Preventing Pyelonephritis and Renal Scars ? A Randomized , Controlled Trial Is Antibiotic Prophylaxis in Children With Vesicoureteral Reflux Effective in

OBJECTIVES. There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux. METHODS.One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans. RESULTS. The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis. CONCLUSIONS.Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV. Pediatrics 2008;121:e1489–e1494 I RECENT YEARS, the effectiveness of continuous antibiotic prophylaxis in children with vesicoureteral reflux (VUR) has been intensely discussed.1–7 The question is not only whether antibiotics are effective in preventing recurrent acute pyelonephritis but also whether they modify the natural history of disease and help to prevent the appearance of new kidneys scars. The evidence on the effectiveness of antibiotic prophylaxis on both outcomes is scanty: the randomized, controlled trials (RCTs) published so far are poorly designed and conducted in very heterogeneous populations of children (ie, spanning from 6 months to 14–18 years of age and pooling patients with and without VUR).5 A recently updated Cochrane Systematic Review confirmed heterogeneity and poor quality of studies on this topic. The authors suggested that high-quality RCTs are needed to determine the effectiveness of long-term antibiotics for the prevention of urinary tract infections (UTI) in susceptible children.3 Moreover, the presence of VUR has not been firmly shown to be a risk factor for recurrence of pyelonephritis, and a direct association between VUR and the presence of scars or the appearance of new scars has not been demonstrated. The only available evidence is www.pediatrics.org/cgi/doi/10.1542/ peds.2007-2652 doi:10.1542/peds.2007-2652 This trial has been registered at www.clinicaltrials.gov (identifier NCT00382343).