ACUTE UNCOMPLICATED UNCOMPLICATED PYELONEPHRITIS IN WOMEN
1. When is acute uncomplicated pyelonephritis suspected? In otherwise healthy women with no clinical or historical evidence of anatomic or functional urologic abnormalities, the classic syndrome of acute uncomplicated pyelonephritis (AU!" is characteri#ed by fever ($%&' ", chills, flan) pain, costovertebral angle tenderness, nausea and vomiting, with or without signs and symptoms of lower urinary tract infection *+ubin 1-. /aboratory findings include pyuria (% 0 wbchpf of centrifuged urine" on urinalysis and bacteriuria with counts of % 12,222 cfu of a uropathogenml on urine culture *+oberts 1'3, +ubin 1-. -. What are the recommended diagnostic tests for acute uncomplicated pyelonephritis? Urinalysis and 4ram stain are recommended (4rade 5". Urine culture and sensitivity test should also be performed routinely to facilitate costeffective use of antimicrobial agents because of the potential for serious se6uelae if an inappropriate antimicrobial antimicrobial regimen is used (4rade 5". °
Summary of evidence evidence Benefits: No studies have directly directly addressed addressed the diagnostic utility utility of urine urine culture and sensitivity sensitivity and urine gram stain in AUPN. However, these tests are recommended because treatment options are simplified if if a likely pathogen pathogen is established. established. Differentiating Differentiating between between grampositive grampositive and gramnegative gramnegative pathogens can guide optimal empiric empiric antibiotic selection and minimi!e minimi!e the conse"uences conse"uences of inappropriate inappropriate choice in terms of cost, resistance and adverse drug reactions. A randomi!ed clinical trial #$alan %&&&' comparing ciproflo(acin with $)P*)+ provides indirect evidence that treatment outcomes are better when the antibiotic regimen is active against the patients organism. -acteriologic and clinical failure rates are significantly higher if the patient is receiving antibiotics to which the organism is resistant. )ean cost per cure was also higher by %/ for $)P*)+ treated patients because they re"uired more interventions and a change in antibiotic regimen.
5lood cultures are not routinely recommended (4rade 7". 5lood cultures done twice are recommended for patients who present with signs of sepsis defined as presence of any two of the following8 temperature %&' 2 or 9 &32, leu)openia (W59 :,222" or leu)ocytosis (W5 % 1-,222", tachycardia (;+%2 beatsmin", tachypnea (++% -2min or a<- 9&-mm;g", or hypotension (=59 2mm;g or %:2mm;g drop from baseline" (4rade ". Summary of evidence evidence prospective study #0e #0elasco lasco %&&1' of 21 women women with clinical clinical symptoms of AUPN AUPN that assessed assessed Benefits: A prospective the utility of blood cultures cultures showed that discordant cases 3different 3different organisms isolated in blood and urine4 were found in only %.5/. 6linical and microbiologic outcomes did not differ between these cases and the rest of the patients studied. No changes of antibiotic treatment were needed based on blood culture results. An earlier retro retrospective spective chart review #)c)urray 7889' 7889' of 1&7 patients with with AUPN showed similar similar results. results. :nly 72/ had positive blood cultures with only one patient having a discordant result that did not re"uire a change in antibiotic regimen.
&. $reatment &.1 an patients with acute uncomplicated pyelonephritis be treated as outpatients? !on>pregnant patients with no signs and symptoms of sepsis, who are are li)ely to adhere to treatment and return for follow>up, may be treated as outpatients (4rade 5". An initial parenteral dose of ceftriaone may be given followed by an oral antibiotic (4rade 5".
Benefits: ;e found no <6$s directly comparing inpatient versus outpatient management. $he feasibility however of outpatient therapy re"uires demonstration that oral antibiotic is as effective as parenteral. ;e found % <6$s comparing oral versus =0 antibiotics. A multicenter randomi!ed double blind trial #)ombelli 7888' compared oral ciproflo(acin && mg -=D versus =0 ciproflo(acin %&& mg " 7% hrs in 757 patients with acute pyelonephritis, community ac"uired U$= and hospital ac"uired U$=. Patients with severe sepsis, unable to take oral medication or had renal obstruction or renal foci of suppuration, were e(cluded from the study. *ubgroup analysis of those with severe pyelonephritis 3N>??4 showed that mean duration of fever was similar for both oral and =0 ciproflo(acin 3%.% days, 8/ 6= 7.9 to %.? vs %.? days, 8/ 6= % to 1.%@ p>&.724. )icrobiologic failure at 1 days of treatment was also not statistically different, 1/ oral ciproflo(acin vs. %/ =0 ciproflo(acin 3<< 7.8%, 8/6= &.72 to %&.94. =n another randomi!ed open trial #*anche! %&&%', single dose =0 ceftria(one followed by cefi(ime 5&& mg :D 3N>54 was compared with standard treatment of =0 ceftria(one 7 gram daily maintained until culture results are out followed by an oral antibiotic 3N>74. -oth groups remained hospitali!ed until they became afebrile and urine culture was out but during hospitali!ation no other treatment was given that could not have been accomplished at home. 6linical cure 387/ vs 8%/@ << &.2 8/6= &.%5%.824 and microbiologic eradication after 1 days of treatment 37&&/ for both groups4 did not differ significantly.
&.- What drugs can be used for empiric treatment of acute uncomplicated pyelonephritis? =everal effective regimens (fluoro6uinolones, aminoglycosides, & rd -nd generation cephalosporins, etended spectrum penicillins" are recommended (4rade A". (See Table 6) $he aminopenicillins (ampicillin or amoicillin" and first generation cephalosporins are not recommended because of the high prevalence of resistance and increased recurrence rates in patients given these beta>lactams (4rade B". 5ecause of high resistance rates to $C>=CD (See Table 5), this drug is not recommended for empiric treatment (4rade B" but can be used when the organism is susceptible on urine culture and sensitivity. ombining ampicillin with an aminoglycoside offers no added benefit, ecept when enterococcal infection is suspected (4rade ". IE antibiotics can be shifted to any of the listed oral antibiotics (Table 6) once the patient is afebrile and can tolerate oral drugs (4rade 5". $he choice of continued antibiotic therapy should be guided by the urine culture and sensitivity results once available (4rade 5". $able 3. Bmpiric treatment regimens for uncomplicated acute pyelonephritis Antibiotic and 7ose Fre6uency and 7uration OR! Ofloxacin 400 mg BID; 14 days Ciprofloxacin 500mg BID; 7-10days Gatifloxacin 400 mg OD; 7-10 days L!ofloxacin "50 mg OD; 7-10 days Cfixim 400 mg OD; 14 days Cf#roxim 500 mg BID; 14 days $moxicillin-cla!#lanat %"5 mg &'(n gram stain s(o's gram positi! organisms) *ID; 14 days "R#$T#R! &gi!n #ntil patint is af+ril) Cftriaxon 1-"gm , "4
Ciprofloxacin "00-400mg , 1" L!ofloxacin "50-500 mg , "4 Gatifloxacin 400 mg , "4 Gntamicin -5 mg./g B &.-ampicillin) , "4 $mpi-s#l+actam 125 gm &if 'it( gram positi! organisms on gram stain) ,% 3ipracillin- tao+actam "2"5 425 gm ,%-6 Summary of evidence $here is relative paucity of wellcontrolled trials comparing the efficacy of various antibiotic regimens in acute uncomplicated pyelonephritis. $he recommended regimens in $able ? have comparable efficacy, provided the organism is susceptible. $he recommendations have taken into consideration the limitations of local reports on sensitivity patterns and are not meant to e(clude other effective regimens. Bor instance, aminoglycosides other than gentamicin may be used such as amikacin. $he choice of empiric antimicrobial should largely be based on the epidemiological information available to the physicians in their locality. $he =D*A clinical practice guideline committee found 8 studies on pyelonephritis, of which were <6$s. A systematic review #;arren 7888' of the four <6$s also confirmed the suboptimal outcomes of treatment with ampicillin or ampicillinlike compounds because of high resistance rates and, increased recurrence rates even with susceptible organisms compared with $)P*)+. *ubse"uent studies on newer fluoro"uinolones not included in the =D*A review using ciproflo(acin as comparator have shown similar clinical cure and bacteriologic eradication rates as described below. %luoro&uinolones Benefits: :ne <6$ #6o( %&&%' on 19% adults with complicated and uncomplicated pyelonephritis compared gatiflo(acin 5&& mg :D or ciproflo(acin && mg -=D both for 97& days. Bor those with AUPN, bacteriologic cure rates 8 days post therapy did not differ significantly 38%/ for gatiflo(acin versus 2/ for ciproflo(acin4. 6linical cure rates, likewise, were not significantly different at 577 days post therapy 37&&/ for gatiflo(acin and 8/ for ciproflo(acin4 and at %& days post therapy 322/ for gatiflo(acin and 8/ for ciproflo(acin4.
Comments: $he results of the gatiflo(acin #6o( %&&%' and levoflo(acin #&.8%4. An open, randomi!ed trial comparing cefuro(ime %& mg -=D and oflo(acin %&& mg -=D for 7& to 7% days in 71 adult outpatients with AUPN showed no significant difference in clinical cure rates 38%/ for cefuro(ime and 85/ for oflo(acin4 #Naber 7882'. No clinical trials were found on the effectiveness of first generation cephalosporins for acute uncomplicated pyelonephritis. Comments: -ecause of the increasing resistance to $)P*)+ despite the lack of generali!able local data on resistance rates of F.coli, $)P*)+ is no longer recommended as a first line drug in the empiric treatment of AUPN because it is a potentially serious infection with serious se"uelae.
&.& What is the effective duration of treatment for acute uncomplicated pyelonephritis? $he recommended duration of treatment is 1: days. =elected fluoro6uinolones (see Table 6) can be given for G>12 days (4rade A". Summary of evidence Benefits: $he =D*A guidelines recommend % weeks of therapy for AUPN based on a review of 5 <6$s #;arren 7888'. =n a <6$ #$alan %&&&' of % women comparing oral ciproflo(acin && mg -=D vs $)P*)+ 7?&G2&& mg -=D in an outpatient setting, clinical and bacteriologic cure rates 577 days post therapy were significantly higher with 9day ciproflo(acin compared to 75day $)P*)+. 6linical cure rate for ciproflo(acin was 8?/ versus 21/ for $)P*)+ 3<< 7.7?@ 8/ 6= 7.&? to 7.%24. -acteriologic cure rates were 88/ for ciproflo(acin and 28/ for $)P*)+ 3<< 7.77, 8/ 6= 7.&5 to 7.784. *ustained clinical cure rate %%52 days post therapy was higher at 2%/ for ciproflo(acin vs 9%/ for $)P*)+ 3<< 7.75, 8/ 6= 7.&7 to 7.%24. *ustained bacteriologic cure rates were 25/ for ciproflo(acin and 95/ for $)P*)+ 3<< 7.75, 8/ 6= 7.&7 to 7.%24. Adverse drug events were less with ciproflo(acin 3%5/4 compared to 11/ for $)P*)+ 3<< &.91, 8/ 6= &.1 to7.&4.
:. Who will re6uire wor) up for urologic abnormalities? +outine urologic evaluation and routine use of imaging procedures are not recommended (4rade 7". onsider radiologic evaluation if the patient remains febrile within G- hours of treatment or if with recurrence of symptoms to rule out the presence of nephrolithiasis, urinary tract obstruction, renal or perinephric abscesses or other complications of pyelonephritis (4rade ".
0. Is a follow up urine culture recommended? In patients who are clinically responding to therapy (usually apparent in 9 G- hours after initiation of treatment", a follow>up urine culture is not necessary (4rade ". +outine post>treatment cultures in patients who are clinically improved are also not recommended (4rade ". In women whose symptoms do not improve during therapy and in those whose symptoms
recur after treatment, a repeat urine culture and sensitivity test should be performed (4rade ". Summary of evidence: $he above recommendations are based on e(pert opinion consensus. ;e did not find any studies demonstrating the clinical utility of followup urine cultures during treatment and post treatment of patients who are responding to therapy. =n patients not improving, it is necessary to repeat the urine culture and sensitivity to rule out antibiotic resistance.
3. What is the recommended management for patients whose symptoms recur? +ecurrence of symptoms re6uires antibiotic treatment based on rine culture and sensitivity test results, in addition to assessing for underlying genitourologic abnormality (4rade ". $he duration of re>treatment in the absence of a urologic abnormality is - wee)s (4rade ". For patients whose symptoms recur and whose culture shows the same organism as the initial infecting organism, a :>3 wee) regimen is recommended (4rade ". Summary of evidence: ;e did not find any randomi!ed controlled trials that determined the optimum duration of treatment for women with recurrent pyelonephritis. III. ASYMPTOMATIC BACTERIURIA IN ADULTS
1. When