Study of In Vitro Synergistic Bactericidal Activity of Dual beta-Lactam Antibiotics Against KPC-2-Producing Klebsiella pneumoniae
Study of In Vitro Synergistic Bactericidal Activity of Dual beta-Lactam Antibiotics Against KPC-2-Producing Klebsiella pneumoniae
复制标题
双β-内酰胺抗生素对产KPC-2肺炎克雷伯菌的体外协同杀菌活性研究
DOI：
10.1089/mdr.2019.0126
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发表时间：
2020
影响因子：
2.6
通讯作者：
Hu Fupin
中科院分区：
文献类型：
--
作者：
Zhang Wenxia;Guo Yan;Yang Yang;Dong Dong;Zheng Yonggui;Zhu Demei;Hu Fupin
目的：研究亚胺培南、美罗培南、头孢他啶、克拉维酸对40株产β-2肺炎克雷伯菌的体外协同杀菌活性，探索治疗耐碳青霉烯类肺炎克雷伯菌的新方案。用微量肉汤稀释法对全国5个城市的肺炎患者进行检测。用棋盘法测定了不同浓度的上述复合抗生素的体外协同杀菌活性。联合用药包括亚胺培南与克拉维酸、美罗培南与克拉维酸、亚胺培南与头孢他啶、美罗培南与头孢他啶、美罗培南与亚胺培南。用分数抑制浓度指数计算协同、无感和拮抗的综合效果。根据协同杀菌活性结果，筛选出16株进行时间杀灭试验。结果：40株OfK。肺炎克雷伯菌对各种抗菌药物均耐药，大多数菌株对碳青霉烯类抗生素的最低抑菌浓度为32 mg/L。所有的组合都不是对抗性的。亚胺培南与克拉维酸或亚胺培南与头孢他啶的协同作用分别为80%(32/40)和7.5%(3/40)，美罗培南与克拉维酸或美罗培南与头孢他啶的协同抗菌活性分别为25%(10/40)和30%(12/40)。美罗培南与亚胺培南联合用药的菌株占30%(12/40)。时间-杀灭分析验证了棋盘检验的数据。结论：本研究有力地支持了双重β-内酰胺类抗生素联合治疗产KpC-2-K感染可能有效的假说。肺炎。亚胺培南联合克拉维酸的疗效最好，其次是美罗培南-头孢他啶和亚胺培南-美罗培南。
Objectives:To study thein vitrosynergistic bactericidal activity of dual β-lactam antibiotics against KPC-2-producingKlebsiella pneumoniaeand to explore the new therapeutic regimens for infections caused by carbapenem-resistant strains.Materials and Methods:The antimicrobial susceptibility testing of imipenem, meropenem, ceftazidime, and clavulanic acid on 40 clinically isolated strains of KPC-2-producingK. pneumoniaefrom 5 cities across the country was performed by microdilution broth method. Thein vitrosynergistic bactericidal activity of combined antibiotics mentioned above was determined at various concentrations using checkerboard techniques. The combination of antibiotics include imipenem with clavulanic acid, meropenem with clavulanic acid, imipenem with ceftazidime, meropenem with ceftazidime, and meropenem with imipenem. The combined effectiveness of synergistic, indifferent, or antagonistic was calculated by fractional inhibitory concentration indexes. Based on the results of synergistic bactericidal activity, 16 strains were selected for time-kill assays.Results:All 40 strains ofK. pneumoniaewere shown resistant to every single antimicrobial agent tested, with minimal inhibitory concentrations of carbapenems >32 mg/L in most isolates. None of the combinations was antagonistic. Synergies of combination of imipenem with clavulanic acid, or imipenem with ceftazidime were observed in 80% (32/40) and 7.5% (3/40) of strains, respectively; Combinations of meropenem and clavulanic acid, or meropenem and ceftazidime revealed a synergistic antibacterial activity on 25% (10/40) and 30% (12/40) of strains, respectively. Synergy of meropenem and imipenem combination was shown in 30% (12/40) of strains. Time-kill assays validated the data from checkerboard testing.Conclusions:The study strongly supported the hypothesis that combined dual β-lactam antibiotics might be effective in the treatment of infections caused by KPC-2-producingK. pneumoniae. The combination of imipenem and clavulanic acid possessed the best efficiency, followed by the regimens of combined meropenem–ceftazidime and imipenem–meropenem.