Children with first urinary tract infection may not benefit from antibiotic prophylaxis

Article Outline

• Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298:179-86
  • Question
  • Design
  • Setting
  • Participants
  • Outcomes
  • Main Results
  • Conclusions
  • Commentary
• References
• Copyright

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Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298:179-86 

Question 

Among children with a first urinary tract infection (UTI), what risk factors predict recurrent UTI, is there an association between antimicrobial prophylaxis and recurrent UTI, and what risk factors predict antimicrobial resistance in recurrent UTIs?

Design 

Cohort study, with a nested case-control study for children diagnosed with recurrent UTI.

Setting 

Twenty-seven primary care pediatric practices in urban, suburban, and semi-rural areas spanning 3 states.

Participants 

From a primary care cohort of children aged ≤6 years (n = 74,974), 611 children diagnosed with a first UTI were identified; 83 of these children had recurrent UTI during the study period.

Outcomes 

Time to recurrent UTI and antimicrobial resistance of recurrent UTI pathogens.

Main Results 

Of the children in the network, 611 (0.007 per person-year) had a first UTI, and 83 (0.12 per person-year after first UTI) had a recurrent UTI. In multivariable Cox time-to-event models, factors associated with increased risk of recurrent UTI included white race (0.17 per person-year; hazard ratio [HR], 1.97; 95% CI, 1.22-3.16), age 3 to 4 years (0.22 per person-year; HR, 2.75; 95% CI, 1.37-5.51), age 4 to 5 years (0.19 per person-year; HR, 2.47; 95% CI, 1.19-5.12), and grade 4 to 5 vesicoureteral reflux (0.6 per person-year; HR, 4.38; 95% CI, 1.26-15.29). Sex and grade 1 to 3 vesicoureteral reflux were not associated with risk of recurrence. Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI (HR, 1.01; 95% CI, 0.5-2.02), even after adjusting for propensity to receive prophylaxis, but was a risk factor for antimicrobial resistance in children with recurrent UTI (HR, 7.5; 95% CI, 1.6-35.17).

Conclusions 

In the children in this study, antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections.

Commentary 

This study adds to a growing body of literature that challenges the need for prophylactic antibiotics and voiding cystourethrograms (VCUGs) in children who have sustained their first UTI, an approach felt to reduce the rate of recurrent infections, especially in children with associated vesicoureteral reflux (VUR), who may be at risk for development of reflux nephropathy. Using an electronic medical record covering numerous primary care practices affiliated with the Children’s Hospital of Philadelphia, the investigators demonstrated that prophylactic antibiotics not only did not reduce the rate of recurrent infections, they increased the risk of the development of a resistant organism. Additionally, the risk of recurrent infections did not seem to increase in the presence of reflux, especially for grades 1 to 3 VUR. So should we throw out the prescription pad and stop ordering studies to detect VUR? Not so fast. As the authors state, the rate of performance of VCUGs was relatively low in the children included in the study, despite many recommendations to the contrary. There were also very few children with higher grades of reflux, and no analysis of renal scarring/reflux nephropathy was conducted. Therefore, this study does not provide sufficient rationale to stop performing VCUGs. Furthermore, although detailed prescribing data were available to the investigators, resistance patterns were not analyzed on the basis of the antibiotic prescribed. This is important because certain antibiotics, specifically amoxicillin and the cephalosporins, are incompletely absorbed in the upper gastrointestinal tract and therefore do get into the colon, where they can cause the gut flora to become resistant. Nitrofurantoin and trimethoprim/sulfamethoxazole, however, are better absorbed, so relatively little of them get into the colon, thereby reducing the likelihood of increased antibiotic resistance.¹ If the practices in the Children’s Hospital of Philadelphia network were in a habit of using amoxicillin or cephalosporins for prophylaxis, this could explain the increased risk of antibiotic resistance. Finally, and perhaps most importantly, these data highlight the need for a properly conducted, randomized controlled trial of antimicrobial prophylaxis in the prevention of recurrent UTIs and renal scarring. The National Institutes of Diabetes and Digestive and Kidney Diseases is currently sponsoring such a trial, the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) trial (Clinical trials.gov #NCT00405704).² Until the results of RIVUR are available, practitioners should have thoughtful discussions with patients’ families before prescribing prophylaxis, at least in those children without known high-grade VUR. When prophylaxis is prescribed, it is probably wise to only prescribe those antibiotics that have the lowest likelihood of inducing resistance.¹

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References 

1. Wald ER. Vesicoureteral reflux: the role of antibiotic prophylaxis. Pediatrics. 2006;117:919–922
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2. Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR). Available at: http://www.cscc.unc.edu/rivur/. Accessed Jul 24, 2007.
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