title: Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center.
abstract: BACKGROUND
  Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.
  
  
  METHODS
  We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves.
  
  
  RESULTS
  Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulase-negative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE.
  
  
  CONCLUSIONS
  Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded.
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France.|Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roux
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France.|Claude Bernard Lyon 1 University, Lyon, France.|International Center for Research in Infectiology, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Valour
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France.|Claude Bernard Lyon 1 University, Lyon, France.|Department of Infectious Diseases, William Morey Hospital, Chalon-sur-Saône, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Karsenty
authors.affiliation: Specialized Unit of Pharmacology, Hospices Civils de Lyon, Lyon, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perpoint
authors.affiliation: Claude Bernard Lyon 1 University, Lyon, France.|Department of Orthopaedic Surgery, Hospices Civils de Lyon, Lyon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lustig
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France.|Claude Bernard Lyon 1 University, Lyon, France.|International Center for Research in Infectiology, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
authors.affiliation: Department of Infectious Diseases, William Morey Hospital, Chalon-sur-Saône, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Martha
authors.affiliation: Claude Bernard Lyon 1 University, Lyon, France.|International Center for Research in Infectiology, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France.|Laboratory of Bacteriology, French National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France.|Claude Bernard Lyon 1 University, Lyon, France.|International Center for Research in Infectiology, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chidiac
authors.affiliation: Department of Infectious Diseases, Hospices Civils de Lyon - Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, 69317, Lyon, cedex 04, France. tristan.ferry@univ-lyon1.fr.|Claude Bernard Lyon 1 University, Lyon, France. tristan.ferry@univ-lyon1.fr.|International Center for Research in Infectiology, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France. tristan.ferry@univ-lyon1.fr.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017576:Daptomycin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007595:Joint Prosthesis / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin