ORLANDO – Antibiotic prophylaxis was shown in the recently published RIVUR trial to halve the risk of recurrent febrile urinary tract infection in infants and young children with vesicoureteral reflux. Conversely, a meta-analysis of six controlled trials concluded there is little to no benefit of antibiotic prophylaxis in this population.
The conflicting data highlight the ongoing debate regarding the best approach for preventing and managing febrile urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR).
The RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial findings, which were published in May in the New England Journal of Medicine, showed that among children with VUR who were aged 2-71 months, 2 years of treatment with trimethoprim-sulfamethoxazole halved the risk of febrile or symptomatic UTI recurrence (N. Eng. J. Med. 2014;370:2367-76). The difference between those who received prophylaxis and those who did not emerged early and increased over the 2-year study period, Dr. Saul Greenfield said during an update on the trial results at the annual meeting of the American Urological Association.
"The magnitude of treatment effect warrants serious consideration of prophylaxis in these children. We also feel that these results warrant reconsideration of the recent guideline recommendations by the American Academy of Pediatrics in 2011 ... advising against evaluation of children with a VCUG [voiding cystourethrogram] after their first UTI," said Dr. Greenfield, director of pediatric urology at Women and Children’s Hospital of Buffalo, N.Y. and one of the RIVUR investigators.
That AAP recommendation was based on a number of studies that showed no benefit from antibiotic prophylaxis in children with VUR, which suggests there is little value in diagnosing VUR (Pediatrics 2011;28:595-610).
In fact, a meta-analysis of six controlled trials, which also was presented at the AUA meeting, suggested that the benefit of antibiotic prophylaxis for preventing febrile UTIs in children with VUR is small at best, and evidence to support its use is lacking.
Pooled data for 986 patients included in the trials showed that in 417 with dilating VUR, the risk of recurrent febrile UTI was 22.46% in those who received antibiotics, and 29.79% in controls. The relative risk of treatment failure with antibiotic prophylaxis was 0.75, and the absolute risk reduction was 7.33%, Dr. José Netto reported.
The number needed to treat to prevent one UTI was 13.64, according to Dr. Netto of State University of Feira de Santana in Brazil.
In 515 patients with nondilating VUR, the risk of febrile UTI was 5.31% in patients who received prophylactic antibiotics, and 6.09% in those who did not. The relative risk of treatment failure was 0.87, and the absolute risk reduction was 0.78%. The number needed to treat was 129, Dr. Netto said.
The studies included in the meta-analysis were published prior to August 2013. Only one was placebo-controlled. Patients included in the study included 663 girls (67.2%), and the median age of all patients was 21 months.
The studies all used co-trimoxazole in standard doses, and three of the six also used co-amoxiclav or nitrofurantoin as alternative treatments.
Antibiotic prophylaxis is often used in children with VUR, but several recent studies have failed to demonstrate the usefulness of this approach with respect to reducing the risk of febrile UTI, Dr. Netto said, noting that the studies included heterogeneous populations with distinct grades of VUR and varying rates of recurrent UTI.
Based on the current findings, it remains uncertain whether antibiotic prophylaxis reduces the risk of febrile UTI in children with VUR, although it is possible – given the differences seen between those with dilating VUR and those with nondilating VUR – that specific subgroups of children with dilating VUR may benefit from prophylaxis, he concluded.
The conflicting findings between this meta-analysis, and the RIVUR trial underscore the importance of ongoing evaluation of antibiotic prophylaxis.
"The best ways to prevent and treat febrile urinary tract infections in children with VUR are still very much up for discussion," Dr. Anthony Atala, W.H. Boyce Professor and chair of the urology department at Wake Forest Baptist Medical Center in Winston-Salem, N.C., said in an AUA press statement.
"Examining and reexamining the AAP guidelines and practices that guide our work are critical to better understand the condition and improve the lives of those children who are living with the condition each day," said Dr. Atala, who is also director of the Wake Forest Institute for Regenerative Medicine.
Dr. Atala reported serving in a leadership position at Plureon Corp. Dr. Greenfield and Dr. Netto reported having no disclosures.