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抗甲氧西林耐药菌抗菌组合的协同潜力

Synergistic Potential of Antimicrobial Combinations Against Methicillin-Resistant .

作者信息

Yu Yang, Huang Han-Liang, Ye Xin-Qing, Cai Da-Tong, Fang Jin-Tao, Sun Jian, Liao Xiao-Ping, Liu Ya-Hong

机构信息

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.

出版信息

Front Microbiol. 2020 Aug 17;11:1919. doi: 10.3389/fmicb.2020.01919. eCollection 2020.

DOI:10.3389/fmicb.2020.01919
PMID:33013731
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7461988/
Abstract

The chemotherapeutic options for methicillin-resistant (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both and tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application.

摘要

耐甲氧西林金黄色葡萄球菌（MRSA）感染的化疗选择有限。由于多重耐药的MRSA，即使在临床情况下使用属于不同类别的抗生素，治疗失败也经常发生，就在最近。本研究旨在研究11种代表针对MRSA菌株不同作用机制的抗生素之间的相互作用，并为临床感染提供治疗策略。根据CLSI指南，通过肉汤微量稀释法或琼脂稀释法测定MRSA菌株的敏感性。通过相互分组，共评估了55种组合。通过药物相互作用试验检测潜在的协同作用，并进一步研究时间杀菌曲线和中性粒细胞减少小鼠感染模型。共有六种组合（万古霉素与利福平、万古霉素与苯唑西林、左氧氟沙星与苯唑西林、庆大霉素与苯唑西林、克林霉素与苯唑西林以及克林霉素与左氧氟沙星）对MRSA ATCC 43300菌株显示出协同活性。然而，在时间杀菌试验中，仅当万古霉素与苯唑西林或利福平联合使用时，才观察到对临床分离株#161402的抗菌活性。接下来，通过接种#161402的小鼠感染模型验证了万古霉素/苯唑西林和万古霉素/利福平的治疗效果。联合抗生素MIC以及细菌生长抑制和动态杀菌曲线进一步证明了万古霉素加苯唑西林和万古霉素加利福平对113株野生型MRSA菌株的抗菌协同作用。总之，万古霉素/利福平和万古霉素/苯唑西林在体外和体内试验中都是临床MRSA感染最具潜力的组合。左氧氟沙星/苯唑西林、庆大霉素/苯唑西林、克林霉素/苯唑西林和克林霉素/磷霉素的其他协同组合也被选中，但可能需要更多评估以进一步应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/c4c0ed8edf08/fmicb-11-01919-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/094963d7eecf/fmicb-11-01919-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/64c1d0631ced/fmicb-11-01919-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/48198be24161/fmicb-11-01919-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/c4c0ed8edf08/fmicb-11-01919-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/094963d7eecf/fmicb-11-01919-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/64c1d0631ced/fmicb-11-01919-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/48198be24161/fmicb-11-01919-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7127/7461988/c4c0ed8edf08/fmicb-11-01919-g004.jpg

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