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米诺环素、替加环素、环丙沙星和左氧氟沙星对……的抗菌作用:采用体外时间杀菌试验和体内斑马鱼动物模型

Antimicrobial Effects of Minocycline, Tigecycline, Ciprofloxacin, and Levofloxacin against Using In Vitro Time-Kill Assays and In Vivo Zebrafish Animal Models.

作者信息

Lin Jiun-Nong, Lai Chung-Hsu, Huang Yi-Han, Yang Chih-Hui

机构信息

Department of Critical Care Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.

Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.

出版信息

Antibiotics (Basel). 2021 Mar 10;10(3):285. doi: 10.3390/antibiotics10030285.

Abstract

is a multidrug-resistant pathogen. This study evaluated the antimicrobial activity of minocycline, tigecycline, ciprofloxacin, and levofloxacin using in vitro time-kill assays and in vivo zebrafish animal models. The strain ED853-49 was arbitrarily selected from a bacterial collection which was concomitantly susceptible to minocycline, tigecycline, ciprofloxacin, and levofloxacin. The antibacterial activities of single agents at 0.5-4 × minimum inhibitory concentration (MIC) and dual-agent combinations at 2 × MIC using time-kill assays were investigated. The therapeutic effects of antibiotics in -infected zebrafish were examined. Both minocycline and tigecycline demonstrated bacteriostatic effects but no bactericidal effect. Minocycline at concentrations ≥2 × MIC and tigecycline at concentrations ≥3 × MIC exhibited a long-standing inhibitory effect for 48 h. Bactericidal effects were observed at ciprofloxacin and levofloxacin concentrations of ≥3 × MIC within 24 h of initial inoculation. Rapid regrowth of occurred after the initial killing phase when ciprofloxacin was used, regardless of the concentration. Levofloxacin treatment at the concentration of ≥2 × MIC consistently resulted in the long-lasting and sustainable inhibition of bacterial growth for 48 h. The addition of minocycline or tigecycline weakened the killing effect of fluoroquinolones during the first 10 h. The minocycline-ciprofloxacin or minocycline-levofloxacin combinations achieved the lowest colony-forming unit counts at 48 h. Zebrafish treated with minocycline or a combination of minocycline and levofloxacin had the highest survival rate (70%). The results of these in vitro and in vivo studies suggest that the combination of minocycline and levofloxacin is the most effective therapy approach for infection.

摘要

是一种多重耐药病原体。本研究使用体外时间杀菌试验和体内斑马鱼动物模型评估了米诺环素、替加环素、环丙沙星和左氧氟沙星的抗菌活性。菌株ED853 - 49是从一个细菌菌库中随机选取的,该菌库对米诺环素、替加环素、环丙沙星和左氧氟沙星均敏感。采用时间杀菌试验研究了单药在0.5 - 4倍最小抑菌浓度(MIC)时以及双药联合在2倍MIC时的抗菌活性。检测了抗生素对感染斑马鱼的治疗效果。米诺环素和替加环素均表现出抑菌作用但无杀菌作用。浓度≥2倍MIC的米诺环素和浓度≥3倍MIC的替加环素表现出长达48小时的持久抑制作用。在初始接种后24小时内,环丙沙星和左氧氟沙星浓度≥3倍MIC时观察到杀菌作用。使用环丙沙星时,无论浓度如何,在初始杀菌阶段后均出现细菌快速再生长。浓度≥2倍MIC的左氧氟沙星治疗持续导致细菌生长受到持久且可持续的抑制达48小时。在最初10小时内,添加米诺环素或替加环素会削弱氟喹诺酮类药物的杀菌效果。米诺环素 - 环丙沙星或米诺环素 - 左氧氟沙星联合用药在48小时时菌落形成单位数最低。用米诺环素或米诺环素与左氧氟沙星联合治疗的斑马鱼存活率最高(70%)。这些体外和体内研究结果表明,米诺环素和左氧氟沙星联合是治疗该感染最有效的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7b/7999888/3c7a4c326de3/antibiotics-10-00285-g001.jpg

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