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Antimicrobial Agents and Chemotherapy, July 2008, p. 2403-2406, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00090-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Both Oral Metronidazole and Oral Vancomycin Promote Persistent Overgrowth of Vancomycin-Resistant Enterococci during Treatment of Clostridium difficile-Associated Disease{triangledown}

Wafa N. Al-Nassir,1 Ajay K. Sethi,2 Yuejin Li,3 Michael J. Pultz,3 Michelle M. Riggs,3 and Curtis J. Donskey3*

Department of Infectious Diseases, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, 10000 Euclid Avenue, Cleveland, Ohio,1 Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio,2 Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, Ohio3

Received 21 January 2008/ Returned for modification 22 March 2008/ Accepted 17 April 2008

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 concentrations were quantified. Eighty-seven subjects (97%) had received antibiotics within the past month. For 56 treatment courses in which preexisting 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 the 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.

* Corresponding author. Mailing address: Research Service, Louis Stokes Cleveland VA Medical Center, 10701 East Blvd., Cleveland, OH 44106. Phone: (216) 791-3800, ext. 5103. Fax: (216) 229-8509. E-mail: curtisd123{at}yahoo.com

{triangledown} Published ahead of print on 28 April 2008.

Antimicrobial Agents and Chemotherapy, July 2008, p. 2403-2406, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00090-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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