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

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 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 approximately 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.

FIG. 1.

Concentration of VRE in stools of patients with preexisting VRE colonization who were treated with oral metronidazole versus oral vancomycin for C. difficile-associated disease. Day 0, before treatment on day of CDAD diagnosis. For the metronidazole group (n = 37), the number of subjects monitored to 1 to 5 days, 6 to 10 days, 11 to 15 days, 16 to 20 days, and 21 to 25 days were 37, 28 (76%), 22 (59%), 19 (51%), and 16 (43%), respectively. For the vancomycin group (n = 19), the number of subjects monitored to 1 to 5 days, 6 to 10 days, 11 to 15 days, 16 to 20 days, and 21 to 25 days were 19, 14 (74%), 11 (58%), 11 (58%), and 8 (42%), respectively. The durations of treatment (mean ± the SD) with metronidazole and vancomycin were 11.2 ± 1.9 and 12.1 ± 2.0, respectively. Error bars indicate the standard error.

FIG. 2.

Decrease in concentration of VRE in stools of 33 VRE-colonized control patients after discontinuation of anti-anaerobic antibiotic therapy regimens on day 0. None of the patients received antibiotic therapy after day 0, and none had received therapy for CDAD. The control patients were enrolled in two previous observational studies examining the effect on antibiotic therapy on concentration of VRE colonization (2, 6). Error bars indicate the standard error.