title: The safety and efficacy of high-dose daptomycin combined with rifampicin for the treatment of Gram-positive osteoarticular infections.
abstract: OBJECTIVE
  Treatment of Gram-positive osteoarticular infections requires an adequate surgical approach combined with intensive antimicrobial therapy. The aim of this study was to evaluate the safety and efficacy of a combined regimen of high-dose daptomycin and rifampicin, in patients with various types of Gram-positive osteoarticular infections.
  
  
  METHODS
  This single centre, non-comparative, prospective study evaluated the safety and efficacy of a combined regimen of intravenous daptomycin (8 mg/kg/day) and oral rifampicin (600 mg/day) in patients with Gram-positive osteoarticular infections, with a minimal follow-up of one year. Creatine phosphokinase, transaminases, bilirubinaemia, and serum creatinine, were measured at baseline and regular intervals.
  
  
  RESULTS
  The median daily doses of daptomycin and rifampicin, administered for a median duration of 21 (range, 10-122) days to 16 patients (median age, 63.5 years; 11 males, five females) presenting with staphylococcal (n = 15) or streptococcal (n = 1) osteoarticular infections, were 8.15 (range, 6.6-8.9) mg/kg/day and 600 (range, 600-900) mg/day, respectively. The combined regimen of daptomycin and rifampicin was well tolerated by all except one patient, without requiring treatment adjustment or discontinuation. One patient developed allergic responses probably due to rifampicin after 42 days. Fifteen (94 %) patients showed favourable clinical and microbiological outcomes.
  
  
  CONCLUSIONS
  The combined regimen of high-dose daptomycin and rifampicin was well tolerated and may provide a useful alternative to standard glycopeptide therapy for Gram-positive osteoarticular infections.
authors.affiliation: Orthopaedic Surgery Service, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Kheeldass
authors.initials: K
authors.lastname: Jugun
authors.forename: Pierre
authors.initials: P
authors.lastname: Vaudaux
authors.forename: Jorge
authors.initials: J
authors.lastname: Garbino
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pagani
authors.forename: Pierre
authors.initials: P
authors.lastname: Hoffmeyer
authors.forename: Daniel
authors.initials: D
authors.lastname: Lew
authors.forename: Ilker
authors.initials: I
authors.lastname: Uçkay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017576:Daptomycin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000601:surgery; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D012293:Rifampin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin; D012293:Rifampin