黏菌素或替加环素分别与3种抗菌药物联合对耐碳青霉烯类鲍曼不动杆菌的体外抗菌效果研究

A Study on the In Vitro Antibacterial Effects of Colistin or Tigecycline Combined with Three Antimicrobial Agents Against Carbapenem-resistant Acinetobacter Baumannii

  • 摘要:
    目的  分析黏菌素(colistin,COL)或替加环素(tigecycline,TGC)分别与亚胺培南(imipenem,IPM)、阿米卡星(amikacin,AMK)、头孢哌酮-舒巴坦(cefoperazone-sulbactam,CSL)联合使用对耐碳青霉烯类鲍曼不动杆菌(carbapenem-resistant Acinetobacter baumannii,CRAB)的体外抗菌效果,为临床微生物感染筛选有效联合治疗方案提供依据。
    方法  回顾性收集2023年6—12月南京医科大学附属淮安第一医院临床分离的非重复CRAB菌株;采用微量肉汤稀释法测定CRAB菌株对常用抗菌药物的最低抑菌浓度;采用棋盘稀释法进行体外联合药敏试验,并计算部分抑菌浓度指数以评价联合效应(协同、相加、无关、拮抗)。
    结果  共纳入48株CRAB菌株。以COL为基础的联合方案均对CRAB表现出良好的协同或相加作用,其中COL+IPM组的协同作用率最高(83.3%),COL+AMK组和COL+CSL组主要表现为相加作用(相加作用率分别为66.7%和70.8%);以TGC为基础的联合方案主要表现为相加或无关作用,其中TGC+CSL组的相加作用率最高(75.0%),TGC+AMK组的无关作用率最高(70.8%);6种联合方案均未发现拮抗作用。进一步分析表明,COL+IPM组与其他联合方案对CRAB的抗菌效果存在显著差异(P<0.001),其协同作用率显著高于其他5种联合方案(83.3%比12.5%, P<0.001)和以COL为基础的其他方案(83.3%比31.3%, P<0.001),相加作用率显著低于其他5种联合方案(16.7%比58.7%,P<0.001)和以COL为基础的其他方案(16.7%比68.7%,P<0.001);此外,在以COL为基础的联合方案中均未发现无关作用。
    结论  COL与IPM联用对CRAB的协同作用率最高,协同抗菌效果最优, 可作为临床治疗CRAB感染的经验性联合用药方案。

     

    Abstract:
    Objective  To analyze the in vitro antibacterial effects of colistin (COL) or tigecycline (TGC) in combination with imipenem (IPM), amikacin (AMK), and cefoperazone-sulbactam (CSL) against carbapenem-resistant Acinetobacter baumannii(CRAB), so as to provide evidence for screening effective combination regimens for clinical microbial infections.
    Methods  Non-duplicate CRAB strains isolated from clinical specimens between June and December 2023 at Huai'an First People's Hospital Affiliated to Nanjing Medical University were retrospectively collected. The minimum inhibitory concentrations of commonly used antimicrobial agents against these strains were determined using the broth microdilution method. In vitro combination susceptibility testing was performed using the checkerboard dilution method, and the fractional inhibitory concentration index was calculated to evaluate the combined effects (synergistic, additive, indifferent, antagonistic).
    Results  A total of 48 CRAB strains were included. COL-based combination regimens all exhibited favorable synergistic or additive effects against CRAB. Among them, the COL+IPM group showed the highest synergistic rate (83.3%), while the COL+AMK and COL+CSL groups primarily demonstrated additive effects (additive rates of 66.7% and 70.8%, respectively). TGC-based combination regimens mainly exhibited additive or indifferent effects, with the TGC+CSL group showing the highest additive rate (75.0%) and the TGC+AMK group showing the highest indifferent rate (70.8%). No antagonistic effects were observed in any of the six combination regimens. Further analysis revealed that the antibacterial effect of the COL+IPM group against CRAB was significantly different from that of the other combination regimens (P < 0.001). The synergistic rate of the COL+IPM group was significantly higher than that of the other five combination regimens (83.3% vs. 12.5%, P < 0.001) and that of the other COL-based regimens (83.3% vs. 31.3%, P < 0.001). The additive rate of the COL+IPM group was significantly lower than that of the other five combination regimens (16.7% vs. 58.7%, P < 0.001) and that of the other COL-based regimens (16.7% vs. 68.7%, P < 0.001). Additionally, no indifferent effects were observed in any of the COL-based combination regimens.
    Conclusions  The combination of COL and IPM demonstrates the optimal synergistic antibacterial effect against CRAB, with the highest synergistic rate, and can be used as an empirical combination regimen for the clinical treatment of CRAB infections.

     

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