Antibiotic Prophylaxis and Recurrent Urinary Tract Infection in Children

TLDR

Antibiotics are widely used to prevent urinary tract infection in children, yet placebo‑controlled trials proving efficacy are lacking. This multicenter trial evaluated whether low‑dose, continuous oral trimethoprim‑sulfamethoxazole prevents recurrent urinary tract infection in children predisposed to the disease. Children under 18 with prior microbiologically confirmed urinary tract infections were randomized to daily trimethoprim‑sulfamethoxazole or placebo for 12 months, with the primary outcome being microbiologically confirmed symptomatic urinary tract infection; analyses used intention‑to‑treat time‑to‑event data on 576 participants (median age 14 months, 64 % girls). The antibiotic group experienced a 13 % incidence of urinary tract infection versus 19 % in placebo, yielding a hazard ratio of 0.61 (95 % CI 0.40–0.93, P = 0.02), a 6‑percentage‑point absolute risk reduction consistent across subgroups. Trial registered at ACTRN12608000470392.

Abstract

Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions).Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)