Outcomes of clostridium difficile-associated discase treated with metronidazole or vancomycin before and after the emergence of NAP1/027

OBJECTIVE: To reassess the comparative efficacy of vancomycin versus metronidazole in the treatment of Clostridium difficile-associated disease (CDAD) after the emergence in 2003 of the hypervirulent NAP1/027 strain. METHODS: A retrospective cohort study was conducted in a tertiary-care Canadian hospital among 1,616 patients treated initially with metronidazole (N =3D 1,360), vancomycin (N =3D 219), or both (N =3D 37), between 1991 and 2006, and followed for 60 days after diagnosis. Primary outcome was severe/complicated CDAD (SC-CDAD) defined as any of: (a) death within 30 days, (b) septic shock, (c) megacolon, (d) perforation, or (e) emergency colectomy. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated, stratifying into pre-epidemic (1991\u962002) and epidemic (2003\u962006) periods. Secondary outcome was recurrence within 60 days. RESULTS: Risk factors for SC-CDAD were the same in both periods: age =3D65 yr, male sex, immunosuppression, hospital acquisition, tube feeding, short duration of diarrhea, fever, elevated leukocytosis, or creatinine. Adjusting for confounders and using metronidazole therapy as baseline, vancomycin therapy was associated with a lower probability of developing SC-CDAD in 1991\u962002 (AOR 0.21, 95% CI 0.05\u960.99, P =3D 0.048) but not during 2003\u962006 (AOR 0.90, 95% CI 0.53\u961.55, P =3D 0.71). For both metronidazole and vancomycin, risk of recurrence increased in 2003\u962004 but decreased in 2005\u962006. CONCLUSIONS: Loss of superiority of vancomycin over metronidazole coincided with the emergence of NAP1/027. Toxin hyperproduction by NAP1/027 might be such that the disease follows its natural course. Novel therapeutic approaches are needed. The higher risk of recurrence in 2003\u962004 probably reflected reinfections rather than relapses