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Abstract

Introduction: Clostridium difficile is implicated in 15%–25% of all cases of nosocomial antibiotic-associated diarrhea. Current guidelines recommend oral vancomycin 125 mg every six hours as the drug of choice for severe CDI. The recommendation is based on a retrospective analysis showing vancomycin to be superior to oral metronidazole for the treatment of severe disease, as well as data demonstrating no difference in outcomes between low (125 mg) and high (500 mg) dose vancomycin regimens. Despite this, many clinicians frequently prescribe higher doses (250, 500 mg) of oral vancomycin for severe CDI. While historical literature has suggested no benefit to increased doses of vancomycin, such data do not exist in the age of a more hypervirulent strain. Methods: This study evaluated adult patients admitted to four Detroit Medical Center hospitals hours with CDI confirmed by polymerase chain reaction and meeting severe CDI criteria. Patients received oral vancomycin 125mg every 6 hours (low dose), 250mg or 500mg every 6 hours (considered high dose for study purposes). Patients receiving concomitant CDI therapy were excluded. Exposure to concomitant antimicrobials was also collected. Groups were defined: low dose (LD) vs high dose (HD). P-values < 0.05 were considered significant. Results: From July 2010 to July 2012, this study included 137 CDI patients with a mean age of 67 years. LD group included 95 patients and HD group included 42. Baseline characteristics were similar between groups. Length of stay was 12 ± 9.6 LD v 11.8 ± 10.1 days HD, p=0.33. Duration of diarrhea was 4.2 days LD and 4.1 days HD, p=0.72. ICU admission was required in 28% LD patients and 26% HD, p=0.76. A mean of 2 non-CDI antimicrobials were received in 69% LD and 74% HD while on CDI therapy, p=0.61. Overall clinical cure was achieved in 74% LD and 67% HD, p=0.42. The overall mortality rate was not different between groups, 5.3% LD and 2.4% HD, p=0.67. Conclusions: Clostridium difficile is a very prevalent nosocomial infection. Many patients continue to receive concomitant antimicrobials while on CDI therapy. Increasing the dose of oral vancomycin for patients with severe CDI does not improve efficacy.