title: Epidemiology of adverse events and Clostridium difficile-associated diarrhea during long-term antibiotic therapy for osteoarticular infections.
abstract: 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.
authors.affiliation: Orthopedic Surgery Service, Geneva University Hospitals & Faculty of Medicine, University of Geneva, Switzerland; Service of Rehabilitation, Geneva University Hospitals & Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schindler
authors.forename: Louis
authors.initials: L
authors.lastname: Bernard
authors.forename: Wilson
authors.initials: W
authors.lastname: Belaieff
authors.forename: Axel
authors.initials: A
authors.lastname: Gamulin
authors.forename: Guillaume
authors.initials: G
authors.lastname: Racloz
authors.forename: Stéphane
authors.initials: S
authors.lastname: Emonet
authors.forename: Daniel
authors.initials: D
authors.lastname: Lew
authors.forename: Pierre
authors.initials: P
authors.lastname: Hoffmeyer
authors.forename: Ilker
authors.initials: I
authors.lastname: Uçkay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001850:Bone Diseases, Infectious / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D016009:Chi-Square Distribution; D016360:Clostridioides difficile / Q000302:isolation & purification*; D015331:Cohort Studies; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology* / Q000382:microbiology; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016459:Prosthesis-Related Infections / Q000188:drug therapy / Q000453:epidemiology / Q000601:surgery; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: Adverse events; Clostridium difficile; Long-term antibiotic therapy; Orthopedic; Osteoarticular infections