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Clin Infect Dis. 2019 Sep 3. pii: ciz871. doi: 10.1093/cid/ciz871. [Epub ahead of print]

Use of oral vancomycin for Clostridioides difficile Infection (CDI) and the risk of vancomycin-resistant Enterococci (VRE).

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IDEAS Center of Innovation, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.
Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
Antimicrobial Stewardship Task Force, Pharmacy Benefits Management Program, US Department of Veterans Affairs.
South Texas Veterans Affairs Health Care System, San Antonio, TX.
University of Utah Health, Salt Lake City, UT.



Vancomycin is now a preferred treatment for all cases of C. difficile infection (CDI), regardless of disease severity. Concerns remain that a large-scale shift to oral vancomycin may increase selection pressure for vancomycin-resistant Enterococci (VRE). We evaluated the risk of VRE following oral vancomycin or metronidazole treatment among patients with CDI.


We conducted a retrospective cohort study of patients with CDI in the US Department of Veterans Affairs health system between January 1, 2006 and December 31, 2016. Patients were included if they were treated with metronidazole or oral vancomycin and had no history of VRE in the previous year. Missing data were handled by multiple imputation of 50 datasets. Patients treated with oral vancomycin were compared to those treated with metronidazole after balancing on patient characteristics using propensity score matching in each imputed dataset. Patients were followed for VRE isolated from a clinical culture within 3 months.


Patients treated with oral vancomycin were no more likely to develop VRE within 3 months than metronidazole-treated patients (adjusted RR 0.96, 95% CI 0.77 - 1.20), equating to an absolute risk difference of -0.11% (95% CI -0.68 - 0.47%). Similar results were observed at 6 months and when including surveillance cultures.


Our results suggest that oral vancomycin and metronidazole are equally likely to impact patients' risk of VRE. In the setting of stable CDI incidence, replacement of metronidazole with oral vancomycin is unlikely to be a significant driver of increased risk of VRE at the patient level.


Clostridioides (Clostridium) difficile infection; metronidazole; oral vancomycin; vancomycin-resistant enterococci


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