Park Kyung-Hwa, Greenwood-Quaintance Kerryl E, Mandrekar Jayawant, Patel Robin
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, South Korea.
Antimicrob Agents Chemother. 2016 Oct 21;60(11):6568-6572. doi: 10.1128/AAC.01248-16. Print 2016 Nov.
We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.
在耐甲氧西林金黄色葡萄球菌（MRSA）异物相关骨髓炎大鼠模型中，我们比较了单独使用替加环素、替加环素与利福平联合使用，以及利福平与万古霉素加用利福平的疗效。研究菌株为与人工关节感染相关的分离株。在未感染的大鼠中测定了腹腔注射替加环素、万古霉素和利福平的稳态药代动力学。将MRSA接种到胫骨近端，并植入一根金属丝。四周后，大鼠分别接受腹腔注射替加环素（n = 14）、替加环素加用利福平（n = 11）、利福平（n = 16）或万古霉素加用利福平（n = 13）治疗21天。17只大鼠未接受治疗。治疗后，进行了定量骨培养。采集血液以测定替加环素组和替加环素加用利福平组的药物谷浓度。替加环素的平均血浆峰浓度和从零到24小时的浓度-时间曲线下平均面积分别为12μg/ml和60μg·h/ml。所有治疗组的细菌载量均显著低于对照组；替加环素加用利福平治疗的动物与万古霉素加用利福平治疗的动物的细菌载量无显著差异。替加环素组的平均血浆谷浓度范围为0.44至0.73μg/ml。虽然从骨骼中分离出的菌株未检测到替加环素或万古霉素耐药，但利福平组10只动物（63%）、替加环素加用利福平组8只动物（73%）和万古霉素加用利福平组1只动物（8%）检测到利福平耐药。单独使用替加环素或替加环素与利福平联合使用在MRSA异物相关骨髓炎大鼠模型中具有活性。在接受替加环素加用利福平的动物中发现了利福平耐药的出现。
