Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease

Department of Infectious Diseases, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, 10000 Euclid Avenue, Cleveland, Ohio; Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio; Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, Ohio

^* To whom correspondence should be addressed. Email: curtisd123{at}yahoo.com.

	Abstract

For treatment of mild to moderate Clostridium difficile-associated disease (CDAD), oral metronidazole has been recommended as the preferred agent, in part due to concern that vancomycin may be more likely to promote colonization by vancomycin-resistant enterococci (VRE). We performed a prospective observational study to examine the effects of oral metronidazole or vancomycin treatment of CDAD on acquisition and concentration of VRE stool colonization. Before, during, and after 90 courses of CDAD therapy, stool samples were cultured for VRE and the concentration was quantified. Eighty-seven subjects (97%) had received antibiotics within the past month. For 56 treatment courses in which pre-existing VRE colonization was present, metronidazole (n = 37 courses) and vancomycin (n = 19 courses) each promoted persistent VRE overgrowth during therapy, and the concentration decreased significantly in both groups by 2 weeks after completion of treatment (P <0.049). For 34 treatment courses in which baseline cultures were negative for VRE, new detection of VRE stool colonization occurred during 3 (14%) of the 22 courses of metronidazole and 1 (8%) of the 12 courses of vancomycin (P = 1.0). These results demonstrate that both oral metronidazole and oral vancomycin promote overgrowth of VRE during treatment of CDAD. New CDAD treatments are needed that are less likely to disrupt the intestinal microflora and promote overgrowth of healthcare-associated pathogens.