title: Daptomycin, fosfomycin, or both for treatment of methicillin-resistant Staphylococcus aureus osteomyelitis in an experimental rat model.
abstract: The in vivo activities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistant Staphylococcus aureus (daptomycin MIC, 0.25 μg/ml; fosfomycin MIC, 0.5 μg/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistant S. aureus in 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log(10) CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases, Medical University of Vienna, Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Poeppl
authors.forename: S
authors.initials: S
authors.lastname: Tobudic
authors.forename: T
authors.initials: T
authors.lastname: Lingscheid
authors.forename: R
authors.initials: R
authors.lastname: Plasenzotti
authors.forename: N
authors.initials: N
authors.lastname: Kozakowski
authors.forename: H
authors.initials: H
authors.lastname: Lagler
authors.forename: A
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: H
authors.initials: H
authors.lastname: Burgmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017576:Daptomycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005578:Fosfomycin / Q000627:therapeutic use*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D017576:Daptomycin