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Prophylactic antibiotics prevented UTI recurrences in children with VUR
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VANCOUVER, British Columbia — Children diagnosed with vesicoureteral reflux after a first or second urinary tract infection had their risk of recurrence reduced by 50% if treated prophylactically with antimicrobials, according to late-breaker data presented here by lead author of the study Alejandro Hoberman, MD, FAAP.
Hoberman, an Infectious Diseases in Children Editorial Board member and the 2014 recipient of the Academic Pediatric Association’s Research Award, and colleagues conducted the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial to determine if a low-dose of trimethoprim/sulfamethoxazole (TMP/SMX) given to children for 2 years would prevent recurrent UTIs, decrease kidney scarring and contribute to the emergence of bacterial resistance.
Alejandro Hoberman
The study was also published in the New England Journal of Medicine on May 4.
The trial enrolled 607 children aged 2 to 71 months who were diagnosed with VUR following a first or second episode of UTI.
“This was the first UTI for more than 90% of children and the UTI was febrile in 85% of cases,” Hoberman said during his presentation.
Participants were recruited from 2007 to 2011 from 19 US clinical trial centers and underwent kidney scans to determine if scarring was present at baseline. The patients were then randomized to receive TMP/SMX or a placebo; kidney scans were repeated at 1 and 2 years. Follow-up was completed in June 2013.
Results showed that 39 of 302 children (13%) who received antimicrobial prophylaxis developed UTIs compared with 72 of 305 (25%) children who received placebo.
“These differences were apparently early on and widened progressively over time,” Hoberman said. “Overall, we found a 50% reduction in the proportion of children with febrile or symptomatic UTI recurrences, with a very tight confidence interval.”
Hoberman said children whose index infection was febrile and children with bladder and bowel dysfunction at baseline derived the most benefit from prophylaxis, with reductions in recurrences of 60% to 80%, respectively.
The occurrence of kidney scarring did not differ between the two groups (12% for the treatment group vs. 10% for the placebo group).
“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 Hoberman, chief of the Division of General Academic Pediatrics at Children’s Hospital of Pittsburgh and professor of pediatrics at University of Pittsburgh School of Medicine.
He added that the fewer recurrences among those who received prophylaxis were more likely to have been caused by a resistant pathogen. However, these results were not unexpected.
“If a child receiving TMP/SMX prophylaxis, a recurrence would most likely be caused by a resistant pathogen,” he said. “We would always switch to a different antibiotic for treatment, usually a third-generation cephalosporin.”
Regarding imaging recommendations in the 2011 AAP clinical practice guideline for diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months, Hoberman said that these findings from the RIVUR study will permit decision analysis and cost-effectiveness analysis to clarify clinical and financial tradeoffs that would enable more informed decisions for clinicians and families.
“Our study provides unequivocal evidence that antimicrobial prophylaxis reduced at least in half the likelihood of children having recurrent 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,” Hoberman said during his presentation.
In an editorial accompanying the full study published in the NEJM, Julie R. Ingelfinger, MD, professor of pediatrics, Massachusetts General Hospital, and F. Bruder Stapleton, MD, Department of Pediatric Chair at Seattle Children’s Hospital, said the RIVUR study reported some significant findings and closely reflected “real life” situations regarding adherence to medication. However, the editorialists also said that some questions remain unanswered.
“ … The RIVUR study results would imply that the general recommendation of prophylactic antibiotics for VUR in young children awaits more evidence before universal adoption,” they wrote. — by Cassandra A. Richards
For more information:
Hoberman A. Abstract#2823.9. Presented at PAS 2014; May 2-6, 2014; Vancouver, Canada.
The RIVUR Trial Investigators. N Engl J Med. 2014; doi: 10.1056/NEJMoa1401811.
Ingelfinger JR. N Engl J Med. 2014; doi: 10.1056/NEJMe1404774.
Disclosure: Hoberman reports no relevant financial disclosures.
Perspective
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Richard F. Jacobs, MD
The RIVUR trial is extremely well done and helps to answer a very complex question related to the primary end point of recurrences of symptomatic UTIs in children. The lack of impact on the secondary end point is not surprising, especially considering the myriad of risk factors, multiple components of anatomy, pathophysiology and even antimicrobial resistance in these patients. The study is a wonderful foundation for further research and analysis for comparative effectiveness research to continue the dialogue on how to manage these children most appropriately. The authors’ discussion is well worth a good read by practicing pediatricians.
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