Department of Internal Medicine I, Division of Infectious Diseases, Medical University of Vienna, Vienna, Austria.
Antimicrob Agents Chemother. 2011 Nov;55(11):4999-5003. doi: 10.1128/AAC.00584-11. Epub 2011 Aug 22.
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.
在耐甲氧西林金黄色葡萄球菌（万古霉素 MIC 为 0.25μg/ml，磷霉素 MIC 为 0.5μg/ml）的临床分离株的大鼠骨髓炎模型中，评估了达托霉素、磷霉素以及这两种抗生素联合应用的体内活性。共 37 只患有实验性骨髓炎的大鼠接受了为期 4 周的治疗，每天一次皮下给予 60mg/kg 体重的达托霉素、每天一次腹腔内给予 75mg/kg 体重的磷霉素、联合使用这两种药物或生理盐水安慰剂。治疗结束后，处死动物，对感染的胫骨进行定量细菌培养。骨培养物中发现 9/9（100%）安慰剂组、9/9（100%）达托霉素治疗组、1/10（10%）磷霉素治疗组和 9/9（22.2%）联合治疗组的动物均为耐甲氧西林金黄色葡萄球菌阳性。骨样本中的细菌计数结果表示为每克骨的 log(10)CFU，并使用曼-惠特尼 U 检验和 Bonferroni 多重比较检验进行分析。根据细菌计数，达托霉素治疗明显优于安慰剂组，尽管它仍然劣于磷霉素治疗组。联合治疗未观察到协同或拮抗作用。在 4 周的治疗期间，未观察到对达托霉素或磷霉素的耐药性发展。
