Continuous Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux

In this multicentric, open label, randomized trial performed across 39 European centers, the investigators randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux (VUR) and no previous episode of urinary tract infection (UTI) to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V VUR. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group [hazard ratio 0.55; 95% confidence interval (CI) 0.35 to 0.86; P = 0.008]; the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. Pseudomonas species, other non–Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. The investigators concluded that in infants with grade III, IV, or V VUR and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non–E.coli organisms and antibiotic resistance.