Epidemiology of adverse events and Clostridium difficile-associated diarrhea during long-term antibiotic therapy for osteoarticular infections

Objective: Osteoarticular infections require several weeks of antibiotic therapy, but little is known about the epidemiology of adverse events (AE) including symptomatic Clostridium difficile-associated diarrhea during treatment in these patients. Methods: Cohort study (1996-2011) at a tertiary hospital non-endemic for clostridial ribotype O27. Patients with previous C. difficile episodes and metronidazole treatment were excluded. Results: A total of 393 episodes were identified. Median age of patients was 69 years; 122 were immune-suppressed. All patients received antibiotic treatment for a median of 8 weeks, including 2 weeks intravenously (range, 0-9 weeks). Oral rifampin (600 mg/d) was used in combination in 167 (42%) episodes. A relatively small number of episodes (115/393; 29%) were complicated by AE (diarrhea, nausea, cholestasis, gastric intolerance to rifampin, rash, and mycosis), of which 41 (36%) led to treatment modification. AE occurred mainly after a median of 21 days. Fourteen patients (14/393; 3.6%) developed symptomatic C. difficile diarrhea. By multivariate Cox regression analysis, total duration of antibiotic therapy, and intravenous administration were significantly associated with AE (all p < 0.01). Regarding symptomatic C. difficile infection, rifampin (hazard ratio 0.21; 95% CI, 0.05-0.97) protected from diarrhea, but not gender or age. Hospital stay was significantly longer among patients with AE than patients without (median 78 vs. 42 d; p < 0.01). Conclusions: AE were frequent and were observed in 29% of patients treated for osteoarticular infections and prolonged the hospital stay. In contrast, diarrhea due to C. difficile was rare, while oral rifampin might act protectively against it. (c) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.