Methods: A multicenter, retrospective cohort study comparing patients with severe CDAD treated with standard antibiotic therapy versus adjuvant tigecycline with standard therapy was performed. A total of 646 subjects were classified by illness severity using a scoring system derived from the Hines VA Clostridium difficile infection severity index. Seventy-nine patients had CDAD severity scores of 3 or higher. Of these, 46 recieved standard therapy and 31 received adjuvant tigecycline in addition to standard therapy. Characteristics of the 2 groups were statistically comparable in all measured variables, with the exception of CDAD severity score, which was higher in the tigecycline cohort (tigecycline: 4.06, standard therapy: 3.61, p = 0.002). The study compared all-cause 30-day mortality between the cohorts as its primary endpoint. Secondary endpoints were in-hospital mortality and incidence of colectomy as treatment for C. difficile. Outcomes were compared by binary logistic regression analysis, controlling for CDAD severity score.
Results: Tigecycline therapy was associated with significantly increased 30-day mortality compared to standard therapy for CDAD (odds ratio [OR] 2.898, 95% confidence interval [CI] 1.062-7.910, p=0.038). The tigecycline group also demonstrated significantly higher adjusted in-hospital mortality (OR 2.768, CI 1.019-7.518, p=0.046) and rates of colectomy (OR 11.13, CI 1.217- 101.7, p= 0.033).
Conclusion: Despite apparent efficacy against Clostridium difficile in vitro, tigecycline as adjunctive therapy for severe CDAD was associated with higher rates of colectomy and increased mortality. These findings raise concerns regarding the safety and efficacy of tigecycline for patients with severe Clostridium difficile infection.