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[从各种临床样本中分离出的耐甲氧西林金黄色葡萄球菌菌株中磷霉素-替考拉宁联合用药的抗菌协同活性研究]

[Investigation of the Antibacterial Synergistic Activity of Fosfomycin-Teicoplanin Combination in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Various Clinical Sample].

作者信息

Biçer Rümeysa Tuba, Özekinci Tuncer, Koçoğlu Mücahide Esra

机构信息

İstanbul Medeniyet University Faculty of Medicine, Department of Medical Microbiology, İstanbul, Türkiye.

出版信息

Mikrobiyol Bul. 2024 Apr;58(2):113-124. doi: 10.5578/mb.202498156.

Abstract

The aim of this study was to investigate the detection of teicoplanin and fosfomycin antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) strains by different methods and to evaluate the antibacterial synergistic effect of teicoplanin-fosfomycin combination by using checkerboard assay and time kill curve assay. Forty-five MRSA strains isolated from clinical samples in routine medical microbiology laboratory of Göztepe Prof. Dr. Süleyman Yalçın City Hospital were included in the study. In the first stage of the combination study, minimum inhibitory concentrations (MIC) were investigated by broth microdilution for teicoplanin and by both broth microdilution and agar dilution methods for fosfomycin. The combination of teicoplanin and fosfomycin was tested by the checkerboard method in 45 MRSA strains and combination effect was determined according to fractional inhibitory concentration index (ΣFIC) calculation. The synergistic effect and bactericidal activity of antibiotic combination were studied against a randomly selected strain from the strains used in the study by using time-kill method for 24 hours. As a result of teicoplanin and fosfomycin antibiotic susceptibility studies, all isolates were found to be susceptible to both antibiotics according to the susceptibility breakpoints determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A synergistic effect was found in 22 (49%), additive effect in 22 (49%) and indifferent effect in one (2%) of the 45 strains studied with the checkerboard method. The mean ΣFIC of 45 isolates was found to be 0.5. In the combination study of the antibiotics of the isolate that was studied with time-kill method, synergism was detected for 1/8 MIC concentrations at 12th hour and 24th hour and synergism at 1/4 MIC concentration at sixth hour, 12th hour and 24th hour. In the combination study of 1/4 MIC concentrations of antibiotics, bactericidal effect was detected at sixth hour and this effect was observed to disappear at 12th and 24th hours. High rate of synergistic antibacterial effect of teicoplanin-fosfomycin combination on MRSA isolates was demonstrated as a result of in vitro tests. Such studies conducted on antibiotic-resistant bacterial infections will provide clinicians different treatment options and will contribute to increasing survival. As a result of this study, provided that it is supported by future clinical studies, it can be stated that the teicoplanin-fosfomycin combination may be an effective treatment option in community and hospital-acquired infections caused by MRSA.

摘要

本研究的目的是通过不同方法调查耐甲氧西林金黄色葡萄球菌(MRSA)菌株对替考拉宁和磷霉素的抗生素敏感性检测,并使用棋盘法和时间杀菌曲线法评估替考拉宁 - 磷霉素联合用药的抗菌协同作用。纳入了从戈兹特佩苏莱曼·亚尔钦教授市立医院常规医学微生物实验室临床样本中分离出的45株MRSA菌株。在联合研究的第一阶段,采用肉汤微量稀释法测定替考拉宁的最低抑菌浓度(MIC),采用肉汤微量稀释法和琼脂稀释法测定磷霉素的MIC。用棋盘法对45株MRSA菌株进行替考拉宁和磷霉素联合检测,并根据部分抑菌浓度指数(ΣFIC)计算确定联合效应。通过时间杀菌法对研究中随机选择的一株菌株进行24小时研究,以考察抗生素联合用药的协同效应和杀菌活性。根据欧洲抗菌药物敏感性试验委员会(EUCAST)确定的敏感性断点,替考拉宁和磷霉素抗生素敏感性研究结果显示,所有分离株对这两种抗生素均敏感。在45株用棋盘法研究的菌株中,发现22株(49%)有协同效应,22株(49%)有相加效应,1株(2%)有无关效应。45株分离株的平均ΣFIC为0.5。在用时间杀菌法研究的分离株的抗生素联合研究中,在第12小时和24小时检测到1/8 MIC浓度时有协同作用,在第6小时、12小时和24小时检测到1/4 MIC浓度时有协同作用。在抗生素1/4 MIC浓度的联合研究中,在第6小时检测到杀菌作用,在第12小时和24小时观察到这种作用消失。体外试验结果表明,替考拉宁 - 磷霉素联合用药对MRSA分离株具有较高的协同抗菌作用。针对耐药细菌感染进行的此类研究将为临床医生提供不同的治疗选择,并有助于提高生存率。作为本研究的结果,倘若得到未来临床研究的支持,可以说替考拉宁 - 磷霉素联合用药可能是治疗由MRSA引起 的社区和医院获得性感染的有效治疗选择。

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