Treatment shown to reduce recurrent urinary tract infections in high-risk children
May 5, 2014
One third of all children affected with febrile urinary tract infections suffer from vesicoureteral reflux, a condition in which the urine flows backward into the kidneys from the bladder. A new study, co-authored by a researcher from The University of North Carolina’s Gillings School of Global Public Health, found that children with vesicoureteral reflux receiving antimicrobials over a two-year period (antimicrobial prophylaxis) had a substantially reduced risk of urinary tract infection recurrences compared with children receiving a placebo.
The study, titled “Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux” was published online in The New England Journal of Medicine on May 4. Myra Carpenter, PhD, senior investigator, Biostatistics, was a co-author and co-principal investigator.
Carpenter and members of Biostatistics’ Collaborative Studies Coordinating Center (CSCC) were instrumental in trial design, data management, quality control, oversight for blinded outcome (UTI) classification and statistical analysis.
Normally, urine flows only downward from the kidneys to the bladder. Vesicoureteral reflux (VUR) is the abnormal flow of urine from the bladder back up the tubes that connect the kidneys to the bladder. VUR is present in one-third of children presenting with urinary tract infection (UTI) accompanied by a fever and has been associated with a heightened risk of kidney scarring.
Earlier randomized, controlled trials that compared anti-reflux surgery with antimicrobial prophylaxis showed no differences in rates of recurrent urinary tract infection and renal scarring; however, lack of a placebo or observation group precluded a determination that either surgery or prophylaxis was effective. Recently conducted randomized trials, most unblinded, have reported conflicting results about the effectiveness of antimicrobial prophylaxis in reducing recurrences.
The aim of this double-blind trial 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. Called the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial, the study enrolled 607 children ages 2 months to 71 months who were diagnosed with VUR following a first or second episode of UTI.
Participants were recruited from 19 clinical centers in the United States and underwent kidney scans to determine whether scarring was present at baseline. Children were randomized to receive trimethoprim-sulfamethoxazole or a placebo; kidney scans were repeated at one and two years.
Results showed that 39 of 302 children (13 percent; percent is estimated taking into account patients who did not complete 24 months follow-up) receiving antimicrobial prophylaxis developed UTIs after 24 months compared to 72 of 305 (25 percent) receiving a placebo. Antimicrobial prophylaxis reduced the risk of infections by 50 percent compared with a placebo. Although there were fewer UTIs with prophylaxis, the likelihood of the infection being resistant to trimethoprim-sulfamethoxazole was increased.
Prophylaxis was most effective in children who had a fever with their initial UTI and in those with bladder and bowel dysfunction at baseline. The occurrence of kidney scarring did not differ between the two groups (12 percent for the treatment group vs. 10 percent for the placebo group).
“I am proud to have been part of this landmark trial evaluating the efficacy of antimicrobial prophylaxis to reduce the recurrence of UTIs in children with VUR,” Carpenter said. “Through working with a dedicated team at UNC and the participating clinical sites, we definitively answered our primary question—daily prophylaxis with trimethoprim-sulfamethoxazole greatly reduced the risk of recurrent UTI. The results provide pediatricians, pediatric urologists and pediatric nephrologists with the evidence they need to better treat infants and children with vesicoureteral reflux who have had a urinary tract infection. It also will give parents of children with VUR much-needed information as they consider treatment options.”
Carpenter credited her co-authors as well as the expansive UNC team working on the study coordination.
That team included Anastasia Ivanova, PhD, associate professor of biostatistics, principal investigator for the CSCC; Lisa Gravens-Mueller, MS, biostatistician, supervisor, biostatistics; and Hope Bryan, MS, IT manager, biostatistics, of the Gillings School; and UNC School of Medicine faculty William Primack, MD, clinical professor of medicine; Richard Sutherland, MD, clinical associate professor of urology; and Timothy Bukowski, MD, clinical associate professor of urology, who reviewed clinical data and determined which cases met stringent standardized criteria for urinary tract infection.
Sonia Davis, DrPH, Professor of the Practice, Department of Biostatistics, and CSCC director, had high praise for the research team.
“The study relied heavily on our faculty and staff’s extraordinary expertise in the design, implementation and analysis of collaborative large-scale multi-center double-blind clinical trials, continuing the CSCC’s more than 40-year history at the forefront of public health research projects,” Davis said.
The study also was presented May 4 at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada.
Copy provided by AAP was included in this story.