Duration of exposure to multiple antibiotics is associated with increased risk of vancomycin-resistant enterococcal bacteraemia: a nested case-control study

08 May 2018

Background. Vancomycin-resistant enterococcal (VRE) bacteraemia has a high mortality and continues to defy control. Antibiotic risk factors for VRE bacteraemia have not been adequately defined. We aimed to determine the risk factors for VRE bacteraemia focusing on duration of antibiotic exposure. Methods. A retrospective matched nested case-control study was conducted amongst hospitalised patients at Cambridge University Hospitals NHS Foundation Trust from 1st January 2006 to 31st December 2012. Cases who developed a first episode of VRE bacteraemia were matched 1:1 to controls by length of stay, year, specialty and ward type. Independent risk factors for VRE bacteraemia were evaluated using conditional logistic regression. Results. 235 cases were compared to 220 controls. Duration of exposure to parenteral vancomycin, fluoroquinolones, and meropenem were independently associated with VRE bacteraemia. Compared to patients with no exposure to vancomycin, those who received courses of 1-3 days, 4-7 days, or greater than 7 days had a stepwise increase in risk of VRE bacteraemia (conditional odds ratio (cOR) 1.2 (95% confidence interval [CI] 0.4-3.8), 3.8 (95% CI 1.2-11.7), and 6.6 (95% CI 1.9-22.8), respectively). Other risk factors were presence of central venous catheter (cOR 8.7 [95% CI 2.6-29.5]); neutropenia (cOR 15.5 [95% CI 4.2-57.0]); hypoalbuminaemia (cOR 8.5 [95% CI 2.4-29.5]); malignancy (cOR 4.4 [95% CI 1.6-12.0]); gastrointestinal disease (cOR 12.4 [95% CI 4.2-36.8]); or hepatobiliary disease (cOR 7.9 [95% CI 2.1-29.9]). Conclusions. Longer exposure to vancomycin, fluoroquinolones, or meropenem was associated with VRE bacteraemia. Antimicrobial stewardship interventions targeting high-risk antibiotics are required to complement infection control procedures against VRE bacteraemia.