Yehia Hoda, El Said Manal, Azmy Magda, Badawy Moushira, Mansy Soheir, Gohar Hamida, Madany Nadia
J Egypt Soc Parasitol. 2016 Apr;46(1):57-66. doi: 10.12816/0026150.
The prevalence of methicillin-resistant Staphyloccoccus aureus (MRSA) strains has presented a new challenge in antimicrobial medication. Linezolid is a new drug with potent activity on Gram-positive pathogens such as MRSA. The aim of the study was to investigate the in vitro activity of linezolid alone and in combination with imipenem, vancomycin or rifampicin to determine the most active therapy against MRSA strains. Twenty clinical MRSA strains were isolated from patients admitted to inpatient departments and outpatient clinics of Theodor Bilharz Research Institute. Standard strain MRSA ATCC 43300 was included as a control. The MICs of MRSA strains to linezolid, vancomycin, imipenem and rifampicin were evaluated using E test. Time-kill curve were used to assess the in vitro activity of linezolid (at 8x MIC) alone and in combination with imipenem (at 32x MIC), vancomycin or rifampicin (at 8x MIC). Scanning and transmission electron microscopy were performed to compare bacterial morphological alterations owing to the different combi- nations. Time-kill studies showed synergistic effect when linezolid combined with imipenem was tested against all the MRSA strains. Linezolid plus vancomycin or rifampicin combinations did not display any synergism or antagonism. Scanning and transmission electron microscopy observations confirmed the interactions observed in time kill experiments. Linezolid in combination with subinhibitory concentrations of imipenem can be bactericidal against MRSA strains and appears to be a promising combination for the treatment of MRSA infections. No synergistic activity was seen when the linezolid and vancomycin or rifampicin were combined. Linezolid could prevent the emergence of mutants resistant to rifampicin
耐甲氧西林金黄色葡萄球菌（MRSA）菌株的流行给抗菌药物治疗带来了新的挑战。利奈唑胺是一种对MRSA等革兰氏阳性病原体具有强效活性的新药。本研究的目的是调查利奈唑胺单独以及与亚胺培南、万古霉素或利福平联合使用时的体外活性，以确定针对MRSA菌株的最有效治疗方法。从 Theodor Bilharz 研究所住院部和门诊部收治的患者中分离出 20 株临床 MRSA 菌株。将标准菌株 MRSA ATCC 43300 作为对照。使用 E 试验评估 MRSA 菌株对利奈唑胺、万古霉素、亚胺培南和利福平的最低抑菌浓度（MIC）。采用时间杀菌曲线评估利奈唑胺（8 倍 MIC）单独以及与亚胺培南（32 倍 MIC）、万古霉素或利福平（8 倍 MIC）联合使用时的体外活性。进行扫描电子显微镜和透射电子显微镜检查，以比较不同组合导致的细菌形态变化。时间杀菌研究表明，利奈唑胺与亚胺培南联合用于所有 MRSA 菌株时均显示出协同作用。利奈唑胺加万古霉素或利福平的组合未显示出任何协同或拮抗作用。扫描电子显微镜和透射电子显微镜观察结果证实了时间杀菌实验中观察到的相互作用。利奈唑胺与亚抑菌浓度的亚胺培南联合使用可对 MRSA 菌株产生杀菌作用，似乎是治疗 MRSA 感染的一种有前景的联合用药。利奈唑胺与万古霉素或利福平联合使用时未观察到协同活性。利奈唑胺可预防对利福平耐药的突变体出现
