Evaluation of Combination Therapy for Clostridium Difficile Infections at an Academic Hospital

Abstract

Specific Aims: The incidence of non-response, recurrence, relapse, and rate of complications of Clostridium difficile infections treated with combination of metronidazole and vancomycin versus vancomycin or metronidazole alone over a one-year period by treatment and strain type (i.e. NAP1/BI/027) were evaluated. The incidence of mortality in patients with moderate to severe Clostridium difficile associated diarrhea prescribed metronidazole, vancomycin, or combination metronidazole plus vancomycin as initial therapy was also determined. Additionally, significant factors associated with the use of combination vancomycin-metronidazole as initial therapy for moderate to severe CDAD were characterized. Methods: T This retrospective medical record review has been approved by the Institutional Review Board. Adult patients with stool specimens tested for detection of Clostridium difficile toxin B by PCR between April 2010 and March 2011 at a tertiary care, academic medical center were evaluated. Patients were included in the study if diagnosed with moderate to severe disease and received either monotherapy with metronidazole, monotherapy with oral vancomycin, or combination therapy with metronidazole and oral vancomycin for at least 80% of the first 10 days of treatment. Patients who are discharged alive within 72 hours of admission or who received therapy for less than 48 hours were excluded. Main Results: All patients (N=411) with laboratory evidence of Clostridium difficile during the study time period were evaluated. A total of 26 subjects who received oral vancomycin monotherapy and 56 subjects who received oral vancomycin along with metronidazole for at least 80% of the first 10 days of treatment were identified. Of the subjects who received oral vancomycin monotherapy during the first ten days of therapy, 5 (19%) were classified has a treatment failure or died within the first 21 days of therapy and 5 (19%) had either a recurrence or reappearance of Clostridium difficile associated diarrhea between 22 and 65 days post start of therapy. Of the subjects who received a combination of oral vancomycin and metronidazole during the first 10 days of therapy, 14 (25%) were classified has a treatment failure or died within the first 21 days of therapy and 22 (39%) had either a recurrence or reappearance of Clostridium difficile associated diarrhea between 22 and 65 days post start of therapy. In the combination therapy group, 5 (9%) were reported to have an ileus, toxic megacolon, or necrotic bowel during the first 10 days of therapy. Conclusions: In this study, the subjects who received a combination of oral vancomycin and metronidazole had higher rates of clinical failure, death, and recurrence than subjects who received monotherapy. Current guideline statements recommend combination therapy only in patients with an ileus with Clostridium difficile-associated diarrhea.