Prophylactic Antimicrobials Linked to Recurrent UTIs in Children?
Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R.
JAMA. 2007;298:179-186.

The authors note that many of the studies about risk of recurrent urinary tract infection (UTI) in children come from evaluated referral populations, not children from community practices.

The current recommendation is that certain children with first UTIs undergo an imaging study to evaluate for vesicoureteral reflux (VUR), and those with higher grades should receive prophylactic antibiotics. The authors note that these recommendations are supported by limited data, and this study sought to fill in important gaps about expected rates of recurrent UTIs and the role of prophylactic antibiotics.

This study evaluated 5 years of data from a 3-state primary care research network in the Northeast. Using a common electronic medical record, and hard copy review when needed, the authors identified 611 children with a first UTI and 83 (13.6%) with a recurrent UTI during the study period from a total patient population of > 74,000 children.

A recurrent UTI was one that occurred at least 2 weeks after the initial one, and all culture specimens were obtained by catheterization or clean catch. Sixty-one percent of the recurrent UTIs consisted of an isolate resistant to at least 1 antibiotic.

The sample was 89% female and 57% white, and only 34.5% underwent a VUR study after the initial UTI. Children older than 2 years of age had VUR studies only 20% of time. Twenty-one percent had been placed on prophylactic antibiotics. In multivariable analyses, controlling for gender, race, age, results of VUR imaging, and exposure to prophylactic antibiotics, the following factors were associated with an INCREASED risk (hazard ratio, HR) of recurrent UTI: white race (HR 1.97), grade 4 or 5 VUR (HR 4.38), and age 3-5 years old (relative to children younger than 1 year of age).

The HR for prophylaxis was 1.01, suggesting an equal hazard of a recurrent UTI (95% CI 0.50-2.02) for children on prophylaxis relative to those not on prophylaxis. However, exposure to prophylaxis greatly increased the risk of having a resistant isolate for the recurrent episode (HR 7.50, 95% CI 1.60-35.17).

Three patients with grade 4 or 5 VUR had recurrent UTIs, and all 3 had a resistant isolate. The rate of initial UTI in this cohort was 4.2% for all children (cumulative incidence) between 0 and 6 years old. The rate of recurrent UTI among those with a first UTI was 12% per year.

The authors conclude that antimicrobial prophylaxis is not associated with decreased risk for recurrent UTI and instead raises the risk of a resistant organism among children who experience a recurrent UTI.

The authors note that one of the limitations of this study is the fact that only 7 patients in the cohort had grade 4 or 5 vesicoureteral reflux, so one must be careful about too quickly assuming no role for prophylactic antibiotics. What these data and other recent studies emphasize is the real need for better data to answer the questions around the role of prophylaxis. Given the stakes involved (renal scarring or injury?), it's not surprising that there is a dearth of randomized prophylaxis data on children with grade 4 or 5 vesicoureteral reflux, but I wonder if the building momentum of recent studies might not be moving toward just such a multicenter trial. The authors suggest that we might want to consider discussing the un-established pros of prophylaxis (reduced risk of renal injury) with the real risk found in this study (increased rates of resistant organisms), and we may be nearing a point where that discussion with parents might be appropriate.

Abstract