prophylactic antibiotics in kids with UTI and vesicoureteral reflux

Vesicoureteral reflux is common in kids, is present in the third of children with febrile UTIs, and is associated with increased risk of renal scarring.  Studies have found mixed results on the efficacy of prophylactic antibiotics.  New England Journal with recent article -- a two-year randomized control trial in 607 children with vesicoureteral reflux diagnosed after a first or second febrile or symptomatic UTI, randomized to trimethoprim-sulfamethoxazole prophylaxis (3 mg trimethoprim, 15 mg sulfamethoxazole per kg of body weight) or placebo.  Primary outcome was preventing recurrent infections.  Secondary outcome was assessment of renal scarring, treatment failure (a composite of recurrences and scarring) and antimicrobial resistance (see vesicoureteral reflux abx in kids nejm 2014 in dropbox, or DOI: 10.1056/NEJMoa1401811).  All urines were collected by catheterization or suprapubic aspiration.  Renal scanning was done at baseline and after 1 and 2 years.  Results:

            --Average age 12 mo, 92% girls, 80% white, 40% with grade 2 and 40% with grade 3 reflux, 96% without any renal scarring at baseline

--Recurrent UTI in 39 of 302 children on prophylaxis versus 72 with 305 children on placebo (HR 0.50; CI 0.34-0.74).  8 children would need to be treated for 2 years to prevent one case of febrile or symptomatic UTI.

            --In children whose index infection was febrile, prophylaxis even more effective (HR 0.41; CI 0.26-0.64)

            --children with grade 3 or 4 reflux at baseline were at higher risk, with 22.9% versus 14.3% having a febrile or symptomatic recurrence

            --Renal scarring did not differ between groups (11.9% with medication versus 10.2% with placebo)

            --Voiding cystourethrography was performed at 2 years, was resolved in 51%, improved in 23%, unchanged in 18.5%, and worse in 7.2%.

--In 87 children with a first recurrence caused by Escherichia coli, proportion of isolates resistant to trimethoprim-sulfamethoxazole was 63% of prophylaxis group, and 19% in the placebo group

so, what does this all mean?   On the one hand, there clearly was benefit of prophylaxis to prevent symptomatic recurrence, and recurrent UTI could result in kids getting very sick quickly and needing to be hospitalized.  On the other hand, the fact that there was no significant increase in renal scarring without antibiotics is reassuring and the increase in antimicrobial resistance is concerning.  Some concerns with the study include the fact that only one antibiotic was used, and the fact that renal scarring was only assessed after 2 years, though the potential for renal scarring may extend beyond that time.  One option (from my secondary analysis of the data) might be to risk stratify patients: use prophylaxis if their first event was a febrile UTI and they have grade 3 or 4 reflux, or patients with multiple recurrent UTIs, or those with bladder or bowel dysfunction (who had a higher rate of recurrence in above study).  Another option, also not explored, is to give parents a prescription for full course antibiotics at home, with instructions to call the on-call primary care physician as soon as a child gets sick (allowing the option for very early treatment of an incipient infection).