Prior antimicrobial drug exposure: a risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections

Objectives: Antimicrobial drug use is believed to be an important risk factor for the emerging problem of antimicrobial drug resistance, yet strong evidence for the causal relationship in community settings has been limited. Detailed analysis of this risk factor at the level of the individual patient has been hampered by limited availability of drug exposure data among patients with outpatient infections. We used a novel data system to identify patterns of individual antimicrobial drug exposures associated with trimethoprim-sulfamethoxazole-resistant urinary tract infections (UTIs). Materials and methods: This was a retrospective case-control study. Subjects were veterans with Gram-negative UTIs seen at the Philadelphia VA Medical Center from 1 July 1996 to 31 December 1999. Subjects were linked to a national VA outpatient pharmacy database. Cases and controls were identified based on the results of trimethoprim-sulfamethoxazole susceptibility testing. Results: Three hundred and ninety-three veterans with UTIs could be linked to electronic pharmacy records. The overall rate of trimethoprim-sulfamethoxazole drug resistance was 13%, without significant annual variation. Antimicrobial drug exposure within 6 months was strongly associated with the probability of a trimethoprim-sulfamethoxazole-resistant infection (OR = 4.1,95% Cl 2.2-7.5). This association extended to exposure to other antimicrobial drugs in addition to trimethoprim-sulfamethoxazole and the overall association displayed a dose-response relationship in terms of the number of prior drug exposures. Conclusions: Prior antimicrobial drug exposure is a strong risk factor for infection with trimethoprim-sulfamethoxazole-resistant Gram-negative bacteria among patients with UTIs.