A Shift in the Antibiotic Prophylaxis Debate?

The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trialwas supposed to provide clear direction for pediatric urologists. To date, it is the largest double-blind, placebo-controlled, randomized, multicenter study examining urinary tract infection and renal scarring in children with vesicoureteral reflux (VUR). Despite the study’s strong design and sample size of more than 600 children, its results and recommendations continue to be met with resistance.

“If you go back a decade or so, we used to prescribe prophylaxis routinely in most children with vesicoureteral reflux,” says Tej K. Mattoo, MD, a principal investigator on the RIVUR trial and chief of Pediatric Nephrology and Hypertension at Children’s Hospital of Michigan, Detroit Medical Center. “Then a series of studies and guidelines — based on lower quality evidence — were released and people felt we should not use routine prophylaxis. It’s not surprising there is disagreement on the topic.”

Next came the RIVUR trial’s results, published in 2014 in the New England Journal of Medicine. The study revealed antibiotic prophylaxis cut UTI recurrence nearly in half compared to children taking a placebo. A flurry of critical commentaries followed, which the trial’s investigators addressed in a rebuttal in the journal Pediatric Nephrology.

“Not using prophylaxis for anyone is not an option. Selective prophylaxis is what we need to do,” says Dr. Mattoo, lead author of the group’s editorial response. “We as clinicians need to figure out which patients are going to benefit from prophylaxis.”

According to Dr. Mattoo, factors including severity of the reflux, patient gender, family history of VUR, recurrence of UTI, kidney damage and parental opinion should be weighed by the clinician in the case of older children with VUR. But he defends the group’s recommendation for prophylaxis in young children.

“I wouldn’t take the chance of forgoing prophylaxis with children who aren’t yet toilet trained,” Dr. Mattoo says. “The risk of infection is higher, symptoms are not as straightforward, collecting urine samples is not easy, sepsis and need for intravenous antibiotics are more likely, and the list goes on.”

He concedes that the idea of a point-of-care decision may not lend itself to clear clinical guidelines favored by groups such as the American Academy of Pediatrics. But Dr. Mattoo believes that current and future research efforts will inform clinicians in their treatment decisions by identifying patients at the highest risk of recurrent infections or scarring. In the meantime, he prefers to err on the side of prophylactic treatment in high-risk children.

“When I’m talking to parents, what matters is what will happen to that particular child, not what happens to others,” Dr. Mattoo explains. “If you can lower the risk of infection for that particular patient, it’s worth it.”

Join the conversation. Would guidelines resolve the controversy, or will the idea of prophylactic antibiotics always ruffle feathers?

References

1. Mattoo TK, Carpenter MA, Moxey-Mims M, Chesney RW; For The RIVUR Trial Investigators. The RIVUR trial: a factual interpretation of our data.Pediatric Nephrology. 2015 Jan 6. [Epub ahead of print]

2. RIVUR Trial Investigators, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. New England Journal of Medicine. 2014 Jun 19, 370(25):2367-76.