Antimicrobial prophylaxis for children with vesicoureteral reflux.

TitleAntimicrobial prophylaxis for children with vesicoureteral reflux.
Publication TypeJournal Article
Year of Publication2014
AuthorsHoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews, iv R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA
Corporate AuthorsRIVUR Trial Investigators
JournalN Engl J Med
Volume370
Issue25
Pagination2367-76
Date Published2014 Jun
ISSN1533-4406
KeywordsAnti-Infective Agents, Urinary, Child, Child, Preschool, Double-Blind Method, Drug Resistance, Microbial, Female, Fever, Humans, Infant, Kaplan-Meier Estimate, Kidney, Male, Secondary Prevention, Trimethoprim-Sulfamethoxazole Combination, Urinary Tract Infections, Vesico-Ureteral Reflux
Abstract

BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial.

METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance.

RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group.

CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; RIVUR ClinicalTrials.gov number, NCT00405704.).

DOI10.1056/NEJMoa1401811
Alternate JournalN. Engl. J. Med.
PubMed ID24795142
PubMed Central IDPMC4137319
Grant ListK23 DK088943 / DK / NIDDK NIH HHS / United States
U01 DK074053 / DK / NIDDK NIH HHS / United States
U01 DK074053 / DK / NIDDK NIH HHS / United States
U01 DK074059 / DK / NIDDK NIH HHS / United States
U01 DK074062 / DK / NIDDK NIH HHS / United States
U01 DK074063 / DK / NIDDK NIH HHS / United States
U01 DK074064 / DK / NIDDK NIH HHS / United States
U01 DK074082 / DK / NIDDK NIH HHS / United States
UL1RR024153 / RR / NCRR NIH HHS / United States
UL1TR000003 / TR / NCATS NIH HHS / United States
UL1TR000005 / TR / NCATS NIH HHS / United States