a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
b Infectious Diseases Department, Veterans Affairs Western New York Healthcare System , Buffalo , NY , USA.
Infect Dis (Lond). 2017 May;49(5):410-416. doi: 10.1080/23744235.2016.1277587. Epub 2017 Jan 24.
There is an urgent need to optimize therapeutic options in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who have failed conventional therapy. Two clinical isolates were obtained from a 68-year-old male with persistent MRSA bacteremia before and after the development of daptomycin nonsusceptibility. The pharmacodynamic activity of monotherapies and combinations of ceftaroline, daptomycin, cefoxitin, nafcillin and vancomycin were evaluated in time-kill experiments versus 10 CFU/mL of the pre- and post-daptomycin nonsusceptible MRSA isolates. Cefoxitin, nafcillin and vancomycin alone or in combination with ceftaroline failed to generate prolonged bactericidal activity against the post-daptomycin nonsusceptible isolate whereas a ceftaroline-daptomycin combination resulted in 6, 24 and 48 h log(CFU/mL) reductions of 3.90, 4.40 and 6.32. Population analysis profiles revealed a daptomycin heteroresistant subpopulation of the pre-daptomycin nonsusceptible MRSA isolate that expanded by >10,000× on daptomycin agar containing 2-16 mg/L in the post-daptomycin nonsusceptible isolate. Daptomycin and ceftaroline combinations may be promising against persistent MRSA bacteremia.
目前迫切需要优化耐甲氧西林金黄色葡萄球菌（MRSA）菌血症患者的治疗选择，这些患者在常规治疗失败后。从一名 68 岁的男性患者中获得了两个临床分离株，该患者在出现达托霉素不敏感之前和之后均存在持续性 MRSA 菌血症。在时间杀伤实验中，评估了头孢洛林、达托霉素、头孢西丁、萘夫西林和万古霉素单药治疗和联合治疗对 10 CFU/mL 达托霉素敏感和不敏感 MRSA 分离株的药效学活性。头孢西丁、萘夫西林和万古霉素单独或与头孢洛林联合治疗对达托霉素不敏感的分离株均不能产生持久的杀菌活性，而头孢洛林-达托霉素联合治疗可使后达托霉素不敏感分离株的 6、24 和 48 小时 log(CFU/mL)减少 3.90、4.40 和 6.32。群体分析谱显示，达托霉素敏感的 MRSA 分离株中存在达托霉素异耐药亚群，在达托霉素不敏感的分离株中，达托霉素琼脂中含有 2-16mg/L 的达托霉素时，该亚群的数量增加了>10000 倍。达托霉素和头孢洛林联合治疗可能对持续性 MRSA 菌血症有治疗前景。
