Is there a relationship between vancomycin-resistant enterococcal infection and Clostridium difficile infection?

The relationship between vancomycin or metronidazole treatment of Clostridium difficile-associated diarrhea (CDAD) and the occurrence of vancomycin-resistant enterococcus (VRE) infection was investigated by review of 18 case-control studies. Fifteen (83%) of 18 studies found vancomycin use, days of use, or grams used to be significantly associated with VRE infection or colonization. Intravenous vancomycin use was a significant risk in nine of 10 studies, and oral vancomycin use was a significant risk in three of four studies that stratified risk by route of administration. Although statistically associated, oral vancomycin use was so infrequent (25% in the study with the most use) that it is likely to have only a minor influence as a risk for VRE infection or colonization when compared with the much more widespread use of intravenous vancomycin. Metronidazole exposure was found to be a significant risk in four of five studies that specifically assessed this variable, but the indication for metronidazole use was not specified. Risk factors for both VRE infection and CDAD include antimicrobial exposure, number of antimicrobials, days of antimicrobial use, specific agents (third-generation cephalosporins, clindamycin, and imipenem), patient age, length of hospitalization, severity of underlying illness, use of electronic rectal thermometers, enteral feedings, environmental contamination, and contamination of the hands of health care workers.