Yamagishi Yuka, Mikamo Hiroshige, Kato Hideo, Nishiyama Naoya, Asai Nobuhiro, Koizumi Yusuke, Sakanashi Daisuke, Suematsu Hiroyuki, Matsuura Katsuhiko, Hagihara Mao
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Pharmacy, Aichi Medical University Hospital, Japan.
J Infect Chemother. 2017 Jun;23(6):368-373. doi: 10.1016/j.jiac.2017.02.013. Epub 2017 Mar 23.
The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600 mg every 12 h for the treatment of complicated skin and skin structure infection (cSSSI) caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models.
Tedizolid phosphate and linezolid were used for all in vivo testing. A total of one MRSA and two P. anaerobius isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (Δlog CFU/ml) obtained in the treated mice after 24 h compared with the numbers in the starting control animals (0 h).
The tedizolid and linezolid MICs for MRSA was 0.25 and 2 μg/ml. Tedizolid MIC for P. anaerobius was 0.12 μg/ml, and linezolid MICs for two P. anaerobius isolates were 0.5 and 1 μg/ml. In mixed infection model, tedizolid therapy showed similar antimicrobial activities for one MRSA and two P. anaerobius isolates evaluated, compared with linezolid therapy. Additionally, when comparing the activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used.
In the neutropenic murine thigh infection model, human simulated exposures of tedizolid and linezolid resulted in similar efficacies against MRSA, even though single and mixed infection models were used. These data support the clinical utility of tedizolid for use against MRSA and P. anaerobius in the treatment of cSSSI.
本研究旨在比较在中性粒细胞减少小鼠大腿混合感染模型中，每日200mg替加环素与人模拟暴露以及每12小时600mg利奈唑胺用于治疗由耐甲氧西林金黄色葡萄球菌（MRSA）和厌氧消化链球菌引起的复杂性皮肤和皮肤结构感染（cSSSI）的抗菌活性。
所有体内试验均使用磷酸替加环素和利奈唑胺。共使用了1株MRSA和2株厌氧消化链球菌分离株。计算每种分离株的抗菌效力，即与起始对照动物（0小时）相比，治疗24小时后处理小鼠体内细菌数量的变化（Δlog CFU/ml）。
MRSA对替加环素和利奈唑胺的最低抑菌浓度（MIC）分别为0.25和2μg/ml。厌氧消化链球菌对替加环素的MIC为0.12μg/ml，利奈唑胺对2株厌氧消化链球菌分离株的MIC分别为0.5和1μg/ml。在混合感染模型中，与利奈唑胺治疗相比，替加环素治疗对评估的1株MRSA和2株厌氧消化链球菌分离株显示出相似的抗菌活性。此外，在比较单一感染模型和混合感染模型中替加环素和利奈唑胺单药治疗的活性时，使用混合感染模型时两种抗菌药物的抗菌活性均减弱。
在中性粒细胞减少小鼠大腿感染模型中，即使使用单一和混合感染模型，替加环素与人模拟暴露的利奈唑胺对MRSA的疗效相似。这些数据支持替加环素在治疗cSSSI中用于对抗MRSA和厌氧消化链球菌的临床实用性。
