title: Antimicrobial Resistance and Urinary Tract Infection Recurrence.
abstract: BACKGROUND
  The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial found that recurrent urinary tract infections (rUTI) with resistant organisms were more common in the trimethoprim-sulfamethoxazole prophylaxis (TSP) arm. We describe factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) resistance of rUTIs in RIVUR.
  
  
  METHODS
  Children aged 2 to 71 months with first or second UTI (index UTI) and grade I to IV vesicoureteral reflux (VUR) were randomized to TSP or placebo and followed for 2 years. Factors associated with TMP-SMX-resistant rUTI were evaluated.
  
  
  RESULTS
  Among 571 included children, 48% were <12 months old, 43% had grade II VUR, and 38% had grade III VUR. Recurrent UTI occurred in 34 of 278 children receiving TSP versus 67 of 293 children receiving placebo. Among those with rUTI, 76% (26/34) of subjects receiving TSP had TMP-SMX-resistant organisms versus 28% (19/67) of subjects receiving placebo (P < .001). The proportion of TMP-SMX-resistant rUTI decreased over time: in the TSP arm, 96% were resistant during the initial 6 months versus 38% resistant during the final 6 months; corresponding proportions for the placebo arm were 32% and 11%. Among children receiving TSP, 7 (13%) of 55 with TMP-SMX-resistant index UTI had rUTI, whereas 27 (12%) of 223 with TMP-SMX-susceptible index UTI had rUTI (adjusted hazard ratio 1.38, 95% confidence interval 0.54-3.56). Corresponding proportions in placebo arm were 17 (26%) of 65 and 50 (22%) of 228 (adjusted hazard ratio 1.33, 95% confidence interval 0.74-2.38).
  
  
  CONCLUSIONS
  Although TMP-SMX resistance is more common among children treated with TSP versus placebo, resistance decreased over time. Among children treated with TSP, there was no significant difference in UTI recurrence between those with TMP-SMX-resistant index UTI versus TMP-SMX-susceptible UTI.
authors.affiliation: Department of Urology, Boston Children's Hospital, Boston, Massachusetts; caleb.nelson@childrens.harvard.edu.
authors.forename: Caleb P
authors.initials: CP
authors.lastname: Nelson
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hoberman
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Nader
authors.initials: N
authors.lastname: Shaikh
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
authors.forename: Ron
authors.initials: R
authors.lastname: Keren
authors.affiliation: Department of Urology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Ranjiv
authors.initials: R
authors.lastname: Mathews
authors.affiliation: Department of Pediatric Urology, Women & Children's Hospital of Buffalo, Buffalo, New York;
authors.forename: Saul P
authors.initials: SP
authors.lastname: Greenfield
authors.affiliation: Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan;
authors.forename: Tej K
authors.initials: TK
authors.lastname: Mattoo
authors.affiliation: Department of Biostatistics, The University of North Carolina, Chapel Hill, North Carolina;
authors.forename: Nathan
authors.initials: N
authors.lastname: Gotman
authors.affiliation: Department of Biostatistics, The University of North Carolina, Chapel Hill, North Carolina;
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: Marva
authors.initials: M
authors.lastname: Moxey-Mims
authors.affiliation: Department of Biostatistics, The University of North Carolina, Chapel Hill, North Carolina;
authors.forename: Myra A
authors.initials: MA
authors.lastname: Carpenter
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Chesney
mesh_terms: D019072:Antibiotic Prophylaxis; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012008:Recurrence; D055502:Secondary Prevention; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000209:etiology; D014718:Vesico-Ureteral Reflux / Q000150:complications / Q000188:drug therapy*
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination