中国防痨杂志2024，Vol.46Issue(12)：1442-1447,6.DOI:10.19982/j.issn.1000-6621.20240274
奥马环素对脓肿分枝杆菌体外抑菌及细胞内杀菌活性
In vitro inhibitory and intracellular bactericidal activity of omadacycline against Mycobacterium abscessus
摘要
Abstract
Objective:To evaluate the antimicrobial and bactericidal activities of omadacycline against Mycobacterium abscessus(MAB)and provide insights into optimizing drug combinations for the treatment of MAB infections.Methods:A total of 58 clinical isolates of MAB,obtained from patients at the Beijing Chest Hospital between 2015 and 2016,as well as a reference strain(ATCC 19977),were included in this study.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of omadacycline against the reference strain were measured using microdilution,alongside determining the MIC90 for the clinical isolates.The checkerboard assay was employed to evaluate the effects of drug combinations on the reference strain,while intracellular bactericidal activity was assessed to measure the drugs'efficacy against intracellular bacteria.Results:Omadacycline demonstrated MIC of 0.5 μg/ml and MBC of 4 μg/ml against the reference strain,with MIC90 of 0.5 μg/ml for the clinical isolates.Synergistic effects were observed when omadacycline was combined with clarithromycin,linezolid,and bedaquiline,with fractional inhibitory concentration indices(FICIs)of 0.250,0.375,and 0.375,respectively.Additive effects were noted when combined with clofazimine,azithromycin,and rifabutin,with FICIs of 0.750,0.625 and 0.560.The combination of omadacycline and bedaquiline produced the most substantial reduction in MBC,decreasing from 4 μg/ml to 0.05 μg/ml,representing a 98.75％reduction compared to omadacycline monotherapy.For intracellular bacteria,the combination of omadacycline and azithromycin demonstrated the most pronounced bactericidal effect at 24 hours,reducing the bacterial count from(7.02±0.06)log10 CFU to(5.36±0.10)log10 CFU(t=3.241,P＜0.001).At 48 hours,the combination of omadacycline and clofazimine reduced the intracellular bacterial load from(7.36±0.10)log10 CFU to(5.33±0.35)log10 CFU(t=8.265,P=0.004).Similarly,the combination of omadacycline and imipenem resulted in a reduction of intracellular bacteria from(6.87±0.15)log10 CFU to(5.10±0.17)log10 CFU(t=13.190,P＜0.001).The combination of omadacycline and linezolid reduced the intracellular bacterial count from(6.95±0.05)log10 CFU to(5.26±0.24)log10 CFU(t=11.920,P=0.005).Similarly,the combination of omadacycline and rifabutin lowered the intracellular bacterial load from(6.98±0.07)log10 CFU to(5.65±0.16)log10 CFU(t=13.440,P=0.001).Conclusion:Omadacycline combined with other drugs demonstrates significant inhibitory and bactericidal activity against MAB.These findings suggest that omadacycline holds promise as a therapeutic option for treating MAB infections.关键词
脓肿分枝杆菌/分枝杆菌感染/抗菌药/奥马环素/体外研究Key words
Mycobacterium abscessus/Mycobacterial infections/Antibacterial agents/Omadacycline/In vitro studies分类
医药卫生引用本文复制引用
马释然,陈素婷,黄海荣,段鸿飞..奥马环素对脓肿分枝杆菌体外抑菌及细胞内杀菌活性[J].中国防痨杂志,2024,46(12):1442-1447,6.基金项目
High Level Public Health Talents in Beijing(Academic leader-03-08) （Academic leader-03-08）
Science and Technology Plan Project of Tongzhou(2019-1-564) 北京市高层次公共卫生人才(学科带头人-03-08) （2019-1-564）
通州科技计划项目(2019-1-564) （2019-1-564）
