A study led by researchers at Children's Hospital of Pittsburgh of UPMC demonstrated that children diagnosed with an abnormal flow of urine from the bladder to the upper urinary tract, called vesicoureteral reflux (VUR), can avoid recurrent urinary tract infections (UTI) by taking daily low-dose antibiotics, although the treatment didn't reduce their risk for UTI-induced kidney scarring. The results of the multi-center study will be presented at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada. The study also is published in the New England Journal of Medicine.
"Our study provides a clear message that recurrences of UTI in children with vesicoureteral reflux can be prevented, some of these children appear pretty sick when they have a UTI with fever," said Alejandro Hoberman, M.D., chief, Division of General Academic Pediatrics at Children's Hospital of Pittsburgh. "VUR is present in one-third of children presenting with UTI accompanied by a fever and has been associated with a heightened risk of kidney scarring. One way to decrease infection risk is to give children antibiotics when they are well, called antimicrobial prophylaxis."
Earlier randomized, controlled trials that compared anti-reflux surgery with antimicrobial prophylaxis showed no differences in rates of recurrent UTIs and renal scarring; however, the actual efficacy of either treatment could not be determined because the studies lacked a placebo or observation comparison groups. Recently conducted randomized trials have reported conflicting results about the effectiveness of antimicrobial prophylaxis in reducing recurrences.
"This study showed unequivocal evidence that antimicrobial prophylaxis reduced at least in half the likelihood of children having recurrent UTIs," said Dr. Hoberman, also professor of pediatrics at the University of Pittsburgh School of Medicine. "Some subgroups of children derived the most benefit, particularly those with bladder and bowel dysfunction at baseline, and those in whom the UTI occurred with fever."
The goal of the two-year study was to determine if giving children low-dose trimethoprim-sulfamethoxazole would prevent recurrent UTIs, decrease kidney scarring and contribute to the emergence of bacterial resistance.
The study, named the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial, enrolled 607 children ages 2 to 71 months who were diagnosed with VUR following a first or second episode of UTI. Participants were recruited from 19 clinical trial centers in the United States and underwent kidney scans to determine if scarring was present. They were then randomized to receive trimethoprim-sulfamethoxazole or a placebo. Kidney scans were repeated at one and two years after study entry.
Results showed that 39 of 302 children (13 percent) receiving antimicrobial prophylaxis developed UTIs compared to 72 of 305 (24 percent) receiving placebo. Antimicrobial prophylaxis reduced the risk of infections by 50 percent compared with placebo.
"Rates of renal scarring at the outcome visit were low and not reduced by prophylaxis, perhaps because most children were enrolled after their first infection and because parents, instructed to be vigilant, sought early medical attention," said Dr. Hoberman. "Not unexpectedly, recurrences that did occur in children who received prophylaxis were more likely to have been caused by a resistant pathogen."
This research was supported by grants U01 DK074059, U01 DK074053, U01 DK074082, U01 DK074064, U01 DK074062, U01 DK074063 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services. This trial also was supported by the University of Pittsburgh Clinical and Translational Science Award (UL1RR024153 and UL1TR000005) and the Children's Hospital of Philadelphia Clinical and Translational Science Award (UL1TR000003) both from the National Center for Research Resources, now at the National Center for Advancing Translational Sciences, National Institutes of Health.