Drug combo reduces UTIs in kids by up to 80%

Dr Hoberman

Long-term use of a combination antimicrobial trimethoprim sulfamethoxazole (TMP/SMZ) reduces the risk of recurrent urinary tract infection (UTI) by up to 80% in children with the urinary condition vesicoureteral reflux compared to placebo, according to a study published online May 4 in the New England Journal of Medicine.

The research was funded by the National Institutes of Health (NIH).

The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) was a multisite, double-blind, placebo-controlled randomized clinical trial of 607 children between aged 2 and 71 months diagnosed with grade 1 – 4 VUR after their first or second UTI. Children underwent evaluation for scarring by DMSA scanning at study entry, then 1 and 2 years after. They were also evaluated for evidence of developing antimicrobial resistance.

Two years of prophylactic treatment with TMP/SMZ for children with vesicoureteral reflux diagnosed after a UTI was effective in reducing the risk of recurrent UTI by 50% to 80%, according to the study.

"Our study provided unequivocal evidence that antimicrobial prophylaxis reduced at least in half the likelihood of children having recurrent febrile or symptomatic UTIs. 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," said lead author Alejandro Hoberman, MD, chief, division of general academic pediatrics at Children's Hospital of Pittsburgh.

“The highest risk reduction was seen in children with bladder and bowel dysfunction,” Marva

Dr Moxey-MimsMoxey-Mims, MD, pediatric nephrologist (kidney specialist) and deputy director for clinical science for the Division of Kidney, Urologic, and Hematologic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, a component of NIH.

“There was not a significant difference in the amount of renal scarring rates between the 2 groups at study exit, which was unexpected, although the follow-up time was relatively short for this outcome,” Dr Moxey-Mims said. “The scarring rates were low to start with, and parents were very vigilant about seeking early treatment for any signs of UTI.”

According to Moxey-Mims, the results of the RIVUR study are pertinent to formulary managers “in terms of ensuring that their formularies include antimicrobials that can be used for UTI prophylaxis in children with VUR,” she said.

“In children receiving prophylactic antimicrobials, there was a significant reduction in the recurrence of UTI,” she said. “The risk reduction was highest in the children who had a febrile UTI and those who had bladder and bowel dysfunction. Physicians and parents should carefully weigh the evidence and factors that influence their decision with regard to prophylaxis.”

Other studies may seek to determine whether other antimicrobials show a similar or greater benefit, further analyses of resistance patterns, and perhaps longer follow-up to see whether the scarring rates change over the long-term and impact kidney function, she added.