Risk factors for extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infection in the community in Denmark: a case-control study

OBJECTIVE: To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, as risk factors for ESBL E.coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with previous studies.

METHODS: Population-based case-control study including 339 cases with community-onset ESBL E. coli UTI in 2007-2012, 3,390 non-ESBL E. coli UTI controls, and 3,390 population controls. We investigated potential risk factors by estimating odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for sex, age, and comorbidity.

RESULTS: Comparing cases with non-ESBL E. coli UTI, PPI use yielded an OR of 1.6 (95% CI 1.2-2.0) and antibiotic exposure an OR of 1.4 (95% CI 1.1-1.8); these were driven by nitrofurantoin (OR 1.8; 95% CI 1.3-2.6) and macrolides (OR 1.7; 95% CI 1.2-2.3). Other risk factors included: prior hospitalization with 1-2 and >2 hospitalizations vs. none yielding ORs of 1.9 (95% CI 1.4-2.5) and 4.6 (95% CI 3.2-6.8), recent surgery (OR 2.0; 95% CI 1.5-2.8), renal disease (OR 2.2; 95% CI 1.4-3.4), chronic pulmonary disease (OR 1.4; 95% CI 1.0-2.0), and cancer (OR 1.5; 95% CI 1.1-2.1). Comparing cases with population controls, we found that most risk factors were also risk factors for non-ESBL UTI.

CONCLUSIONS: ESBL E.coli UTI were associated with previous hospitalization and surgery. Nitrofurantoin and macrolides augmented the risk. PPIs had a moderate effect but may be important facilitators of ESBL carriage, due to their widespread use.