Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux (strength of recommendation: B, based on poor-quality or inconclusive cohort and randomized controlled studies). No controlled, prospective studies have examined the effectiveness of prophylactic antibiotics to prevent UTI recurrence or renal scarring

Reed, Lane

Shakil, Amer

Wilder, Laura

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C L I N I C A L  I N Q U I R I E S498 JUNE 2004 / VOL 53, NO 6 · The Journal of Family PracticeC O N T I N U E Dsurveillance for varicella vaccine. JAMA 2000;284:1271–1279.7. Gershon AA, LaRussa P, Steinberg S. The varicella vac-cine. Clinical trials in immunocompromised individuals.Infect Dis Clin North Am 1996; 10:583–594.8. Levin MJ, Gershon AA, Weinberg A, et al. Immunization ofHIV-infected children with varicella vaccine. J Pediatr2001; 139:305–310.9. Rothberg M, Bennish ML, Kao JS, Wong JB. Do the bene-fits of varicella vaccination outweigh the risks? A deci-sion-analytical model for policymakers and pediatricians.Clin Infect Dis 2002; 34:885–894.10. American Academy of Family Practice. Periodic HealthExaminations. Revision 5.3. Leawood, Kansas: AAFP; 2002.11. American Academy of Pediatrics. Committee on InfectiousDiseases. Varicella vaccine update. Pediatrics 2000;105:136–141.■ CLINICAL COMMENTARYEncourage varicella vaccination, except for the immunocompromisedFor many parents, vaccination decisions aremade based on school district requirements.Varicella zoster vaccine is an exception to thatrule. Parents can choose to immunize theirchild at 12 months or wait and let nature takeits course—hopefully before the child startskindergarten. The major concern with the vac-cine has been its long-term efficacy. Althoughno one knows for sure how long immunity issustained, studies show that detectable anti-bodies are present for up to 20 years. As a parent and physician, my decision tovaccinate my daughter was made after I wit-nessed an 8-year-old boy in the emergencyroom with respiratory distress secondary tocomplications from chickenpox. This experi-ence reinforced for me that chickenpox is a life-threatening disease. The effects of chickenpoxinclude scarring as well as time away fromwork for parents. I therefore encourage vari-cella vaccination for my patients, with the onlyexception being those who are immunocompro-mised, for whom we have no data. To the question of whether we should we vac-cinate children to prevent chickenpox, I give aresounding “yes.”Kristen Rundell, MD, University of Colorado HealthSciences Center, DenverDo antibiotics preventrecurrent UTI in children with anatomic abnormalities?■ EVIDENCE-BASED ANSWEREvidence is insufficient to recommend for oragainst antibiotic prophylaxis to prevent recur-rent urinary tract infections (UTI) in children withanatomic abnormalities. Guidelines acknowledgethis lack of evidence, but still recommend usingprophylactic antibiotics in children with vesicu-loureteral reflux (strength of recommendation: B,based on poor-quality or inconclusive cohort andrandomized controlled studies).1–3 No controlled,prospective studies have examined the effective-ness of prophylactic antibiotics to prevent UTIrecurrence or renal scarring. ■ EVIDENCE SUMMARYRecommendations about antibiotic prophylaxisare based on several premises. Reflux predispos-es children to acute pyelonephritis; reflux plusinfection leads to reflux nephropathy and ulti-mately to renal scarring. In theory, if antibioticscould be initiated at the appropriate time and bemaintained until reflux resolves, we could suc-cessfully prevent infection and scarring.4A recent systematic review evaluated the useof antibiotics to prevent UTI in children.5 Thisreview of 5 randomized controlled trials includeda total of 463 children between the ages of 2months to 16 years. Three out of 5 trials evaluat-ed the effectiveness of antibiotic treatment for 2to 6 months to prevent subsequent off-treatmentrecurrence. The 2 smaller trials (n=71) evaluatedthe use of low-dose long-term antibiotics to pre-vent UTI. There was a clinically, but not statistically,significant trend towards reduced risk of UTIduring long-term antibiotic treatment (riskreduction [RR]=0.31; 95% confidence interval[CI]=0.10–1.00); however, no sustained benefitwas seen once antibiotics were stoppedC L I N I C A L  I N Q U I R I E SJUNE 2004 / VOL 53, NO 6 · The Journal of Family Practice 499C O N T I N U E Dalthough a clinically important effect has not beenexcluded, the regular use of antimicrobial prophy-laxis for most patients who have neurogenic bladder caused by spinal cord dysfunction is notsupported at this time.8Poor compliance may be an issue with long-term prophylaxis and may represent patient orparent practice.9One study found that in childrentaking low-dose trimethoprim, 97% of the parentsreported giving antibiotics on daily basis, but in31% of subjects, trimethoprim was not detectablein the urine.6 Risk of prophylaxis includes nausea,vomiting, and rash in 8% to 10% of patients; devel-opment of resistant organisms; and change inindigenous microflora.6 One study of resistancefound that children who received antibiotics formore than 4 weeks in the previous 6 months weremore likely to have resistant Escherichia coliisolates than children who had not received pro-longed antibiotic treatment (odds ratio [OR]=13.9;95% CI, 8.2–23.5). Children with abnormalities of the genitourinary tract were approximately 4 times more likely to have resistant isolates of E coli than children without abnormalities of thegenitourinary tract (OR=3.9; 95% CI, 2.7–5.7).11■ RECOMMENDATIONS FROM OTHERSThe American Academy of Pediatrics, AmericanUrological Association, and the Swedish MedicalResearch Council guidelines recommend prophy-laxis for children with reflux (Table), but they allacknowledge that the recommendations are notsupported by well-designed randomized con-trolled trials.1–3 No guidelines are available forchildren with neurogenic bladder and recurrenturinary tract infections.7Amer Shakil, MD, Lane Reed, MD, Department ofFamily Practice and Community Medicine, University of TexasSouthwestern, Dallas; Laura Wilder, MLS, University ofTexas Southwestern Medical Center Library, Dallas(RR=0.79; 95% CI, 0.61–1.02). There weremany problems with the methodological qualityof these trials, including significant heterogene-ity. The researchers concluded that well-designed randomized controlled trails are stillneeded to evaluate this commonly used inter-vention in the pediatric population.4 Benefits for long-term prophylaxis are even less clear in children with low-grade reflux (I–II).5Furthermore, no randomized controlled trialsassess whether prophylaxis prevents the devel-opment of new renal scars in children.6In addition, a recent systematic review of stud-ies done in children with normal urinary tracts, aswell in children with neurogenic bladders, foundthat the available evidence is of low quality. Only6 out of 31 potential studies fulfilled the inclusioncriteria. These were small (mean sample size was28), and the quality scores of all 6 trials were low,indicating that the evidence may be unreliable.7Two of 3 studies done in children with normalurinary tracts demonstrated statistically signifi-cant higher rates of UTI recurrence in controlgroups compared with treatment groups receiv-ing 6 to 10 months of either nitrofurantoin or cot-rimoxazole (RR=24–31). The third study showedno difference between groups. One of 2 trials in children with neurogenic blad-der demonstrated higher recurrence rates of 2.9per 10 patient years for patients receiving antibi-otics compared with 1.5 in the untreated group.The other study showed lower recurrence rates of17.1 for patients receiving antibiotics, comparedwith 33 in the untreated group.7 Neither of thesefindings were statistically significant. A different meta-analysis of 15 controlled clin-ical trials in children with neurogenic bladder dueto spinal cord dysfunction. This analysis showedthat antibiotic prophylaxis was associated with areduction in asymptomatic bacteruria among chil-dren with acute spinal cord injury (P<.05), butthere was no significant reduction in sympto-matic infections. Prophylaxis resulted in anapproximately twofold increase in antimicrobial-resistant bacteria. The researchers concluded thatNo controlled prospective studiesexamine the effectiveness of antibiotics to prevent UTIC L I N I C A L  I N Q U I R I E S500 JUNE 2004 / VOL 53, NO 6 · The Journal of Family Practice■ CLINICAL COMMENTARY:UTI prevention most successful whenthe child exhibits efficiency of voidingThe relative benefit of antibiotic prophylaxis inprevention of UTI in children with anatomicabnormalities like vesicoureteral reflux couldbest be determined if all other risk factors forUTI were controlled. Unfortunately, these otherfactors are often more significant in promotingUTI than is reflux, and they are also more diffi-cult to quantify. Voiding dysfunction and con-stipation can both increase bladder storagepressures and postvoid residual urine volumes,and as such greatly predispose children forUTI. Furthermore, a distended colon providesan abundant reservoir of pathogens with anarray of uropathogenic virulence factors.Published reports have failed to detect signif-icant benefit for antibiotic prophylaxis in partbecause the children studied possess varyingrisks for UTI. Prevention of UTI is most suc-cessful when the child exhibits efficiency ofvoiding and elimination. Clinical practice inpediatric urology advocates use of antibioticprophylaxis in children with vesicoureteralreflux. Reflux should be suspected in childrenwith hydroureter, multicystic renal dysplasia,ureteral duplication, and ureterocele.William R. Strand, MD, Division of Pediatric Urology,University of Texas Southwestern Medical Center, DallasOral antibiotics for prophylaxis of urinary tract infections in children Antimicrobial Prophylaxis dosageTrimethoprim/sulfamethoxazole 2 mg of TMP, 10 mg of SMX per kg as single bedtime or(TMP/SMX) (Bactrim, Septra) 5 mg of TMP, 25 mg of SMX per kg twice per weekNitrofurantoin (Macrodantin) 1–2 mg/kg as single daily doseCephalexin (Keflex) 10 mg/kg as single daily doseAmoxicillin 10 mg/kg as single daily doseSulfisoxazole (Gantrisin Pedatric) 10–20 mg/kg divided every 12 hModified with permission from AAP 1999;3 Allen et al1999.10TA B L EREFERENCES1. Jodal U, Lindberg U. Guidelines for management of childrenwith urinary tract infection and vesico-ureteric reflux.Recommendations from a Swedish state-of-the-art confer-ence. Swedish Medical Research Council. Acta Paediatr Suppl1999; 88:87–89.2. Elder JS, Peters CA, Arant BS Jr, et al. PediatricVesicoureteral Reflux Guidelines Panel summary report onthe management of primary vesicoureteral reflux in children.J Urol 1997; 157:1846–1851.3. Practice parameter: the diagnosis, treatment, and evaluationof the initial urinary tract infection in febrile infants andyoung children. American Academy of Pediatrics. Committeeon Quality Improvement. Subcommittee on Urinary TractInfection. Pediatrics 1999; 103:843–852.4. Hoberman A, Charron M, Hickey RW, Baskin M, Kearney DH,Wald ER. Imaging studies after a first febrile urinary tractinfection in young children. N Engl J Med 2003; 348:195–202.5. Williams G, Lee A, Craig J. Antibiotics for the prevention ofurinary tract infection in children. A systematic review of ran-domized controlled trials. J Pediatr 2001; 138:868–874.6. Bollgren I. Antibacterial prophylaxis in children with urinarytract infection. Acta Paediatr Suppl 1999; 88:48–52.7. Le Saux N, Pham B, Moher D. Evaluating the benefits ofantimicrobial prophylaxis to prevent urinary tract infectionsin children: a systematic review. CMAJ 2000; 163:523–529.8. Morton SC, Shekelle PG, Adams JL, et al. Antimicrobial pro-phylaxis for urinary tract infection in persons with spinal corddysfunction. Arch Phys Med Rehabil 2002; 83:129–138.9. Ghiro L, Cracco AT, Sartor M, Comacchio S, Zacchello G,Dall’Amico R; Veneto Urinary Tract Infection Study Group.Retrospective study of children with acute pyelonephritis.Evaluation of bacterial etiology, antimicrobial susceptibility,drug management and imaging studies. Nephron 2002; 90:8–15.10. Evidence based clinical guideline for children with firstUTI, Health Policy and Clinical Effectiveness Program.Cincinnati, Ohio: Cincinnati Children’s Hospital MedicalCenter; 1999. Available at: www.cincinnatichildrens.org/svc/dept-div/health-policy/ev-based/uti.htm. Accessed onMay 5, 2004.11. Allen UD, MacDonald N, Fiute L, Chan F, Stephen D. Riskfactors for resistance to “first-line” antimicrobials amongurinary tract isolates of Escherichia coli in children.CMAJ 1999; 160:1436–1440.

Do antibiotics prevent recurrent UTI in children with anatomic abnormalities?

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