convert inoculum preparation/ standardization to use of a device that has its own QC protocol.

X

Example: Convert from breakpoint to expanded range MIC panels. Example: Convert from expanded dilution range to breakpoint panels. Examples: Convert from overnight to rapid MIC test.

In addition, perform in-house verification studies. In addition, perform in-house verification studies.

X X

X

Convert inoculum preparation/ standardization to a method that is dependent on user technique. Instrument/software Software update that affects AST results Repair of instrument that affects AST results

Comments

X

In addition, perform in-house verification studies. Example: Convert from visual adjustment of turbidity to use of a photometric device for which a QC procedure is provided. Example: Convert from visual adjustment of turbidity to another method that is not based on a photometric device.

Monitor all drugs, not just those implicated in software modification. Depending on extent of repair (eg, critical component such as the photographic device), X additional testing may be appropriate (eg, 5 days). Abbreviations: AST, antimicrobial susceptibility testing; MIC, minimal inhibitory concentration; QC, quality control. X

NOTE 1: QC can be performed before or concurrent with testing patient isolates. Patient results can be reported for that day if QC results are within the acceptable limits. NOTE 2: Manufacturers of commercial or in-house-prepared tests should follow their own internal procedures and applicable regulations. NOTE 3: Acceptable MIC QC limits for regulatory agency–cleared antimicrobial susceptibility tests may differ slightly from acceptable CLSI QC limits. Users of each device should use the manufacturer’s procedures and QC limits as indicated in the instructions for use. NOTE 4: For troubleshooting out-of-range results, refer to VET01,2 Subchapter 8.8 and VET08 Table 5F. Additional information is available in Table 3 and Appendix C (eg, organism characteristics, QC testing recommendations). NOTE 5: Broth, saline, and/or water used to prepare an inoculum does not need routine QC.

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Table 5E. (Continued) References for Table 5E 1

CLSI. Laboratory CLSI. Laboratory Quality Control Based on Risk Management; Management; Approved Guideline. Guideline. CLSI document EP23-A™. Wayne, PA: Clinical and Laboratory Standards Institute; 2011.

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Table 5F. MIC Troubleshooting Guide g n i t o o h F s e 5 l e b l b u a o r T T C Q C I M

This table provides guidance for troubleshooting and corrective action for out-of-range QC, primarily using CAMHB for broth microdilution. Refer to VET01, 1 Chapter 8 and VET01, 1 Appendix G for additional information. Out-ofrange QC tests are often the result of contamination or the use of an incorrect QC strain; corrective action should first include repeating the test with a pure culture of a freshly subcultured QC strain . If the issue is unresolved, this troubleshooting guide should be consulted regarding additional suggestions for troubleshooting outof-range QC results and unusual clinical isolate results. In addition, see general corrective action outlined in VET011 and notify manufacturers of potential product problems. General Comment

(1) QC organism maintenance: maintenance: Avoid repeated subcultures. Retrieve Retrieve new QC strain from from stock. If using lyophilized strains, follow the maintenance recommendations of the manufacturer. Store Escherichia Store Escherichia coli ATCC coli ATCC®a 35218 and Klebsiella pneumoniae ATCC pneumoniae ATCC® 700603 stock cultures at −60 −60 C or below and prepare working cultures weekly (refer to VET01, 1 Subchapter 8.4). Antimicrobial Agent

Aminoglycosides

Aminoglycosides Aminoglycosides

Aminoglycosides Amoxicillinclavulanate

-lactam group

Aztreonam Cefotaxime Cefpodoxime Ceftazidime Ceftriaxone Cefotaximeclavulanate Ceftazidimeclavulanate Carbapenems Carbapenems

QC Strain

Any

Any Pseudomonas aeruginosa ATCC® 27853 P. aeruginosa ATCC® 27853 E. coli ATCC® 35218

Any

K. pneumoniae ATCC® 700603

Observation

Probable Cause

Comments/Suggested Actions

MIC too high

pH of media too low

MIC too low MIC too high

pH of media too high Ca++ and/or Mg++ content too high

Acceptable pH range= range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acceptable pH range = 7.2–7.4 Acceptable range = Ca++ 20–25 mg/L Mg++ 10–12.5 mg/L

MIC too low

Ca++ and/or Mg++ content too low Clavulanate is labile.

Acceptable range = Ca++ 20–25 mg/L Mg++ 10–12.5 mg/L Use alternative lot.

Antimicrobial agent is degrading. Imipenem, cefaclor, and clavulanate are especially labile. Antimicrobial agents are degrading.

Check storage and package integrity. Use alternative lot.

Spontaneous loss of the plasmid encoding the lactamase


MIC too high

MIC initially acceptable, but increases to possibly be out of range over time MIC too low

Check storage and package integrity.

K. pneumoniae ATCC® 700603

Negative ESBL test

Spontaneous loss of the plasmid encoding the lactamase.


P. aeruginosa ATCC® 27853 P. aeruginosa ATCC® 27853

MIC too high

Zn++ concentration in media is too high. Antimicrobial agent is degrading.

Use alternative lot.

MIC too high

Use alternative lot. Check storage and package integrity. Repeated imipenem results at the upper end of QC range with P. with P. aeruginosa ATCC® 27853 may indicate deterioration of the drug.

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Table 5F. (Continued) Antimicrobial Agent

QC Strain

Observation

Probable Cause


Penicillins

Any

MIC too low

pH of media too low

Penicillins Carbenicillin

Any P. aeruginosa ATCC® 27853

MIC too high MIC too high

Ticarcillinclavulanate

E. coli ATCC® 35218

MIC too high

pH of media too high QC strain develops resistance after repeated subculture. Clavulanate is labile.

MIC too high

Check storage and package integrity. Acceptable pH range= range = 7.2–7.4 Avoid CO2 incubation, which lowers pH.

MIC too low


Acceptable pH range= range = 7.2–7.4

Quinolones

S. aureus ATCC® 29213 E. faecalis ATCC® 29212 S. aureus ATCC® 29213 E. faecalis ATCC® 29212 Any

Antimicrobial agent is degrading. pH of media too low

MIC too high

pH of media too low

Quinolones Tetracyclines Tetracyclines

Any Any Any

MIC too low MIC too low MIC too high

pH of media too high pH of media too low pH of media too high

Tetracyclines

Any

MIC too high

Tetracyclines

Any

MIC too low

Various

Any

Many MICs too low

Ca++ and/or Mg ++ content too high Ca++ and/or Mg ++ content too low Inoculum too light; error in inoculum preparation

Various

Any

Various

Any

Many MICs too high or too low Many MICs too high

Acceptable pH range= range = 7.2–7.4. Avoid CO2 incubation, which lowers pH. Acceptable pH range = 7.2–7.4 Acceptable pH range = 7.2–7.4 Acceptable pH range= range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acceptable range = Ca++ 20–25 mg/L Mg++ 10–12.5 mg/L Acceptable range = Ca++ 20–25 mg/L Mg++ 10–12.5 mg/L Repeat using McFarland 0.5 turbidity standard or standardizing device. Check expiration date and proper storage if using barium sulfate or latex standards. Check steps in inoculum preparation and inoculation procedure. Perform colony count check of growth control well immediately after inoculation and before incubation ( E. E. coli ATCC coli ATCC® 25922 closely approximates 5 × 10 5 CFU/mL). Use alternative lot.

Clindamycin Macrolides Ketolides Clindamycin Macrolides Ketolides

©

CAMHB not optimal Inoculum too heavy


Acceptable pH range = 7.2–7.4 Avoid CO2 incubation, which lowers pH. Acceptable pH range = 7.2–7.4 See general comment (1) on QC organism maintenance. Use alternative lot.

Repeat using McFarland 0.5 turbidity standard or standardizing device. Check expiration date and proper storage if using barium sulfate or latex standards. Check steps in inoculum preparation and inoculation procedure. Perform colony count check of growth control well immediately after inoculation and before incubation ( E. E. coli ATCC coli ATCC® 25922 closely approximates 5 × 10 5 CFU/mL).

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VET08, 4th ed.

Table 5F. (Continued) g n i t o o h F s e 5 l e b l b u a o r T T C Q C I M

Antimicrobial Agent

Various

QC Strain

Any

Observation

Skipped wells

Probable Cause


Contamination.

Repeat QC test.

Improper inoculation of panel or inadequate mixing of inoculum.

Use alternative lot.

Actual concentration of drug in wells inaccurate.

Various

Various

Any

S. pneumoniae ATCC® 49619

Volume of broth in wells inaccurate. Possible reading/transcription error

Many MICs too high or too low MICs too low

Inoculum source plate too old and contains too many nonviable cells. Plate used to prepare inoculum should be 18–20 hours.

Various

Any

QC results from one strain are out of range, but QC results from other strains are in range with the same antimicrobial agent.

Various

Any

QC results from two strains are out of range with the same antimicrobial agent. One QC result out of range, but the antimicrobial agent is not an agent reported for patient results (eg, not on hospital formulary).

Various

Indicates a problem with the antimicrobial agent.

Use alternative lot. Subculture QC strain and repeat QC test; or subculture new QC strain from stock culture. Use alternative lot.

Determine if the in-range QC strain has an on-scale end point for the agent in question. Retest this strain to confirm reproducibility of acceptable results. Evaluate with alternative strains with known MICs. Initiate corrective action with problem QC strain/antimicrobial strain/antimicrobial agent(s). Initiate corrective action.

May be a systemic problem.

If antimicrobial agent is not normally reported, no repeat is necessary if adequate controls are in place to prevent reporting of the out-of-range antimicrobial agent. Carefully check antimicrobial agents of the same class for similar trend toward out-of-control results. If the antimicrobial agent in question is consistently out of control, contact the manufacturer. Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton broth; CFU, colonyforming unit(s); ESBL, extended-spectrum -lactamase; LHB, lysed horse blood; MHB, Mueller-Hinton broth; MIC, minimal inhibitory concentration; QC, quality control.

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Any

MHB with LHB not optimal. One QC organism may be a better indicator of a QC problem (eg, P. (eg, P. aeruginosa ATCC aeruginosa ATCC® 27853 is a better indicator of imipenem deterioration than E. than E. coli ATCC coli ATCC® 25922).

Recheck readings.

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For Use With VET01

VET08, 4th ed.

Table 5F. (Continued) (Continued) Footnote

a.

ATCC® is a registered trademark o f the American Type Culture Collection.

Reference for Table 5F 1

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VET08, 4th ed.

Table 6. Solvents and Diluents D iluents for Preparing Stock Solutions of Antimicrobial An timicrobial Agents Antimicrobial Agent s t n e u l i 6 D e d l b n a a s T t n e v l o S

Amikacin Amox Amoxic icil illi lin, n, clav clavul ulan anat atee Ampici picill lliin Avilamycin Cefazo fazoli lin n Cefpodoxime

Cephalexin Cephalothinc Chloramphenicol, erythromycin,d florfenicol, tylosin, tilmicosin Difloxacin

Solventa Unless otherwise stated, use a minimum amount of the listed solvent to solubilize the antimicrobial powder. Water Phos Phosph phat atee buff buffer er,, pH 6, 0.1 0.1 mol/ mol/L L Phosp hospha hatte buf buffer, er, pH 8, 0.1 0.1 mol/ ol/L b Methanol Phosp hospha hatte buf buffer, fer, pH 6, 0.1 0.1 mol/L ol/L 0.10% (11.9 mmol/L) aqueous sodium bicarbonate Phosphate buffer, pH 6, 0.1 mol/L Phosphate buffer, pH 6, 0.1 mol/L 95% ethanol

Gentamicin Imipenem

1/2 volume of water, then add NaOH dropwise to dissolve Water 1/2 volume of water, then add 1 mol/L NaOH dropwise to dissolve Phosphate buffer, pH 6, 0.2 mol/L with the aid of ultrasonication Water Phosphate buffer, pH 7.2, 0.01 mol/L

Kanamycin Minocycline Monensin Narasin Nitrofurantoin Nitrofurantoine

Water Water Methanol b Methanol b Phosphate buffer, pH 8, 0.1 mol/L

Orbifloxacin

1/2 volume of water, then add 1 mol/L NaOH dropwise to dissolve Water 1/2 volume of water, then add 1 mol/L NaOH dropwise to dissolve Methanol b (maximum concentration = 640 μg/mL) 1/2 volume hot water and minimal amount of 2.5 mol/L NaOH to dissolve Water Water Phosphate buffer, pH 6, 0.1 mol/L

Doxycycline Enrofloxacin

Gamithromycin Gamithromycin

Piperacillin Pradofloxacin

Rifampin Sulfonamides Tazobactam Tetracycline Tildipirosin Tildipirosin

Trimethoprim Tulathromycinf Vancomycin

0.05 mol/L lactic b or hydrochloric acid, b 10% of final volume 0.015 M citric acid Water

Diluenta Finish diluting the final stock solution as stated below. Water Phos Phosph phat atee buff buffer er,, pH 6, 0.1 0.1 mol/ mol/L L Phosp hospha hatte buf buffer, fer, pH 6, 0.1 0.1 mol/L ol/L b Methanol Phos Phosph phat atee buff uffer, er, pH 6, 0.1 0.1 mol/L ol/L Water

Water Water Water

Water Water Water

Water Water Phosphate buffer, pH 7.2, 0.01 mol/L Water Water Methanol b Methanol b Phosphate buffer, pH 8, 0.01 mol/L Water Water Water

Water (with stirring) Water Water Water Phosphate buffer, pH 8, 0.1 mol/L Water (may need heat)

Water (may need heat) Water

Abbreviation: pH, negative logarithm of hydrogen ion concentration.

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Table 6. (Continued) Footnotes

a.

These solvents and diluents can be further diluted as necessary in in water or broth. The products known to to be suitable suitable for water water solvents and diluents are amikacin, carbenicillin, cefquinome, ciprofloxacin, clindamycin, gentamicin, kanamycin, methicillin, novobiocin, oxacillin, penicillin, pirlimycin, tetracyclines, tiamulin (if hydrogen fumarate), trimethoprim (if lactate), and vancomycin.

b.

Consult the safety data data sheets before working with with any antimicrobial reference standard powder, solvent, solvent, or diluent. Some of the compounds (eg, solvents such as dimethyl sulfoxide [DMSO], methanol) are more toxic than others and may necessitate handling in a chemical fume hood.

c.

All other cephalosporins and cephems except except ceftiofur and cefquinome not listed above are solubilized (unless otherwise indicated by the manufacturer) in phosphate buffer, pH 6, 0.1 mol/L, and further diluted in sterile distilled water. Ceftiofur can be solubilized in water or broth.

d.

Solvent can also be glacial acetic acetic acid: use 1/2 volume of water, water, then add glacial glacial acetic acetic acid dropwise until dissolved, not to exceed 2.5 µL/mL.

e.

Alternatively, nitrofurantoin, tylosin, tylosin, and and tilmicosin tilmicosin can be dissolved in DMSO. DMSO.

f.

Tulathromycin needs needs an equilibrated stock solution. The procedure for producing an equilibrated equilibrated solution is provided with technical grade powder by the sponsor (refer to Table 1 for sponsor contact information).

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s L B S E r o f s t A 7 s e e T l b n a o T i s u ff i D k s i D

Table 7A. Disk Diffusion Tests for Extended-Spectrum -Lactamases in Klebsiella pneumoniae, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia oxytoca, Escherichia coli, and Proteus and Proteus mirabilis Test Medium Antimicrobial disk concentration

Criteria for Performance of ESBL Test a

MHA For K. For K. pneumoniae, K. oxytoca, oxytoca, and E. and E. coli: Cefpodoxime Ceftazidime Aztreonam Cefotaxime Ceftriaxone For P. For P. mirabilis b: Cefpodoxime Ceftazidime Cefotaxime

10 g 30 g 30 g 30 g 30 g

or or or or

ESBL Test a

MHA Ceftazidime Ceftazidime-clavulanatec and Cefotaxime Cefotaxime-clavulanatec

10 g or 30 g or 30 g

30 g 30/10 g

30 g 30/10 g

(Testing necessitates using both cefotaxime and ceftazidime, alone and in combination with clavulanate.)

(Testing more than one antimicrobial agent improves the sensitivity of ESBL detection.) Inoculum

Standard disk diffusion procedure

Standard disk diffusion procedure

Incubation conditions

35°C ± 2°C; ambient air


Incubation Incubatio n length

16–18 hours

16–18 hours

For K. For K. pneumoniae, K. oxytoca, oxytoca, and E. and E. coli:  17 mm Cefpodoxime zone  22 mm Ceftazidime zone  27 mm Aztreonam zone  27 mm Cefotaxime zone  25 mm Ceftriaxone zone

A  5-mm increase in a zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone = ESBL (eg, ceftazidime zone = 16; ceftazidime-clavulanate ceftazidime-clavulanate zone = 21).

For P. For P. mirabilis b: Cefpodoxime zone Ceftazidime zone Cefotaxime zone

For all confirmed ESBL-producing strains, see reporting recommendations in CLSI document M100,1 Table 3A.

Results

 22 mm  22 mm  27 mm

Zones above may indicate ESBL pr oduction. QC recommendations recommendations

When testing antimicrobial agents for ESBL detection, K. pneumoniae ATCCd 700603 is provided as a supplemental QC strain (eg, for training, competence assessment, or test evaluation). Either strain, K. strain, K. pneumoniae ATCC pneumoniae ATCC 700603 or E. or E. coli ATCC 25922, may then be used for routine QC (eg, weekly or daily). ®

E. coli ATCC 25922 (see acceptable QC ranges in Table 4 A) K. pneumoniae ATCC pneumoniae ATCC® 700603: 9–16 mm Cefpodoxime zone 10–18 mm Ceftazidime zone 9–17 mm Aztreonam zone 17–25 mm Cefotaxime zone 16–24 mm Ceftriaxone zone

When performing the ESBL tests, K. tests, K. pneumoniae ATCC pneumoniae ATCC 700603 and E. coli ATCC coli ATCC 25922 should be used for routine QC (eg, weekly or daily). Acceptable QC:

E. coli ATCC® 25922:  2-mm increase in zone diameter for antimicrobial agent tested in combination with clavulanate vs the zone diameter when tested alone.

K. pneumoniae ATCC pneumoniae ATCC® 700603:  5-mm increase in zone diameter of ceftazidimeclavulanate vs ceftazidime alone;  3-mm increase in zone diameter of cefotaxime-clavulanate cefotaxime-clavulanate vs cefotaxime alone. ® Abbreviations: ATCC , American Type Culture Collection; ESBL, extended-spectrum -lactamase; MHA, Mueller-Hinton agar; QC, quality control.

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Table 7A. (Continued) Footnotes a.

Following evaluation of pharmacokinetic-pharmacody pharmacokinetic-pharmacodynamic namic properties, limited clinical data, and minimal inhibitory concentration distributions distributions for human antimicrobial susceptibility testing data by the Subcommittee on Antimicrobial Antimicrobial Susceptibility Testing, revised breakpoints for cefazolin, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, and aztreonam were published in January 2010 and are listed in CLSI document M100, 1 Table 2A. Cefuroxime (parenteral) (parenteral) was also evaluated; however, no change in breakpoints was necessary with the dosage. When using the current breakpoints, routine ESBL testing is no longer necessary before reporting results (ie, it is no longer necessary to edit results for cephalosporins, aztreonam, or penicillins to resistant). However, ESBL testing may still be useful for epidemiological or infection control purposes. For laboratories that have not implemented the current breakpoints, ESBL testing should be performed as described in this table.

b.

Screening of P. of P. mirabilis for mirabilis for ESBL production is recommended only when it is deemed clinically relevant (eg, a bacteremic isolate).

c.

Preparation of ceftazidime-clavulanate ceftazidime-clavulanate (30 g/10 g) and cefotaxime-clavulanate (30 g/10 g) disks: Using a stock solution of clavulanate at 1000 g/mL (either freshly prepared or taken from small aliquots that have been frozen at −70°C), add 10 L of clavulanate to ceftazidime (30 g) and cefotaxime (30 g) disks. Use a micropipette to apply the 10 L of stock solution to the ceftazidime and cefotaxime disks within one hour before they are applied to the plates, allowing about 30 minutes for the clavulanate to absorb and the disks to be dry enough for application. Use disks immediately after preparation or discard; do not store.

d.


Reference for Table 7A 1

CLSI. Performance CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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VET08, 4th ed.

s L B S E r o f s t s e B T 7 n e i o l b t a u T l i d o r c i M h t o r B

Table 7B. Broth Microdilution Tests for Extended-Spectrum -Lactamases in Klebsiella pneumoniae, Klebsiella Klebsiella oxytoca, Escherichia oxytoca, Escherichia coli, and Proteus and Proteus mirabilis Test Medium Antimicrobial concentration

Criteria for Performance of ESBL Test a CAMHB

For K. For K. pneumoniae, K. oxytoca, oxytoca, and E. and E. coli: coli: Cefpodoxime 4 g/mL or Ceftazidime 1 g/mL or Aztreonam 1 g/mL or Cefotaxime 1 g/mL or Ceftriaxone 1 g/mL

For P. For P. mirabilis b: Cefpodoxime 1 g/mL or Ceftazidime 1 g/mL or Cefotaxime 1 g/mL

ESBL Testa

CAMHB Ceftazidime Ceftazidime-clavulanate

0.25 – 128 128 g/mL 0.25/4 – 128/4 128/4 g/mL

and Cefotaxime Cefotaxime-clavulanate

0.25 – 64 64 g/mL – 0.25/4 64/4 64/4 g/mL

(Testing necessitates using both cefotaxime and ceftazidime, alone and in combination with clavulanate.)

Inoculum

(Testing more than on e antimicrobial agent improves the sensitivity of ESBL detection.) Standard broth dilution procedure

Standard broth dilution procedure

Incubation conditions



Incubation length

16–20 hours

16–20 hours

Results

Growth at or above the concentrations listed may indicate ESBL production (ie, for E. for E. coli, K. pneumoniae, pneumoniae, and K. and K. oxytoca, MIC  8 g/mL for cefpodoxime or MIC ≥ 2 µg/mL for ceftazidime, aztreonam, aztreonam, cefotaxime, or ceftriaxone; and for P. for P. mirabilis MIC mirabilis MIC  2 g/mL for cefpodoxime, ceftazidime, or cefotaxime).

A  3 twofold concentration decrease in an MIC for either antimicrobial agent tested in combination with clavulanate vs the MIC of the agent when tested alone = ESBL (eg, ceftazidime MIC = 8 g/mL; ceftazidime-clavulanate MIC = 1 g/mL).

QC recommendations recommendations

When testing antimicrobial agents used for ESBL detection, K. detection, K. pneumoniae ATCC pneumoniae ATCCc 700603 is provided as a supplemental QC strain (eg, for training, competenc e assessment, or test evaluation). Either strain, K. strain, K. pneumoniae ATCC pneumoniae ATCC 700603 or E. coli ATCC coli ATCC 25922, may then be used for routine QC (eg, weekly or daily). E. coli ATCC coli ATCC® 25922 = No growth (see acceptable QC ranges in Table 5A). K. pneumoniae ATCC pneumoniae ATCC® 700603 = Growth: Cefpodoxime Ceftazidime Aztreonam Cefotaxime Ceftriaxone

 8 g/mL  2 g/mL  2 g/mL  2 g/mL  2 g/mL

For all confirmed ESBL-producing strains, see reporting recommendations recommendations in CLSI document M100, 1 Table 3A.

When performing the ESBL test, K. pneumoniae ATCC pneumoniae ATCC 700603 and E. and E. coli  ATCC 25922 should be tested routinely (eg, weekly or daily). Acceptable QC:

E. coli ATCC® 25922: < 3 twofold concentration decrease in MIC for antimicrobial agent tested in combination with clavulanate vs the MIC of the agent when tested alone. K. pneumoniae ATCC pneumoniae ATCC® 700603:  3 twofold concentration decrease in an MIC for an antimicrobial agent tested in combination with clavulanate vs the MIC of the agent when tested alone.

Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton broth; ESBL, extendedspectrum -lactamase; MIC, minimal inhibitory concentration; QC, quality control.

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Table 7B. (Continued) Footnotes a.

Following evaluation evaluation of pharmacokinetic-pharmacodyna pharmacokinetic-pharmacodynamic mic properties, limited clinical data, and MIC distributions for human antimicrobial susceptibility testing data by the Subcommittee on Antimicrobial Susceptibility Testing, revised breakpoints for cefazolin, cefotaxime, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, and aztreonam were published in January 2010 and are listed in CLSI document M100, 1 Table 2A. Cefuroxime (parenteral) was also evaluated; however, no change in breakpoints was necessary with the dosage. When using the current breakpoints, routine ESBL testing is no longer necessary before reporting results (ie, it is no longer necessary to edit results for cephalosporins, aztreonam, aztreonam, or penicillins to resistant). However, ESBL testing may still be useful f or epidemiological epidemiological or infection control purposes. For laboratories that have not implemented the current breakpoints, ESBL testing should be performed as described in this table.

b.

Screening of P. of P. mirabilis for mirabilis for ESBL production is recommended only when it is deemed clinically relevant (eg, a bacteremic isolate).

c.


Reference for Table 7B 1


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C L S I V E T 0 1 S G n e o n i e t r c . i c u p A d d p o m r s i P s n u V e C E c s c T 7 a o 0 e c 1 l m o l S b a y t 3 a c F T h N a p L a - t G β e S r n n e o i f r i c t A s d e m T i n V E T 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With VET01

VET08, 4th ed.

Table 7C. Test for Detection of β-Lactamase Production in Staphylococcus in Staphylococcus spp . Test Test method Organism group

β-Lactamase Productiona Disk Diffusion (penicillin zone-edge test) S. aureus with aureus with penicillin MICs ≤ 0.12 g/mL or zones ≥ 29 mm b

Medium Antimicrobial concentration Inoculum

MHA 10 units penicillin disk Standard disk diffusion procedure

Incubation conditions Incubation length

35°C ± 2°C; ambient air 16–18 hours

Results

Sharp zone edge (“cliff”) = -lactamase positive (see Figure 1 below this table)

Nitrocefin-based test S. aureus and CoNS (including S. (including S. lugdunensisc) with penicillin MICs ≤ 0.12 g/mL or zones ≥ 29 mm N/A N/A b

Induced growth (ie, growth taken from the zone margin surrounding a penicillin or cefoxitin disk test on either MHA or a blood agar plate after 16–18 hours of incubation) Room temperature Up to 1 hour for nitrocefin-based test or follow manufacturer’s directions Nitrocefin-based test: test: conversion from yellow to red/pink = β-lactamase positive.

Fuzzy zone edge (“beach”) = -lactamase negative (see Figure 2 below this table) Additional testing and reporting

β-lactamase-positive staphylococci are resistant to penicillin, amino-, carboxy-, and ureidopenicillins.

Nitrocefin-based tests can be used for S. for S. aureus, but aureus, but negative results should be confirmed with the penicillin zone-edge test before reporting penicillin as susceptible.

β-lactamase-positive staphylococci are resistant to penicillin, amino-, carboxy-, and ureidopenicillins. QC recommendations – routined

ATCC®e 25923 for routine QC of disks to include examination of zone-edge test (fuzzy edge = “beach”)

S. aureus

QC recommendations – lot/shipmentf

S. aureus ATCC® 29213

– positive


– negative

(or see local regulations and manufacturers’ recommendations) QC recommendations – supplementalg


– positive pencillin zone-edge test (sharp edge = “cliff”)

Abbreviations: ATCC®, American Type Culture Collection; CoNS, coagulase-negative staphylococci; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration ; QC, quality control. Footnotes

a.

Refer to VET01,1 Subchapter 7.2.1 for description of methods, testing issues, and reporting recommendations.

b.

The penicillin disk diffusion zone-edge test was shown to be more sensitive than nitrocefin-based tests for detection of βlactamase production in S. aureus. The penicillin zone-edge test is recommended if only one test is used for β-lactamase detection. However, some laboratories may choose to perform a nitrocefin-based test first and, if this test is positive, report the results as positive for β-lactamase (or penicillin resistant). If the nitrocefin test is negative, the penicillin zone-edge test should be performed before reporting the isolate as penicillin susceptible in cases where penicillin may be used for therapy (eg, endocarditis).2,3

c.

For S. For S. lugdunensis, tests for -lactamase detection are not necessary because isolates producing a -lactamase will test penicillin resistant (MIC > 0.12 g/mL and zone diameters < 29 mm). If a laboratory laboratory is using a method other than the CLSI disk diffusion or MIC reference methods and is unsure if the method can reliably detect penicillin resistance with contemporary isolates of S. lugdunensis, the laboratory should perform an induced nitrocefin assay or other CLSI reference method on isolates that test penicillin susceptible before reporting the isolate as penicillin susceptible.

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Table 7C. (Continued) d.

QC recommendations – routine Test negative (susceptible) QC strain: 





With each new lot/shipment of testing materials (eg, disks, or agar plates used for agar dilution, or single wells or tubes used with broth dilution methods) Weekly if the test is performed at least once a week and criteria for converting from daily to weekly QC testing have been met (see Subchapter 8.7.2.3 in VET011) Daily if the test is performed less than once per week and/or if criteria for converting from daily to weekly QC testing have not been met

e.


f.

QC recommendations – lot/shipment Test positive (resistant) QC strain at minimum once with each new lot/shipment of testing materials (eg, disks, or agar plates used for agar dilution, or single wells or tubes used with broth dilution methods).

g.

QC recommendations – supplemental: 



Supplemental QC strains can be used to assess a new test, for training personnel, and for competence assessment. It is not necessary to include supplemental QC strains in routine daily or weekly antimicrobial susceptibility testing QC programs (see Appendix C, which which describes use of QC strains). strains).

NOTE: Information in boldface type is new or modified since the previous edition.

Figure 1. Positive Penicillin Disk Zone-Edge Test for β-Lactamase Detection. The zone edge is sharp or like a “cliff” indicating β-lactamase production.

Figure 2. Negative Penicillin Disk Zone-Edge Test for β-Lactamase Detection. The zone edge is fuzzy or like a “beach” indicating no β-lactamase production.

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n o i t c . u d p p o r s P s u c C e c 7 s a o c e l m o b t a l y a c h T a p L a - t β S r n o i f t s e T

C L S I V E T 0 1 S G n e o n i e t r c . i c u p A d d p o m r s i P s n u V e C E c s c T 7 a o 0 e c 1 l m o l S b a y t 3 a c F T h N a p L a - t G β e S r n n e o i f r i c t A s d e m T i n V E T 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With VET01

VET08, 4th ed.

Table 7C. (Continued) References for Table 7C 1

CLSI. Performance CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests Tests for Bacteria Isolated From Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

2

Kaase M, Lenga S, Friedrich S, et al. Comparison of phenotypic methods for penicillinase detection in Staphylococcus aureus. aureus. Clin Microbiol Infect. 2008;14(6):614-616. Infect. 2008;14(6):614-616.

3

Gill VJ, Manning CB, Ingalls CM. Correlation of penicillin minimum inhibitory concentrations and penicillin zone edge appearance with staphylococcal beta-lactamase production. J production. J Clin Microbiol. Microbiol. 1981;14(4):437-440.

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C L S I V E s T 0 - u e 1 r A S c u e a G s m e u f n e o c c r i n o c c A o i o d l t m c y i i n d h p V e E D r a T 7 P t 0 e r S 1 l o n S b f i 3 a e t F T s c N e n T a G t n e s i n o i s e s e r i u R c A ff i d d e m D t i n a k V s i i d E D e T 0 M 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With VET01

VET08, 4th ed.

Table 7D. Disk Diffusion Testa for Prediction of mecA mecA-Mediated -Mediated Resistance in Staphylococcib Antimicrobial Agent Cefoxitin

Disk Content 30 g

Organism Group Staphylococcus aureus and Staphylococcus lugdunensis

CoNS

Oxacillin

1 µg µg

Staphylococcus pseudintermedius and Staphylococcus schleiferi

Zone Diameter Breakpoints, nearest whole mm  21  22

 24

 25

 17

 18

Comments S. aureus for aureus for which cefoxitin disk diffusion zones are  21 mm should be reported as oxacillin oxacillin resistant. resistant. Those for which cefoxitin zones are  22 mm should be reported as oxacillin oxacillin susceptib susceptible. le. CoNS for which cefoxitin disk diffusion zones are  24 mm should be reported as oxacillin oxacillin resistant. resistant. Those for which cefoxitin zones are  25 mm should be reported as oxacillin oxacillin susceptib susceptible. le. Oxacillin disk test best detects mecA-mediated mecA-mediated resistance in S. pseudintermedius. Cefoxitin breakpoints are not predictive of mecA-mediated mecA-mediated resistance in S. pseudintermedius.

Abbreviation: CoNS, coagulase-negative staphylococci. Footnotes

a.

Use standard disk diffusion testing conditions and incubate for 18 hours for S. aureus and aureus and 24 hours for CoNS. Results may be reported for CoNS after 18 hours of incubation if resistant. Read the cefoxitin disk test using reflected light.

b.

Refer to VET01,1 Subchapter 7.2.2 for description of methods, testing issues, and reporting recommendations.

NOTE: Information in boldface type is new or modified since the previous edition. Reference for Table 7D 1

130

CLSI. Performance CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Bacteria Isolated From Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

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For Use With VET01

VET08, 4th ed.


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131

C L S I V E T s 0 1 u c S c o G c e o . l n y p e h p r i c p s A a s d t m S u c r c i n o o V c f E E o T 7 n r 0 e e e t 1 l e S b r n 3 a c E S d F T N r n a a G g s e A n u e n e i r i c r c A y u a d m m o i n c V n E a T V 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With VET01

VET08, 4th ed.

Table 7E. Vancomycin Agar Screen for Staphylococcus for Staphylococcus aureus and Enterococcus and Enterococcus spp. Screen Test Screen Test Organism group Medium Antimicrobial concentration Inoculum

Incubation conditions Incubation length Results

Additional testing and reporting

Vancomyc Vancomycin in MIC ≥ 8 g/mL Enterococcus spp. BHI a agar

Staphylococcus au aureus BHI agar 6 g/mL vancomycin

6 g/mL vancomycin

Colony suspension to obtain 0.5 McFarland turbidity

1–10 L of a 0.5 McFarland suspension spotted onto agar surface

Preferably, using a micropipette, spot a 10-L drop onto agar surface. Alternatively, using a swab dipped in the suspension and the excess liquid expressed, spot an area 10–15 mm in diameter or streak a portion of the plate. 35° ± 2°C; ambient air 24 hours Examine carefully with transmitted light for  1 colony or light film of growth.

Alternatively, using a swab dipped in the suspension and the excess liquid expressed, spot an area 10–15 mm in diameter or streak a portion of the plate.

 1 colony = Presumptive reduced susceptibility to vancomycin Perform a vancomycin MIC using a validated MIC method to determine vancomycin MICs on S. on S. aureus that aureus that grow on BHI-vancomycin screening agar. Testing on BHI-vancomycin screening agar does not reliably detect all vancomycin-intermediate S. vancomycin-intermediate S. aureus strains. Some strains for which the vancomycin MICs are 4 g/mL will fail to grow.

QC recommendations – routineb QC recommendations – lot/shipmentd

Enterococcus faecalis faecalis ATCCc 29212 – susceptible E. faecalis ATCC 51299 – resistant

35°C ± 2°C; ambient air 24 hours > 1 colony = Presumptive vancomycin resistance

Perform vancomycin MIC on Enterococcus spp. Enterococcus spp. that grow on BHIvancomycin screening agar and test for motility and pigment production to distinguish species with acquired resistance (eg, vanA and vanA and vanB) vanB) from those with intrinsic, intermediate-level resistance to vancomycin (eg, vanC ), ), such as Enterococcus as Enterococcus gallinarum, gallinarum, Enterococcus casseliflavus, casseliflavus, or or Enterococcus flavescens flavescens,, which often grow on the vancomycin screen plate. In contrast to other enterococci, E. enterococci, E. gallinarum, E. casseliflavus, casseliflavus, and E. and E. flavescens with vancomycin MICs of 8–16 g/mL (intermediate) differ from vancomycin-resistant enterococci for infection control purposes. E. faecalis ATCC 29212 – susceptible E. faecalis ATCC 51299 – resistant

Abbreviations: ATCC®, American Type Culture Collection; BHI, brain heart infusion; MIC, minimal inhibitory concentration; QC, quality control. Footnotes

a.

BHI: Even though not as widely available, dextrose phosphate agar and broth have been shown in limited testing to perform comparably.

b.

QC recommendations – routine Test negative (susceptible) QC strain: 

132

With each new lot/shipment of testing materials

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For Use With VET01

VET08, 4th ed.

Table 7E. (Continued) 



Weekly if the test is performed at least once per week and criteria for converting from daily to weekly QC testing have been met (see Subchapter Subchapter 8.7.2.3 in VET011) Daily if the test if the test is performed less than once per week and/or if criteria for converting from daily to weekly QC testing have not been met

c.


d.

QC recommendations – lot/shipment Test positive (resistant) QC strain at minimum with each new lot/shipment of testing materials

Reference for Table 7E 1

©



133

s u c c o c o . l y p h p p s a s t S u c r c o o E f c 7 n o r e e e t l e n b r c E a S

T d r n a a g A s u n e i c r y u a m o c n a V

C L S I V E T 0 e 1 a S i , . n p o G p e s m n s u e u e r c i c c n A p o d c s m o u l i n y c c V h o E p c T o a 0 t t 1 p S S e 3 r n i t F S N e c d G n n e a a n t e F s , i r i 7 s p c e e u A l d b R o m a r G n i i n T c c i V y t E y T m l 0 a o 1 d m S n 3 i l e L N C H e β l . 0 b 8 p i / c p 1 u s 6 / d s 2 n u 0 I c 1 r c 8

o o c f o t s t e p T e r

t S

For Use With VET01

VET08, 4th ed.

Table 7F. Test for Detection of Inducible Clindamycin Resistance in Staphylococcus in Staphylococcus spp., Streptococcus spp., Streptococcus spp. spp. -Hemolytic Group, and Streptococcus and Streptococcus pneumoniae Test Test method Organism groupa

Medium

Antimicrobial concentration Inoculum

Inducible Clindamycin Resistance Disk Diffusion (D-zone test) Broth Microdilution Staphylococcus aureus, S. aureus, S. Streptococcus spp. -hemolytic Staphylococcus lugdunensis, lugdunensis, and hemolytic group b and Streptococcus spp. lugdunensis, lugdunensis, and CoNS CoNS Streptococcus -hemolytic group b pneumoniae and S. pneumoniae MHA or blood agar MHA supplemented CAMHB CAMHB with LHB purity plate used with with sheep blood (5% (2.5% to 5% v/v) MIC tests v/v) or TSA supplemented with sheep blood (5% v/v) 15-µg erythromycin and 15-µg erythromycin 4 µg/mL 1 µg/mL 2-µg clindamycin disks and 2-µg clindamycin erythromycin and 0.5 erythromycin and 0.5 spaced 15–26 mm apart disks spaced 12 mm µg/mL clindamycin µg/mL clindamycin apart in same well in same well Standard disk diffusion Standard disk diffusion Standard broth microdilution procedure procedure procedure

or heavily inoculated area of purity plate Incubation conditions


35°C ± 2°C; 5% CO2


Incubation length

16–18 hours

20–24 hours

18–24 hours

Results

Flattening of the zone of inhibition adjacent to the erythromycin disk (referred to as a D-zone)= D-zone) = inducible clindamycin resistance.

Additional testing and reporting

QC recommendations – routinec

QC recommendations – lot/shipment lot/shipmente QC recommendations – supplemental supplementalf

20–24 hours

Any growth = inducible clindamycin resistance

No growth = no inducible clindamycin Hazy growth within the zone of inhibition around resistance. clindamycin = clindamycin resistance, even if no Dzone is apparent. Report isolates with inducible clindamycin resistance as “resistant to clindamycin, clindamycin, lincomycin, and pirlimycin.” The following comment may be included with the report: “This isolate is presumed to be resistant to lincosamides lincosamides (clindamycin, lincomycin, pirlimycin) based on detection of inducible clindamycin resistance.” S. aureus ATCC® 25923 S. pneumoniae ATCC pneumoniae ATCC® S. aureus ATCC aureus ATCC® S. pneumoniae for routine for routine QC of 49619 for routine QC BAA-976™d or S. S. ATCC® 49619 or S. erythromycin and of erythromycin and aureus ATCC aureus ATCC® aureus ATCC aureus ATCC® clindamycin disks clindamycin disks 29213 – no growth BAA-976™ – no growth S. aureus ATCC aureus ATCC® BAA-977™ – growth

S. aureus ATCC aureus ATCC® BAA-976™ (D-zone test negative)

S. aureus ATCC aureus ATCC® BAA-976 ™ (no growth) S. aureus ATCC aureus ATCC® BAA-977 ™ (growth)

S. aureus ATCC aureus ATCC® BAA-977™ (D-zone test positive) Use of unsupplemented MHA is acceptable for these strains. Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton broth; CoNS, coagulasenegative staphylococci; LHB, lysed horse blood; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; QC, quality control; TSA, tryptic soy agar.

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For Use With VET01

VET08, 4th ed.

e

a , . i p n o p s m

Table 7F. (Continued) Footnotes

a.

Applies only to organisms resistant to to erythromycin and susceptible susceptible or intermediate to lincosamides lincosamides (clindamycin, (clindamycin, lincomycin, lincomycin, pirlimycin).

b.

Antimicrobial susceptibility testing (AST) of -hemolytic streptococci does not need to be performed routinely (see CLSI document M100,1 Table 2H-1). When AST is clinically indicated, it should include testing for inducible lincosamide resistance.

c.

QC recommendations – routine Test negative (susceptible) QC strain:

d.



With each new lot/shipment of testing materials (eg, disks, or agar plates used for agar dilution, or single wells or tubes used with broth dilution methods)



Weekly if the test is performed at least once a week and criteria for converting from daily to weekly QC testing have been met (see Subchapter Subchapter 8.7.2.3 in VET012)



Daily if the test is performed less than once per week and/or if criteria for converting from daily to weekly QC testing have not been met

ATCC® is a registered trademark of the American Type Culture Collection. Per ATCC® convention, the trademark

symbol is used after “BAA” in each catalog number, in conjunction with the registered ATCC® name. e.

QC recommendations – lot/shipment

QC recommendations – supplemental



Supplemental QC strains can be used to assess a new test, for training personnel, and for competence assessment



It is not necessary to include supplemental QC strains in routine daily or weekly AST QC programs (see Appendix C, which describes use of QC strains)

References for Table 7F 1


2

CLSI. Performance CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Bacteria Isolated From Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

©


e c d n n a t F s a , i 7 s p u e e l r b R o a n G T i c c i y t y m l a o d m n i l e H C e β l . b p i c p u s d s n u I c r c o c f o o t s t e p T e r

t S

Test positive (resistant) QC strain at minimum once with each new lot/shipment of testing materials (eg, disks, or agar plates used for agar dilution, or single wells or tubes used with broth dilution methods) f.

s u u e c c n p o c s o u l y c c h o p c o a t t S p e r n i t S

135


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Table 7G. (Continued) Test Gentamicina HLAR Streptomycina HLAR Enterococcus faecalis faecalis E. faecalis ATCC® E. faecalis ATCC® E. aecalis ATCC aecalis ATCC® E. faecalis ATCC® E. faecalis ATCC® QC 29212 – Susceptible 29212 – Susceptible 29212: 29212 – Susceptible 29212 – Susceptible recommendations ATCC®d 29212: 16– 23 mm 14–20 mm – routinec E. faecalis ATCC® E. faecalis ATCC® E. faecalis ATCC® E. faecalis ATCC® QC 51299 – Resistant 51299 – Resistant 51299 – Resistant 51299 – Resistant recommendations – lot/shipment lot/shipment e Abbreviations: ATCC®, American Type Culture Collection; BHI, brain heart infusion; CSF, cerebrospinal fluid; HLAR, high-level aminoglycoside resistance; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; QC, quality control.


Footnotes

a.

Synergy between ampicillin, penicillin, penicillin, or vancomycin and an aminoglycoside can be predicted for enterococci by using a high-level aminoglycoside (gentamicin and streptomycin) screening test. Other aminoglycosides do not need to be tested, because their activities against enterococci are not superior to gentamicin and streptomycin.

b.

BHI: Even though they are not as widely available, dextrose phosphate agar and broth have been shown in limited testing to perform comparably.

c.

QC recommendations – routine Test negative (susceptible) QC strain: 

With each new lot/shipment of testing materials



Weekly if the test is perfor med at least once a week and criteria for converting from daily to weekly QC testing have been met (see Subchapters 8.7.2.1–8.7.2.3 in VET01 1)



Daily if the test is performed less than o nce per week and/or if criteria for converting from daily to weekly QC testing have not been met

d.


e.

QC recommendations – lot/shipment Test positive (resistant) QC strain at a minimum with each new lot/shipment of testing materials.

References for Table 7G 1

CLSI. Performance CLSI. Performance Standards for Antimicrobial Antimicrobial Disk and Dilution Dilution Susceptibility Tests for Bacteria Bacteria Isolated From Animals. 5th ed. CLSI standard VET01. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

2

Torres C, Tenorio C. Lantero M, Gastañares MJ, Baquero F. High-level penicillin resistance and penicillin-gentamicin penicillin-gentamicin synergy in Enterococcus faecium. Antimicrob Agents Chemother. 1993;37(11):2427-2431. Chemother. 1993;37(11):2427-2431.

3

Murray BE. Vancomycin-resistant enterococci. Am enterococci. Am J Med. 1997;102(3):284-293. Med. 1997;102(3):284-293.

1 3 7

Table 7G Test for High-Level Aminoglycoside Resistance in Enterococcus Enterococcus spp. spp.

V E T 0 8 , 4 t h e d .


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Appendix A. (Continued)

Organism or Organism Group Enterococcus faecium faecium

Enterococcus faecalis faecalis Staphylococcus aureus Staphylococcus pseudintermedius Staphylococcus, coagulase-positive Staphylococcus pseudintermedius Staphylococcus, coagulase-negative Streptococcus pneumoniae

Streptococcus equi subsp. equi subsp. equi and subsp. zooepidemicus subsp. zooepidemicus Streptococcus, β-hemolytic Streptococcus, β-hemolytic group, including Streptococcus equi subsp. zooepidemicus and equi, and equi, Streptococcus canish Streptococcus, Streptococcus, viridans group Bordetella bronchiseptica bronchiseptica

Resistance Phenotype Detecteda High-level aminoglycoside – R Vancomycin – R Resistant to ampicillin (consider misidentification) Vancomycin MIC ≥ 8 µg/mLf Vancomycin MIC = 4 µg/mL Chlora Chloramph mpheni enicol col – R Oxacillin – R Amikacin – R

Occurrence and Significance of Resistance and Actions to Take Following Confirmation of Results a Category I Category II b Category III b Uncommon and of veterinary importance, May be common, but is not reported or only Uncommon in most generally considered of rarely reported to date institutions epidemiological concern X X


X Xf X X X

Vancomycin – I or R g Chlora Chloramph mpheni enicol col – R Vancomycin – NS

X

Fluoroquinolone – I or R Rifampin – I or R Using nonmeningitis breakpoints: Amoxicillin or penicillin – R Extended-spectrum cephalosporine – R Amikacin – I or R

X

Ampicillin or penicillin – NS Extended-spectrum cephalosporine – NS Vancomycin – NS

X

Vancomycin – NS Chloramphenicol – R Amikacin – I or R Fluoroquinolones – I or R Chlora Chloramph mpheni enicol col – R

X

X

X

X

X

V E T 0 8 , 4 t h e d .

1 3 9

Appendix A Suggested Test Result Confirmation and Organism Identification


©



Appendix B. (Continued) B1. (Continued) Antimicrobial Agent

Organism Serratia marcescens Yersinia enterocolitica Yersinia pseudotuberculosis

, n n i l i l l l i i c c i i p x o m m A A

R R

- e n t i l a l i n c l a i x u o v a m l A c

R R

n m i l a l i t c c i a p b l m u A s

R R

n i l l i c a r e p i P

n i l l i c r a c i T

R

s n , , n i , n l i r i h n i o i x x l e p o t o o l r s : z o I a a d l a l h a h a f p f e e p h e e p C C C e C C

: s , n n i i n c t a y i t e t m x o o a f f h e e p C C e C

s , n i e e r m m o i m e p : x i x n s o e o I o l I r r i u p a u f h f m e e p I e C C C

R R

R R

R

s e n i l c y c a r t e T

n i o t n a r u f o r t i N

R

n i t s i l o C

R

R

Abbreviation: R, resistant.

Warning: For Salmonella spp. Salmonella spp. and Shigella spp., Shigella spp., aminoglycosides, first- and second-generation cephalosporins, and cephamycins may appear active in vitro but vitro but are not effective clinically and should not be reported as susceptible. Footnotes

a.

E. cloacae complex cloacae complex includes Enterobacter asburiae, Enterobacter cloacae, and cloacae, and Enterobacter Enterobacter hormaechei. hormaechei. Other members of the complex include Enterobacter kobei and kobei and Enterobacter ludwigii, for ludwigii, for which antimicrobial susceptibility susceptibility testing data are not available.

b.

Proteus spp. Proteus spp. and Morganella and Morganella spp. spp. may have elevated minimal inhibitory concentrations to imipenem by mechanisms other than by production of carbapenemases. Isolates that test as susceptible should be reported as susceptible.

NOTE 1: Cephalosporins III, cefepime, aztreonam, aztreonam, ticarcillin-clavulanate, ticarcillin-clavulanate, piperacillin-tazobactam, piperacillin-tazobactam, and the carbapenems are not listed, because there is no intrinsic resistance in Enterobacteriace in Enterobacteriaceae. ae. NOTE 2: Enterobacteriaceae are also intrinsically resistant to clindamycin, fusidic acid, glycopeptides (vancomycin), macrolides (erythromycin, clarithromycin, clarithromycin, and azithromycin), and rifampin. However, there are some exceptions with macrolides (eg, Salmonella and Shigella spp. Shigella spp. with azithromycin).

V E T 0 8 , 4 t h e d .

1 4 3

Appendix B Intrinsic Resistance


Appendix B Intrinsic Resistance 1 4 4

Appendix B. (Continued) B2. Non- Enterobacteriaceae Antimicrobial Agent

Organism

Acinetobacter baumannii/ Acinetobacter calcoaceticus complex Achromobacter xylosoxidans xylosoxidans ©


Burkholderia cepacia cepacia complex Pseudomonas aeruginosa aeruginosa

n i l l i c i x o m A , n i l l i c i p m A

m a t c n n a i b i l l l l i u i c l c a r s r n a i e c l l p i i i c P T i p m A a

R

e t a n a l u v a l c n i l l i c i x o m A

m a t c a b o z a t n i l l i c a r e p i P

e e e m n o i m i x x a p t a i e r f o t e f f e e C C C

R

R

R R

R

R

R

R

R

R

R

R

R

n i m c m e a m a e n x n n o o e e l f e p p o r i o t r r z m e p A I i M C

R

R

R

R

R

R

R

R

R

R

R

s m i n e n x y e p m a l y t r o E P

s e d i s o c y l g o n i m A

R

R

R

R

R

m i r p o h t e m i r T

e - l o m z i r a p x o o h h t t e e m m a i r f l T s u

l o c i n e h p m a r o l h C

R

R

R

R

R R

R

R

R

R

R

R

Stenotrophomonas maltophilia R

/ s e e n n i i l l c c y y c c e a g r i t e T T

V E T 0 8 , 4 t h e d .

R

R

R

R

R

R

R

R b

R

R

R

Abbreviation: R, resistant. Footnotes

a.

A. baumannii/calcoaceticus baumannii/calcoaceticus may may appear to be susceptible to ampicillin-sulbactam due to the activity of sulbactam with this species.

b.

S. maltophilia is maltophilia is intrinsically resistant to tetracycline but not to doxycycline, minocycline, or tigecycline.

NOTE: These nonfermentative gram-negative bacteria are also intrinsically resistant to penicillin (ie, b enzylpenicillin), enzylpenicillin), cephalosporins I (cephalothin, cefazolin), cephalosporin II (cefuroxime), cephamycins (cefoxitin, cefotetan), clindamycin, fusidic acid, glycopeptides (eg, vancomycin), macrolides (erythromycin, azithromycin, clarithromycin), and rifampin.



For Use With VET01

VET08, 4th ed.

Appendix B. (Continued) B3. Staphylococci Antimicrobial Agent

Organism Staphylococcus aureus, Staphylococcus lugdunensis Staphylococcus epidermidis

e c n a B t x i i s d s e n e R c p i p s n A i r t n I

d i c A c i d i s u F

n i c o i b o v o N

There is no intrinsic resistance in these species

Staphylococcus haemolyticus Staphylococcus saprophyticus

R

R

Staphylococcus capitis Staphylococcus cohnii

R

Staphylococcus xylosus

R

Abbreviation: R, resistant.

NOTE 1: These gram-positive bacteria are also intrinsically resistant to aztreonam, nalidixic acid, and polymyxins (including colistin). NOTE 2: Oxacillin-resistant S. aureus aureus and coagulase-negative staphylococci (methicillin-resistant staphylococci [MRS]) are considered resistant to other -lactam agents, ie, penicillins, -lactam combination agents, cephems (with the exception of the cephalosporins with anti-MRSA [methicillin-resistant [methicillin-resistant S. aureus] aureus] activity), and carbapenems. This is because most cases of documented MRS infections have responded poorly to -lactam therapy, or because convincing clinical data that document clinical efficacy for those agents have not been presented.

B4. Enterococcus spp. Antimicrobial Agent

Organism Enterococcus faecalis faecalis

Enterococcus faecium faecium Enterococcus gallinarum/Enterococcus gallinarum/Enterococcus casseliflavus

e - l o m z i r a p x o o h h t t e e m m i f a r l T u s


n i c y m a d n i l C


R a

R a

R a

R

R a

R

R a

R a

R a

R

R a

R

R a

R a

R

R a

R

s n i r o p s o l a h p e C

R a

n i c y m o c n a V

R

d i c A c i d i s u F

Abbreviation: R, resistant. Footnote

a.

For Enterococcus spp., spp., cephalosporins, aminoglycosides (except for high-level resistance testing), clindamycin, Warning: For Enterococcus and trimethoprim-sulfamethoxazole may appear active in vitro but vitro but are not effective clinically and should not be reported as susceptible.

NOTE: These gram-positive bacteria are also intrinsically resistant to aztreonam, nalidixic acid, and polymyxins (including colistin).

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145


For Use With VET01

VET08, 4th ed.

Appendix B. (Continued) e c n a B t x i i s d s e n e R c p i p s n A i r t n I

B5. Other Gram-Positive Bacteria of Importance in Veterinary Medicine s n ) i e r o t m p p i s e d o c i l x z a e a h ( t f p e e c C

Antimicrobial Agent n i l l i c i n e P

Organism

Bacillus cereus cereusa

e m i d i z a t f e C

n i c y m o c n a V

R

Corynebacterium spp. Erysipelothrix rhusiopathiae

R

Lactobacillus spp. (some species) R Listeria monocytogenes monocytogenes

R

R


a.

B. cereus may cereus may be resistant to other β-lactam agents due to chromosomally encoded β-lactamases.

NOTE: These gram-positive bacteria are also intrinsically resistant to aztreonam, nalidixic acid, and polymyxins (including colistin).

B6. Other Gram-Negative Bacteria of Importance in Veterinary Medicine Antimicrobial Agent

Organism Arcobacter butzleri, butzleri, Arcobacter cryaerophilus, Arcobacter skirrowii Neisseria spp.

s e n o l o n i u q o r o u l F

n i h t o l a h p e C

s n i m a r g o t p e r t S


d i c A c i x i d i l a N

a

R

a

Campylobacter fetus Campylobacter jejuni subsp. jejuni , , Campylobacter Campylobacter coli

d i c a c i d i s u F

R

R

a

R

R

R

a

R

R

R

R


a.

146

Resistance to fluoroquinolones is frequently mediated by a mutation in the gyrA the gyrA gene, gene, and resistance to macrolide antibiotics is due to ribosomal mutation. Campylobacter jejuni subsp. jejuni subsp. doylei is susceptible to cephalothin.

©



For Use With VET01

VET08, 4th ed.

Appendix B. (Continued) B7. Anaerobic Gram-Positive Bacilli Antimicrobial Agent

Organism Clostridium spp.

Clostridium innocuum

n i c y m o c n a V

e c n a B t x i i s d s e n e R c p i p s n A i r t n I


R R

R


n i l l i c i n e P

n i l l i c i p m A

R

R

R

Abbreviation: Abbreviation: R, resistant.

B8. Anaerobic Gram-Negative Bacilli Antimicrobial Agent

Organism

Bacteroides spp. Fusobacterium canifelinum canifelinum

R

s e n o l o n i u Q

R

Abbreviation: Abbreviation: R, resistant.

©


147


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Appendix C. (Continued) QC Strains E. coli ATCC® 35218d,e,2,3

Organism Ch Characteristics  Contains plasmidencoded TEM-1 -lactamase (non-ESBL)  Contains SHV-18 ESBL2,3

Disk Di Diffusion Te Tests  -lactam combination agents  ESBL tests  -lactam combination agents

MIC Te Tests  -lactam combination agents  ESBL tests  -lactam combination agents

Pseudomonas aeruginosa ATCC® 27853f

 Contains inducible AmpC β-lactamase

 Nonfastidious gram-negative bacteria

 Nonfastidious gram-negative bacteria

Staphylococcus aureus ATCC® 25923

 -lactamase negative  mecA negative mecA negative

 Nonfastidious gram-positive bacteria


 Weak -lactamase– producing strain  mecA negative mecA negative


 Oxacillin-resistant, mecA positive mecA positive

S. aureus ATCC® BAA-976™

 msrA-mediated msrA-mediated macrolide-only resistance

S. aureus ATCC® BAA-977™

 Inducible ermAermAmediated resistance

Klebsiella pneumoniae ATCC® 700603e

 Cefoxitin MIC testing

Comments

 Assess suitability of cation content in each batch/lot of CAMHB. CAMHB.  Inducible clindamycin resistance disk diffusion (D-zone) test

 Nonfastidious gram-positive bacteria  Cefoxitin disk diffusion testing

Other Tests


 Little value in MIC testing due to its extreme susceptibility to most drugs drugs

 Oxacillin salt agar  Inducible clindamycin resistance MIC test  Penicillin zone-edge test  Oxacillin salt agar  Inducible clindamycin resistance MIC test and disk approximation test (D-zone test)  Inducible clindamycin resistance MIC test and disk approximation test (D-zone test)

V E T 0 8 , 4 t h e d .

1 4 9

Appendix C QC Strains


©


Appendix C. (Continued) References for Appendix C 1


2

Rasheed JK, Anderson GJ, Yigit H, et al. Characterization of the extended-spectrum beta-lactamase reference strain, Klebsiella pneumoniae K6 pneumoniae K6 (ATCC® 700603), which produces the novel enzyme SHV-18. Antimicrob SHV-18. Antimicrob Agents Chemother. Chemother. 2000;44(9):2382-2388.

3

Queenan AM, Foleno B, Gownley C, Wira E, Bush K. Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and coli and Klebsiella Klebsiella pneumoniae clinical pneumoniae clinical isolates tested by using NCCLS ESBL methodology. J methodology. J Clin Microbiol. 2004;42(1):269-275.


V E T 0 8 , 4 t h e d .

1 5 1

Appendix C QC Strains


For Use With VET01

VET08, 4th ed.

s e u l a V ff o D t u x i C d l n a c e i p g p o l A o i m e d i p E

Appendix D. Epidemiological Cutoff Values Abbreviations for Appendix D

ECV MIC NWT WT

epidemiological cutoff value minimal inhibitory concentration non-wild-type wild-type

D1

Defining Epidemiological Cutoff Values

D1.1

Definitions

epidemiological cutoff value (ECV) – the minimal inhibitory concentration (MIC) or zone diameter value that separates microbial populations into those with and without acquired and/or mutational resistance based on their phenotypes (wild-type [WT] or non-wild-type [NWT]). The ECV defines the highest MIC or smallest zone diameter for the WT population of isolates. EXAMPLE: Interpretive Category Wild-type Non-wild-type 



D1.2

ECVs Zone Diameter, mm ≥ 20 ≤ 19

MIC, μg/mL ≤4 ≥8

wild-type (WT) – an an ECV interpretive category defined by an ECV that describes isolates with no phenotypically detectable mechanisms of acquired resistance or reduced susceptibility susceptibility for the antimicrobial agent being evaluated. non-wild-type (NWT) – an an ECV interpretive category defined by an ECV that describes isolates with presumed or known mechanisms of acquired resistance and reduced susceptibility for the antimicrobial agent being evaluated. Epidemiological Cutoff Values vs Clinical Breakpoints

ECVs are based on in vitro data only, using MIC or zone diameter distributions. ECVs are not clinical breakpoints, and the clinical relevance of ECVs for a particular patient has not yet been identified or approved by CLSI or any regulatory agency. ECVs are principally used to signal the emergence of NWT strains. For more information on ECVs, refer to CLSI document VET05. 1 By contrast, clinical breakpoints are established using MIC distributions, pharmacokinetic pharmacodynamic data, and clinical outcome data, when available (as described described in CLSI document document VET02 VET02 2 or CLSI document M23 3 for human medical breakpoints). “Caution”: Zone diameter (disk diffusion) and MIC values for which ECVs are defined are not to be interpreted or reported as susceptible, intermediate, or resistant, but rather as WT or NWT. The ECVs should not be used as clinical breakpoints.

152

©



For Use With VET01

VET08, 4th ed.

Appendix D. (Continued) Additional information about establishing ECVs and their use by the medical microbiology laboratory is in CLSI document M100. 4 References for Appendix D 1

CLSI. Generation, Presentation, and Application of Antimicrobial Susceptibility Test Data for Bacteria of Animal Origin; A Report . CLSI document VET05-R. Wayne, PA: Clinical and Laboratory Standards Institute; 2011.

2

CLSI. Development CLSI. Development of In Vitro Susceptibility Vitro Susceptibility Testing Criteria and Quality Control Parameters for Veterinary Antimicrobial Agents; Approved Guideline—Third Edition. Edition. CLSI document VET02-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.

3

CLSI. Development CLSI. Development of In Vitro Susceptibility Vitro Susceptibility Testing Criteria and Quality Control Parameters. Parameters. 5th ed. CLSI guideline M23. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

4


©


153

s e u l a V ff o D t u x i C d l n a c e i p g p o l A o i m e d i p E

C L S I V E T 9 0 / 1 s 9 S 9 n 1 o G i e t e i c n d n e d i r S i A s c A t t d n n m i e i n E o p m V e x k l E i T d a p e 0 1 n r p B u S e 3 p c S F p fi 1 i N A c 0 T G e E e p V n S - o e y r i r t c A a s d n n i m o r i i e i n s t V e v E V e T R 0 1 S 3 L N 0 8 / 1 6 / 2 0 1 8

For Use With VET01

VET08, 4th ed.

Appendix E. CLSI Veterinary-Specific Breakpoint Additions/Revisions to VET01 Supplements*† Since 1999 Antimicrobial Agent

Organism(s)

Animal Species

Body Site

Supplement Edition (Date of Addition/Revision)*

Enterobacteriaceae Enterobacteriaceae (38)

Amikacin

Escherichia coli coli

Dogs

VET01S, 3rd ed. (2015)

Amikacin

E. coli

VET01S, 3rd ed. (2015)

Amikacin

E. coli

Ampicillin

E. coli

Horses (adults) Horses (foals) Dogs

SST, UTI

VET01-A3 (2008)

Ampicillin Ampicillin Amoxicillinclavulanate Amoxicillinclavulanate

E. coli E. coli E. coli

Cats Cattle Dogs

SST, UTI Metritis SST

E. coli

Dogs

UTI

VET08 (2018) VET08 (2018) VET01-S2 (2013) M31-A (1999) VET01S, 3rd ed. (2015) M31-A (1999)


E. coli

Cats

SST, UTI

VET01-S2 (2013)

Cefazolin Cefazolin

E. coli E. coli Klebsiella pneumoniae Proteus mirabilis mirabilis E. coli

Dogs Dogs

SST UTI

VET01-S2 (2013) VET08 (2018)

Horses

Gen, Resp

VET01-S2 (2013)

E. coli P. mirabilis mirabilis E. coli E. coli K. pneumoniae P. mirabilis mirabilis E. coli K. pneumoniae P. mirabilis mirabilis E. coli

Dogs

UTI

VET08 (2018)

Cats Dogs

UTI UTI

VET08 (2018) VET08 (2018)

Dogs

Wds/Absc

VET01-A3 (2008)

Cattle

Mastitis

VET01-A3 (2008)

Swine

Resp

M31-A (1999)

Dogs

SST

VET08 (2018)

Dogs

UTI

VET08 (2018)

Cephalothin

E. coli K. pneumoniae P. mirabilis mirabilis E. coli

Dogs

SST

VET01-S2 (2013)

Difloxacin

Enterobacteriaceae

Dogs

SST, UTI

M31-A2 (2002)

Doxycycline

E. coli

Horses

Resp, SST

VET08 (2018)

Enrofloxacin

Enterobacteriaceae

Dogs

Resp, SST, UTI

M31-A (1999)

Enrofloxacin

Enterobacteriaceae

Cats

SST

M31-A (1999)

Enrofloxacin

E. coli

Horses

Resp, SST

VET08 (2018)

Cefazolin Cefovecin Cefovecin Cefpodoxime

Cefpodoxime

Ceftiofur Ceftiofur

Cephalexin Cephalexin

154

Salmonella enterica subsp. enterica subsp. enterica serovar Choleraesuis E. coli

©

VET01S, 3rd ed. (2015)



For Use With VET01

VET08, 4th ed.

Appendix E. (Continued) Antimicrobial Agent Organism(s) Enterobacteriaceae (Continued) Enrofloxacin E. coli

Poultry

Florfenicol

Swine

S. enterica subsp. enterica serovar Choleraesuis Enterobacteriaceae Enterobacteriaceae Enterobacteriaceae Enterobacteriaceae E. coli Enterobacteriaceae Enterobacteriaceae Enterobacteriaceae

Gentamicin Gentamicin Marbofloxacin Marbofloxacin Minocycline Orbifloxacin Orbifloxacin Piperacillintazobactam Pradofloxacin E. coli Pradofloxacin E. coli Pseudomonas aeruginosa (8) Amikacin P. aeruginosa Amikacin P. aeruginosa Amikacin P. aeruginosa Enrofloxacin P. aeruginosa Enrofloxacin P. aeruginosa Gentamicin P. aeruginosa Gentamicin P. aeruginosa Piperacillin P. aeruginosa tazobactam Staphylococcus spp. (34) Amikacin Staphylococcus spp. Amikacin Staphylococcus aureus Amikacin S. aureus Ampicillin Staphylococcus pseudintermedius Ampicillin Staphylococcus spp. AmoxicillinStaphylococcus spp. clavulanate AmoxicillinStaphylococcus spp. clavulanate AmoxicillinStaphylococcus spp. clavulanate Cefazolin S. aureus S. pseudintermedius Cefovecin S. pseudintermedius S. pseudintermedius Cefpodoxime S. aureus S. pseudintermedius Ceftiofur S. aureus Cephalexin S. aureus S. pseudintermedius Cephalothin S. aureus S. pseudintermedius

©

Animal Species

Body Site

Supplement Edition/Date of Addition/Revision*

M31-A (1999) Resp

M31-S1 (2004)

Dogs Horses Dogs Cats Horses Dogs Cats Dogs

SST, UTI SST Resp, SST SST, UTI SST SST, UTI

M31-S1 (2004) M31-S1 (2004) M31-S1 (2004) M31-S1 (2004) VET08 (2018) M31-A2 (2002) M31-A2 (2002) VET08 (2018)

Dogs Cats

Skin, UTI Resp, Skin

VET01S, 3rd ed. (2 (2015) VET01S, 3rd ed. (2 (2015)

SST Resp, SST

VET01S, 3rd ed. (2015) VET01S, 3rd ed. (2015) VET01S, 3rd ed. (2015) M31-A (1999) VET08 (2018) M31-S1 (2004) M31-S1 (2004) VET08 (2018)

Dogs Horses (adults) Horses (foals) Cats Horses Dogs Horses Dogs

SST, UTI

Dogs Horses (adults)

VET01S, 3rd ed. (2015) VET01S, 3rd ed. (2015)

Horses (foals) Dogs

SST

VET01S, 3rd ed. (2015) VET01-A3 (2008)

Cats Dogs

SST, UTI SST

VET08 (2018) VET01-S2 (2013)

Dogs

UTI

VET01S, 3rd ed. (2015)

Cats

SST, UTI

VET01-S2 (2013)

Dogs

Resp, SST, UTI

VET01-S2 (2013)

Dogs Dogs

SST Wds/Absc

VET08 (2018) VET01-A3 (2008)

Cattle Dogs

Mastitis SST

VET01-A3 (2008) VET08 (2018)

Dogs

SST

VET01-S2 (2013)


155

9 / s 9 9 n 1 o i e t i c d n i d S A s t t n n i o e E p m e x k l i p d a e n r p e B u p c S p fi 1 i A c 0 T e E p S - V o y r t a s n n i o r i e i s t e v V e R


For Use With VET01

VET08, 4th ed.

Appendix E. (Continued) Antimicrobial Agent Organism(s) Staphylococcus spp. (Continued) Clindamycin Staphylococcus spp. Difloxacin Staphylococcus spp. Doxycycline S. pseudintermedius S. pseudintermedius Doxycycline S. aureus Enrofloxacin Staphylococcus spp. Enrofloxacin Staphylococcus spp. Enrofloxacin S. aureus Marbofloxacin Staphylococcus spp. Marbofloxacin Staphylococcus spp. Minocycline S. pseudintermedius S. pseudintermedius Minocycline S. aureus Orbifloxacin Staphylococcus spp. Orbifloxacin Staphylococcus spp. Penicillin G Staphylococcus spp. PenicillinS. aureus novobiocin PiperacillinStaphylococcus spp. tazobactam Pirlimycin S. aureus Pradofloxacin S. pseudintermedius S. pseudintermedius Pradofloxacin S. aureus, S. pseudintermedius, S. pseudintermedius, Staphylococcus felis Tetracycline Staphylococcus spp. Streptococcus spp. (36) Amikacin Streptococcus spp. Amikacin Streptococcus equi subsp. equi and equi and subsp. zooepidemicus Amikacin S. equi subsp. equi and equi and subsp. zooepidemicus subsp. zooepidemicus AmoxicillinStreptococcus spp. clavulanate Ampicillin Streptococcus canis (Group G, -hemolytic) Streptococcus spp. Ampicillin Streptococcus spp. Ampicillin S. equi subsp. equi and equi and subsp. zooepidemicus subsp. zooepidemicus Ampicillin Streptococcus suis Cefazolin Streptococcus spp. Streptococcus spp. -hemolytic group Cefazolin Streptococcus spp. Streptococcus spp. -hemolytic group Cefovecin Streptococcus spp. Streptococcus spp. -hemolytic group Cefpodoxime S. canis (Group G, hemolytic) Streptococcus spp.

156

Animal Species

Body Site


Dogs Dogs Dogs Horses Dogs Cats Horses Dogs Cats Dogs Horses Dogs Cats Horses Cattle

SST SST, UTI SST Resp, SST Resp, SST, UTI SST Resp, SST SST, UTI SST SST Resp, SST SST, UTI SST Resp, SST Mastitis

M31-A2 (2002) M31-A2 (2002) VET01S, 3rd ed. (2015) VET08, 4th ed. (2018) M31-A (1999) M31-A (1999) VET08, 4th ed. (2018) M31-S1 (2004) M31-S1 (2004) VET08, 4th ed. (2018) VET08, 4th ed. (2018) M31-A2 (2002) M31-A2 (2002) VET01-S2 (2013) M31-A (1999)

Dogs

SST, UTI

VET08, 4th ed. (2018)

Cattle Dogs Cats

Mastitis Skin, UTI Resp, Skin

M31-A2 (2002) VET01S, 3rd ed. (2 (2015) VET01S, 3rd ed. (2015)

Dogs

SST

VET01S, 3rd ed. (2015)

Dogs Horses (adults)

VET01S, 3rd ed. (2015) VET01S, 3rd ed. (2015)

Horses (foals) Cats

VET01S, 3rd ed. (2015) SST, UTI

VET01-S2 (2013)

Dogs

SST

VET01-A3 (2008)

Cats Horses

SST, UTI Resp

VET08, 4th ed. (2018) VET01-A3 (2008)

Swine Dogs

VET01-S2 (2013) VET01-S2 (2013)

Horses

Resp Gen, Resp, SST, UTI Gen, Resp

Dogs

SST

VET08, 4th ed. (2018)

Dogs

Wds/Absc

VET01-A3 (2008)

©

VET01-S2 (2013)



For Use With VET01

VET08, 4th ed.

Appendix E. (Continued) Antimicrobial Agent Organism(s) Streptococcus spp. (Continued) Ceftiofur S. equi subsp. zooepidemicus Ceftiofur Streptococcus agalactiae Streptococcus dysgalactiae Streptococcus uberis Ceftiofur S. suis Cephalexin Streptococcus spp. Streptococcus spp. -hemolytic group Streptococcus spp. Streptococcus spp. Cephalothin -hemolytic group Clindamycin Streptococcus spp. Streptococcus spp. -hemolytic group Difloxacin Streptococcus spp. Doxycycline S. equi subsp. equi and equi and subsp. zooepidemicus subsp. zooepidemicus Enrofloxacin Streptococcus spp. Enrofloxacin Streptococcus spp. Enrofloxacin S. equi subsp. equi and equi and subsp. zooepidemicus subsp. zooepidemicus Enrofloxacin S. suis Florfenicol S. suis Marbofloxacin Streptococcus spp. Marbofloxacin Streptococcus spp. Minocycline Streptococcus spp. Orbifloxacin Streptococcus spp. Orbifloxacin Streptococcus spp. Penicillin G Streptococcus spp. Penicillin G S. suis PenicillinS. agalactiae novobiocin S. dysgalactiae S. uberis Pirlimycin S. agalactiae S. dysgalactiae S. uberis Pradofloxacin S. canis Tetracycline S. suis Bordetella bronchiseptica (4) Ampicillin B. bronchiseptica bronchiseptica Florfenicol B. bronchiseptica bronchiseptica Tildipirosin B. bronchiseptica bronchiseptica Tulathromycin B. bronchiseptica bronchiseptica Mannheimia haemolytica (12) Ampicillin M. haemolytica haemolytica Ceftiofur M. haemolytica haemolytica Danofloxacin M. haemolytica haemolytica

Enrofloxacin Florfenicol

©

M. haemolytica haemolytica M. haemolytica haemolytica

Animal Species

Body Site


Horses

Resp

M31-S1 (2004)

Cattle

Mastitis

VET01-A3 (2008)

Swine Dogs

Resp SST

M31-A (1999) VET08, 4th ed. (2018)

Dogs

SST

VET01-S2 (2013)

Dogs

SST

VET01-S2 (2013)

Dogs Horses

SST, UTI Resp, SST

M31-A2 (2002) VET08, 4th ed. (2018)

Dogs Cats Horses

Resp, SST, UTI SST Resp, SST

M31-A (1999) M31-A (1999) VET08, 4th ed. (2018)

Swine Swine Dogs Cats Horses Dogs Cats Horses Swine Cattle

Resp Resp SST, UTI SST Resp, SST SST, UTI SST Resp, SST Mastitis

VET01-S2 (2013) M31-S1 (2004) M31-S1 (2004) M31-S1 (2004) VET08, 4th ed. (2018) M31-A2 (2002) M31-A2 (2002) VET01-S2 (2013) VET01S, 3rd ed. (2015) M31-A (1999)

Cattle

Mastitis

M31-A2 (2002)

Cats Swine

Resp, Skin Resp

VET01S, 3rd ed. (2 (2015) VET01-A3 (2008)

Swine Swine Swine Swine

Resp Resp Resp Resp

VET01-S2 (2013) M31-S1 (2004) VET01S, 3rd ed. (2015) VET01-S2 (2013)

Cattle Cattle Cattle

Resp Resp Resp

Cattle Cattle

Resp Resp

VET08, 4th ed. (2018) M31-A (1999) VET08, 4th ed. (2018) – I and R M31-S1 M31-S1 (2004) (2004) – S M31-A (1999) M31-A2 (2002)


157



For Use With VET01

VET08, 4th ed.

Appendix E. (Continued) Antimicrobial Agent Organism(s) Mannheimia haemolytica (Continued) Gamithromycin . haemolytica Penicillin G . haemolytica Spectinomycin . haemolytica Tetracycline . haemolytica Tildipirosin . haemolytica Tilmicosin . haemolytica Tulathromycin . haemolytica Pasteurella multocida (26) Amoxicillin P. multocida clavulanate Ampicillin P. multocida Ampicillin P. multocida Ampicillin P. multocida Cefazolin P. multocida

Cefovecin Cefpodoxime Ceftiofur Ceftiofur Danofloxacin

P. multocida P. multocida P. multocida P. multocida P. multocida

Enrofloxacin P. multocida Enrofloxacin P. multocida Florfenicol P. multocida Florfenicol P. multocida Gamithromycin P. multocida Penicillin G P. multocida Penicillin G P. multocida Pradofloxacin P. multocida Spectinomycin P. multocida Tetracycline P. multocida Tetracycline P. multocida Tildipirosin P. multocida Tildipirosin P. multocida Tilmicosin P. multocida Tulathromycin P. multocida Tulathromycin P. multocida Actinobacillus pleuropneumoniae (10) Ampicillin A. pleuropneumoniae pleuropneumoniae Ceftiofur A. pleuropneumoniae pleuropneumoniae Enrofloxacin A. pleuropneumoniae pleuropneumoniae Florfenicol A. pleuropneumoniae pleuropneumoniae Gentamicin Actinobacillus spp. Tetracycline A. pleuropneumoniae pleuropneumoniae Tiamulin A. pleuropneumoniae pleuropneumoniae Tildipirosin A. pleuropneumoniae pleuropneumoniae Tilmicosin A. pleuropneumoniae pleuropneumoniae Tulathromycin A. pleuropneumoniae pleuropneumoniae

158

Animal Species

Body Site


Cattle Cattle Cattle Cattle Cattle Cattle Cattle

Resp Resp Resp Resp Resp Resp Resp

VET01S, 3rd ed. (2015) VET01-S2 (2013) M31-A2 (2002) VET01-A3 (2008) VET01-S3 (2015) M31-A (1999) VET01-A3 (2008)

Cats

SST, UTI

VET01-S2 (2013)

Cats Cattle Swine Dogs

VET08, 4th ed. (2018) VET08, 4th ed. (2018) VET01-S2 (2013) VET01-S2 (2013)

Cats Dogs Cattle Swine Cattle

SST, UTI Resp Resp Gen, SST, Resp, UTI SST, UTI Wds/Absc Resp Resp Resp

Cattle Swine Cattle Swine Cattle Cattle Swine Cats Cattle Cattle Swine Cattle Swine Swine Cattle Swine

Resp Resp Resp Resp Resp Resp Resp Skin, Resp Resp Resp Resp Resp Resp Resp Resp Resp

Swine Swine Swine Swine Horses Swine Swine Swine Swine Swine

Resp Resp Resp Resp

©

Resp Resp Resp Resp Resp

VET08, 4th ed. (2018) VET01-A3 (2008) M31-A (1999) M31-A (1999) VET08, 4th ed. (2018) – I and R M31-S1 M31-S1 (2004) (2004) – S M31-A (1999) VET01-S2 (2013) M31-A2 (2002) M31-S1 (2004) VET01S, 3rd ed. (2015) VET01-S2 (2013) VET01S, 3rd ed. (2015) VET01S, 3rd ed. (2 (2015) M31-A2 (2002) VET01-A3 (2008) VET01-A3 (2008) VET01S, 3rd ed. (2015) VET01S, 3rd ed. (2015) M31-A2 (2002) VET01-A3 (2008) VET01-S2 (2013) VET01-S2 (2013) M31-A (1999) VET01-S2 (2013) M31-S1 (2004) VET01-S2 (2013) VET01-A3 (2008) M31-A (1999) VET01S, 3rd ed. (2015) M31-A2 (2002) VET01-S2 (2013)



For Use With VET01

VET08, 4th ed.

Appendix E. (Continued) Antimicrobial Agent Organism(s) Histophilus somni (10) Ampicillin H. somni Ceftiofur H. somni Enrofloxacin H. somni Florfenicol H. somni Gamithromycin H. somni Penicillin G H. somni Spectinomycin H. somni Tetracycline H. somni Tildipirosin H. somni Tulathromycin H. somni

Animal Species

Cattle Cattle Cattle Cattle Cattle Cattle Cattle Cattle Cattle Cattle

Body Site

Resp Resp Resp Resp Resp Resp Resp Resp Resp Resp


VET08, 4th ed. (2018) M31-A (1999) M31-A (1999) M31-A2 (2002) VET01S, 3rd ed. (2015) VET01-S2 (2013) M31-A2 (2002) VET01-A3 (2008) VET01S, 3rd ed. (2015) VET01-A3 (2008)

Abbreviations: gen, genital; GWG, Generic Drug Working Group; I, intermediate; R, resistant; resp, respiratory; SST, skin and soft tissue; UTI, urinary tract infection; wds/absc, wounds and/or abscesses. *

Past editions of the standard (with breakpoint tables included) and supplement include: M31-A (June 1999), M31-A2 (May 2002), M31-S1 (May 2004), VET01-A3 (February 2008), VET01-S2 (July 2013), and VET01S, 3rd ed. (June 2015). † Although canine breakpoints are not available for oxacillin and chloramphenicol, minimal inhibitory concentration distribution data from canine isolates were evaluated by the subcommittee and determined to support human breakpoints for oxacillin against S. pseudintermedius and pseudintermedius and S. schleiferi (see schleiferi (see Table 2C), and h uman breakpoints for chloramphenicol against Enterobacteriaceae against Enterobacteriaceae (see (see Table 2A), Staphylococcus spp. (see Table 2C), Streptococcus spp. Streptococcus spp. (see Table 2D), Enterococcus spp. Enterococcus spp. (see Table 2E), and P. multocida (see multocida (see Table 2H).

©


159



For Use With VET01

VET08, 4th ed.

Glossary I. Antimicrobial Class and Subclass Designations, Antimicrobial Agents, and Antimicrobial Resistance Mechanisms I y r a s s o l G

Antimicrobial Class Aminocyclitols

Antimicrobial Subc Subcla lass ss(e (es) s)

Aminoglycosides

Ansamycin -lactam combination agents Cephems

Amikacin Gentamicin Kanamycin Neomycin Streptomycin Tobramycin Rifampin Amoxicillin-clavulanate Piperacillin-tazobactam Cephalosporin Ia,b

Cephalosporin IIa,b Cephalosporin IIIa,b

Cephalosporin IVa,b Cephamycinc Carbapenems

Monobactams Folate pathway antagonists

Glycopeptides Lincosamides

160

Anti Antimi micr crob obia iall Agen Agent( t(s) s) Apramycin Spectinomycin

Glycopeptide Lipoglycopeptide

Cefadroxil Cefazolin Cephalexin Cephalothin Cephapirin Cefaclor Cefuroxime Cefoperazone Cefotaxime Cefovecin Cefpodoxime Ceftazidime Ceftiofur Ceftriaxone Cefepime Cefquinome Cefotetan Cefoxitin Doripenem Ertapenem Imipenem Meropenem Aztreonam Ormetoprim Sulfonamides Trimethoprim Trimethoprimsulfamethoxazole Vancomycin Teicoplanin Clindamycin Lincomycin Pirlimycin

©

Anti Antimi micr crob obia iall Resi Resist stan ance ce Mech Mechan anis ism m Enzymatic modification Efflux Target site (ribosome) mutation Enzymatic modification Decreased permeability Target site (ribosome) modification/ mutation Efflux

Target (RNA poly merase) mutation Enzymatic inactivation (-lactamases) Enzymatic inactivation (-lactamases) Decreased permeability Altered penicillin-binding proteins Efflux

Decreased permeability Production of drug-insensitive enzymes Overexpression of sensitive enzymes Efflux Target site (cell wall) modification Target site (ribosome) modification/mutation Enzymatic inactivation Efflux Ribosomal rotection



For Use With VET01

VET08, 4th ed.

Glossary I. (Continued) Antimicrobial Class Macrolides:

Antimicrobial Subc Subcla lass ss(e (es) s)

Anti Antimi micr crob obia iall Agen Agent( t(s) s)

14-membered rings

Clarithromycin Erythromycin

15-membered rings

Azithromycin Gamithromycin Tulathromycin

16-membered rings

Spiramycin Tildipirosin Tilmicosin Tylosin Tylvalosin Metronidazole Avilamycin Penicillin Amoxicillin Ampicillin Piperacillin Methicillin Nafcillin Oxacillin Chloramphenicol Florfenicol

Nitroimidazoles Orthosomycins Penicillinsd (penicillinaselabile) Penicillinsd

Penicillind Aminopenicillind Ureidopenicillind Penicillinae-stable penicillinse

Phenicols

Pleuromutilins

Tiamulin Valnemulin

Polyether ionophore Polypeptides

Monensin Narasin Bacitracin Polymyxin Nalidixic acid

Quinolones

Quinolone Fluoroquinolone

©

Ciprofloxacin Danofloxacin Difloxacin Enrofloxacin Marbofloxacin Orbifloxacin Pradofloxacin


Anti Antimi micr crob obia iall Resi Resist stan ance ce Mech Mechan anis ism m Target site (ribosome) modification/ mutation Decreased permeability Enzymatic inactivation Efflux

Altered drug-activating enzymes enzymes Decreased ribosomal binding Reduced permeability Altered penicillin-binding proteins Enzymatic inactivation (β-lactamases) Efflux Target site (ribosome) modification/mutation Decreased permeability Enzymatic inactivation Efflux Ribosomal protection Target site (ribosome) modification/mutation Decreased permeability Efflux Ribosomal protection Not known Lipopolysaccharide modification Efflux Target (DNA gyrase, Topoisomerase IV) mutation Decreased permeability Efflux Target site protection Enzymatic inactivation

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Glossary I. (Continued)

I y r a s s o l G

Antimicrobial Class Streptogramins: Streptogramins A

Streptogramins B

Antimicrobial Subc Subcla lass ss

Anti Antimi micr crob obia iall Agen Agents ts

Virginiamycin M (I) Virginiamycin S

Anti Antimi micr crob obia iall Resi Resist stan ance ce Mech Mechan anis ism m Target site (ribosome) modification/mutation Enzymatic inactivation Efflux Ribosomal protection

Combinations

Virginiamycin M-virginiamycin S = virginiamy virginiamycin cin Tetracyclines Chlortetracycline Efflux Doxycycline Target site (ribosome) Minocycline modification/mutation Oxytetracycline Drug detoxification Tetracycline Ribosomal protection Others Nitrofurantoin Novobiocin Abbreviations: DNA, deoxyribonucleic acid; MRSA, methicillin-resistant methicillin-resistant Staphylococcus aureus; RNA, ribonucleic acid. Footnotes

a.

Cephalosporins I, II, III, and IV are sometimes referred to as first-, second-, third-, and fourth-generation cephalosporins, respectively. Cephalosporins III and IV are also referred to as “extended-spectrum cephalosporins.” This does not imply activity against ESBL-producing gram-negative bacteria.

b.

For all confirmed extended-spectrum -lactamase (ESBL)–producing strains, the test interpretation should be reported as resistant for this antimicrobial class or subclass.

c.

Although often referred to as a second-generation cephalosporin, cephamycins are not included with the other cephalosporins with regard to reporting of ESBL-producing strains.

d.

Penicillinase-labile; Penicillinase-labile; hydrolyzed by staphylococcal penicillinase.

e.

Not hydrolyzed by staphylococcal penicillinase. penicillinase.

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Glossary II. Abbreviations Commonly Used for Antimicrobial Agents Incorporated Into Disks or Susceptibility Panels I I y r a s s o l G

Antimicrobial Agent Amikacin Amoxicillin-clavulan Amoxicillin -clavulanate ate Ampicillin Apramycin Avilamycin

Abbreviation(s) AN, AK, Ak, AMI, AMK AMC, A/C, AXC, Aug, AUG, XL, AML, AMOX/CA AM, Am, AMP, AP, ABPC AP, APR AVI

Cefazolin

CZ, CFZ, Cfz, FAZ, KZ, CEZ, CFAZ

Cefovecin Cefoxitin Cefpodoxime Cefpodox ime

VEC, FOV FOX, CX, Cfx, FX, CFX, CFOX, COX CPD, Cpd, POD, PX

Cefquinome Ceftazidime Ceftiofur Cephalexin Cephalothin Cephaloth in Chloramphenicol Chloramphe nicol

CEQ CAZ, Caz, TAZ, Tz XNL, FUR, CEF, ACC, TIO CN, LEX, CFL, CX, CFX, CL, CLEX, CEX CF, Cf, CEP, CE, KF, CET, CEF, CTIN, CTN C, CHL, CL, CP, CMP

Chlortetracycline

CTET

Clarithromycin

CLA, CLR, CLM, Cla, CH

Clindamycin

CC, CD, CM, Cd, CLI, DA, CLDM

Danofloxacin Difloxacin

DAN5, DAN, DANO DIC, DIF, DF

Doxycycline

DOXY

Enrofloxacin Enrofloxa cin

ENO, ENR, ENF, EFX, ENRO, EF

Erythromycin Erythromyc in

E, ERY, EM

Florfenicol Florfenico l Gamithromycin Gentamicin Imipenem Kanamycin

FFC, FFN GAM GM, GMS, HLG, Gm, GmS, GEN, CN IPM, IMI, Imp, IP, IMIP K, KAN, HLK, KM

Kanamycin-cephalex Kanamycin- cephalexin in

K/C, K/CXN, KAN/C

Marbofloxacin Monensin Narasin Orbifloxacin Orbifloxa cin Oxacillin Penicillin Penicillin-novobio Penicillin- novobiocin cin Piperacillin Piperacillin-tazobactam Pirlimycin Polymyxin B Pradofloxacin Rifampin Spectinomycin Spectinomy cin

MAR 5, MAR, MARBO MON NAR OBX, ORB OX, OXS, Ox, OXA, MPIPC, OXAC P, PEN, PG, PCG, PENG P/NB, P/NOV, P/N PIP, PI, PP, Pi TZP, PZT, P/T, PTc PRL, PIRL PB PRA RA, RI, RIF, Rif, RD, RP, RFP, RAM SPT, SPE, SC, SH, SPC

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Glossary II. (Continued) Sulfisoxazole Sulfisoxa zole Tetracycline Tetracycl ine Tiamulin Tildipirosin Tilmicosin

Antimicrobial Agent

Agent Abbreviation(s) G, FIS, SF Te, TE, TET, TC, T TIA TIP TIL, TMS

Tobramycin Trimethoprim-sulfamethoxazole

NN, TM, TO, To, TOB SXT, Sxt, T/S, STG, TS, ST

Tulathromycin Tylosin Vancomycin

TUL TYL, TYLB, TYLT, TY, TLS Va, VA, VAN, VCM

I I y r a s s o l G

NOTE: Designations for antimicrobial agents that are also used in human medicine are in CLSI document M100. M100 .1 Reference for Glossary II 1

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Glossary III. List of Identical Id entical Abbreviations Used for More Than One Antimicrobial An timicrobial Agent in US Diagnostic Products I I I y r a s s o l G

Listed below are some known abbreviations used for more than one antimicrobial agent. It cannot be assumed that the list is exhaustive, and some agents may no longer be available. Abbreviation

Antimicrobial Agents for Which Respective Abbreviation Is Used

AZ

Azithromycin, azlocillin

AZM CD, Cd CF, Cf CFM, Cfm CFR, Cfr CFX, Cfx CH CL CM CN, Cn CP, Cp CPZ CZ, Cz DX NIT SC SO TC

Azithromycin, aztreonam Clindamycin, cefdinir Cefaclor, cephalothin Cefixime, cefamandole Cefaclor, cefadroxil Cefoxitin, Cefoxitin , cefuroxime Clarithromycin, Clarithromycin, cephradine Cephalothin, chloramphenicol Clindamycin, cefamandole Cephalexin, cefotetan, cinoxacin, gentamicin Cephapirin, cefoperazone, ciprofloxacin Cefprozil, cefoperazone Ceftizoxime, cefazolin Doxycycline, dicloxacillin Nitazoxanide, nitrofurantoin nitrofurantoin Spectinomycin, methicillin Sparfloxacin, oxacillin Tetracycline, ticarcillin

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The Quality Management System Approach Clinical and Laboratory Standards Institute (CLSI) subscribes subscribes to a quality management system (QMS) approach in the development of standards and guidelines that facilitates project management, management, defines a document structure using a template, and provides a process to identify needed documents. The QMS approach applies a core set of “quality system essentials” (QSEs), basic to any organization, to all operations in any health care service’s path of workflow (ie, operational aspects that define how a particular product or service is p rovided). The QSEs provide the framework for delivery of any type of product or service, serving as a manager’s guide. The QSEs are: Orga Organi niza zati tion on Custo ustom mer Foc Focus Facili Facilitie tiess and Safety Safety

Pers Person onne nell Purc Purcha hasi sing ng and Inve Invent ntor ory y Equipm Equipment ent

Proc Proces esss Mana Manage geme ment nt Doc Documen umentts and Record cordss Inform Informati ation on Manag Manageme ement nt

Nonc Noncon onfo form rmin ing g Even Eventt Mana Manage geme ment nt Asse Assesssme sments nts Contin Continual ual Improv Improveme ement nt

VET08 covers the QSE indicated by an “X.” For a description of the other documents listed in the grid, please refer to the Related CLSI Reference Materials section.

n o i t a z i n a g r O

s u c o F r e m o t s u C

d n a y s t e e i f t i a l i S c a F

l e n n o s r e P

d n a y r g o n t i n s e a h v n c I r u P

t n e m p i u q E

t n e s s m e e c g o a r n P a M

d n a s s d t r n o e c m e u c R o D

t n n o e i t m a e m g r a o n f a n I M

t n g e n m i e m g r a o n f n a o M c n t o n e N v E

s t n e m s s e s s A

t l n a e u m n e i t v n o o r C p m I

X EP23 M02 M07 M11 M23 M39 M45 M100 VET01 VET02 VET05 VET06

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Path of Workflow

A path of workflow is the description of the necessary processes to deliver the particular product or service that the organization or entity provides. A laboratory path of workflow consists of the sequential processes: preexamination, preexamination, examination, and postexamination and their respective sequential subprocesses. All laboratories follow these processes to deliver their services, namely quality laboratory information. information. VET08 covers the medical laboratory path of workflow processes indicated by an “X.” For a description of the other documents listed in the grid, please refer to the Related CLSI Reference Materials section. Preexaminatio n

n o g i t n a i n r i e m d a r x o E

n o i t c e l l o c e l p m a S

t r o p s n a r t e l p m a S

Examination g n i s s e e l c p o m r p a / S t p i e c e r

n o i t a n i m a x E

EP23 M02 M07 M11

VET01

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d n a w p u e i v w e o r l s l t o l f u s e R

Postexamina tion

n o i t a t e r p r e t n I

X EP23 M02 M07 M11

X EP23 M02 M07 M11

M45 M100 VET01 VET06

M45 M100 VET01 VET06


g n g i t n r i o i v p h e r c r s a t l u d s n e a R

t n e m e g a n a m e l p m a S

X M02 M07 M11 M39 M45 M100 VET01 VET06

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Related CLSI Reference Materials



EP23™

Laboratory Laboratory Quality Control Based on Risk Management. 1st ed., 2011. This document provides guidance based on risk management management for laboratories laboratories to develop develop quality control plans tailored to the particular particular combination of measuring system, laboratory setting, and clinical application of the test.

M02

Performance Performance Standards for Antimicrobial Antimicrobial Disk Susceptibility Tests. 13th ed., 2018. This standard covers the current recommended methods for d isk susceptibility testing and criteria for qu ality control testing.

M02QG

Disk Diffusion Reading Guide. 1st ed., 2018. The Disk Diffusion Reading Guide provides photographic examples of the proper method for reading disk diffusion susceptibility testing results.

M07

Methods for Dilution Antimicrobial Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. Aerobically. 11th ed., 2018. This standard covers reference methods for determining minimal inhibitory concentrations of aerobic bacteria by broth macrodilution, macrodilution, broth microdilution, and agar agar dilution.

M11

Methods for Antimicrobial Antimicrobial Susceptibility Testing of Anaerobic Bacteria. 8th ed., 2012. This standard provides reference methods for the determination of minimal inhibitory concentrations concentrations of anaerobic bacteria by agar dilution and broth microdilution.

M23

Development of In V itro Susceptibility Testing Criteria and Quality Control Parameters. 5th ed., 2018. This guideline discusses the necessary and recommended data for selecting appropriate breakpoints and quality control ranges for antimicrobial agents.

M39

Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data. 4th ed., 2014. This document describes methods for recording and analysis of antimicrobial susceptibility test data, consisting of cumulative and ongoing summaries of susceptibility patterns of clinically significant microorganisms.

M45

Methods for Antimicrobial Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria. 3rd ed., 2016. This guideline informs clinical, public health, and research laboratories on susceptibility testing of infrequently isolated or fastidious bacteria that are not included in CLSI documents M02, M07, or M100. Antimicrobial agent selection, test interpretation, and quality control are addressed.

M100

Performance Standards for Antimicrobial Antimicrobi al Susceptibility Susceptib ility Testing. 28th ed., 2018. This document includes updated tables for the Clinical and Laboratory Standards Institute antimicrobial susceptibility testing standards M02, M07, and M11.

VET01

Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals. 5th ed., 2018. This standard covers the current recommended methods for disk diffusion susceptibility testing and the reference methods for determining minimal inhibitory concentrations of aerobic bacteria by broth microdilution, microdilution, broth macrodilution, and agar dilution dilution for veterinary use.

VET02

Development of In Vit ro Susceptibility Testing Criteria and Quality Control Parameters for Veterinary Antimicrobial Antimicrobial Agents. 3rd ed., 2008. This document addresses the required and recommended data needed for selection of appropriate interpretive standards and quality control guidance for new veterinary antimicrobial agents.

VET05

Generation, Presentation, and Application of Antimicrobial Susceptibility Test Data for Bacteria of Animal Origin. 1st ed., 2011. This report offers guidance on areas in which harmonization can be achieved in veterinary antimicrobial surveillance programs with the intent of facilitating comparison of data among surveillance programs.

VET06

Methods for Antimicrobial Antimicrobial Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria Isolated From Animals. 1st ed., 2017. This document provides guidance for antimicrobial agent disk and dilution susceptibility testing, criteria for quality control testing, and breakpoints for fastidious and infrequently tested bacteria for veterinary veterinary use.

CLSI documents are continually reviewed and revised through the CLSI consensus process; therefore, readers should refer to the most current editions.



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