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Effect of long-term trimethoprim/sulfamethoxazole treatment on resistance and integron prevalence in the intestinal flora: a randomized, double-blind, placebo-controlled trial in children.

Author(s): van der Veen EL, Schilder AG, Timmers TK, Rovers MM, Fluit AC, Bonten MJ, Leverstein-van Hall MA

Affiliation(s): Department of Otorhinolaryngology, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands. E.L.vanderVeen@umcutrecht.nl

Publication date & source: 2009-05, J Antimicrob Chemother., 63(5):1011-6. Epub 2009 Mar 18.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVES: The aim of this study was to test the hypothesis that trimethoprim/sulfamethoxazole selects for integron-positive and multidrug-resistant Enterobacteriaceae in the intestinal flora. METHODS: During 1 year of follow-up, antibiotic susceptibility and the presence of integrons were determined in faecal Enterobacteriaceae isolated from 99 children with chronic active otitis media, randomly assigned to treatment with trimethoprim/sulfamethoxazole or placebo (http://www.clinicaltrials.gov/; trial registration number NCT00189098). RESULTS: At 6 and 12 weeks of follow-up, 32 (91%) and 24 (67%) children in the trimethoprim/sulfamethoxazole group carried trimethoprim/sulfamethoxazole-resistant Enterobacteriaceae versus 10 (21%) and 8 (17%) children in the placebo group [rate differences (RDs): 70 (95% CI: 55; 85) and 50 (95% CI: 31; 69)], respectively. Multiresistance also increased during trimethoprim/sulfamethoxazole treatment. At 6 weeks of follow-up, the integron prevalence was 26 (79%) in the trimethoprim/sulfamethoxazole group and 10 (22%) in the placebo group [RD: 57 (95% CI: 39; 75)]. After 12 weeks the integron prevalence, and after 1 year the susceptibility levels, had returned to baseline values. CONCLUSIONS: Initially, trimethoprim/sulfamethoxazole usage was strongly associated with the appearance of integron-positive (multi)drug-resistant Enterobacteriaceae in the intestinal flora. After prolonged exposure to trimethoprim/sulfamethoxazole, however, this population of Enterobacteriaceae was substituted by a population with non-integron-associated resistance mechanisms. After trimethoprim/sulfamethoxazole was discontinued, susceptibility rates to all antibiotics returned to baseline levels.

Page last updated: 2009-10-20

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