Özer Bekir, Mataraci Kara Emel, Özbek Çelik Berna
Department of Pharmaceutical Microbiology, Institute of Graduate Studies in Health Sciences, University of Istanbul, 34116, Beyazıt, Istanbul, Turkey.
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University, 34116, Beyazit-Istanbul, Istanbul, Turkey.
J Antibiot (Tokyo). 2025 May;78(6):370-379. doi: 10.1038/s41429-025-00823-w. Epub 2025 May 7.
This study examines the effects of combining eravacycline with various antibiotics on carbapenem-resistant Enterobacterales (CRE) isolated from bloodstream infections. Fifty Enterobacterales isolates that produce the OXA-48 enzyme were tested for their Minimum Inhibitory Concentrations (MICs) using broth microdilution. The Mutant Prevention Concentrations (MPCs) of eravacycline, tigecycline, levofloxacin, colistin, fosfomycin, meropenem, and tobramycin were evaluated against CRE isolates. The bactericidal and synergistic effects of eravacycline, alone or in combination with other antibiotics, were assessed using time-kill curve (TKC) experiments. The in vitro synergistic activities of tested antibiotics in combination with eravacycline were also determined by microbroth checkerboard technique, and results were interpreted using the fractional inhibitory concentration (FIC) index. The results of our study demonstrated that colistin exhibited the best bactericidal activity and the highest susceptibility rates among the evaluated strains. Eravacycline exhibited lower MPC values compared to tigecycline when used alone. The results of the TCK method showed that the most effective synergistic interactions were observed when eravacycline was combined with levofloxacin, colistin, or meropenem. The results obtained by microbroth checkerboard techniques also described synergistic activity with all tested eravacycline combinations against tested clinical isolates of Enterobacterales. No antagonism was detected. The study's results indicate that the combination of eravacycline with colistin, meropenem, tobramycin or levofloxacin showed synergistic activity against strains of Enterobacterales that produce OXA-48. This combination therapy may be a viable alternative for treating carbapenemase-producing Enterobacterales bacteria. In addition, eravacycline's lower MPC value suggests it may avoid the emergence of resistant mutant strains in the population.
本研究考察了依拉环素与多种抗生素联合使用对从血流感染中分离出的耐碳青霉烯类肠杆菌科细菌（CRE）的影响。使用肉汤微量稀释法对50株产生OXA - 48酶的肠杆菌科细菌分离株进行最低抑菌浓度（MIC）检测。评估了依拉环素、替加环素、左氧氟沙星、黏菌素、磷霉素、美罗培南和妥布霉素对CRE分离株的突变预防浓度（MPC）。采用时间杀菌曲线（TKC）实验评估依拉环素单独或与其他抗生素联合使用时的杀菌和协同作用。还通过微量肉汤棋盘法测定了受试抗生素与依拉环素联合使用时的体外协同活性，并使用分数抑菌浓度（FIC）指数对结果进行解释。我们的研究结果表明，在评估的菌株中，黏菌素表现出最佳的杀菌活性和最高的敏感率。单独使用时，依拉环素的MPC值低于替加环素。TCK方法的结果表明，依拉环素与左氧氟沙星、黏菌素或美罗培南联合使用时观察到最有效的协同相互作用。微量肉汤棋盘法获得的结果也描述了所有受试的依拉环素联合用药对受试临床肠杆菌科细菌分离株具有协同活性。未检测到拮抗作用。研究结果表明，依拉环素与黏菌素、美罗培南、妥布霉素或左氧氟沙星联合使用对产生OXA - 48的肠杆菌科菌株具有协同活性。这种联合疗法可能是治疗产碳青霉烯酶肠杆菌科细菌的一种可行替代方案。此外，依拉环素较低的MPC值表明它可能避免群体中耐药突变菌株的出现。
