体外评估不同抗菌药物组合（含或不含多黏菌素）对碳青霉烯类耐药鲍曼不动杆菌临床分离株的作用。

In-vitro evaluation of different antimicrobial combinations with and without colistin against carbapenem-resistant Acinetobacter baumannii clinical isolates.

机构信息

Faculty of Medicine, Department of Medical Microbiology, İzmir Katip Çelebi University, İzmir, Türkiye.

Cizre Dr. Selahattin Cizrelioğlu Public Hospital, Department of Medical Microbiology, Şırnak, Türkiye.

出版信息

Eur J Med Res. 2024 Jun 16;29(1):331. doi: 10.1186/s40001-024-01885-6.

DOI:10.1186/s40001-024-01885-6

PMID:38880888

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11180387/

Abstract

BACKGROUND

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are one of the most common causes of nosocomial infections and have high mortality rates due to difficulties in treatment. In this study, the in vitro synergistic interactions of the colistin (CT)-meropenem (MEM) combination and patient clinical outcomes were compared in CRAB-infected patients that receive CT-MEM antimicrobial combination therapy. In addition, in vitro synergistic interactions of MEM-ertapenem (ETP), MEM-fosfomycin (FF) and CT-FF antimicrobial combinations were investigated. Finally, the epsilometer (E) test and checkerboard test results were compared and the compatibility of these two tests was evaluated.

METHODS

Twenty-one patients were included in the study. Bacterial identification was performed with MALDI-TOF, and antimicrobial susceptibility was assessed with an automated system. Synergy studies were performed using the E test and checkerboard method.

RESULTS

For the checkerboard method, the synergy rates for CT-MEM, MEM-FF, MEM-ETP and CT-FF were 100%, 52.3%, 23.8% and 28.5%, respectively. In the E test synergy tests, synergistic effects were detected for two isolates each in the CT-MEM and CT-FF combinations. Microbial eradication was achieved in nine (52.9%) of the 17 patients that received CT-MEM combination therapy. The agreement between the E test and the checkerboard test was 6.5%.

CONCLUSIONS

A synergistic effect was found with the checkerboard method for the CT-MEM combination in all isolates in our study, and approximately 70% of the patients benefited from treatment with this combination. In addition, more than half of the isolates showed a synergistic effect for the MEM-FF combination. Combinations of CT-MEM and MEM-FF may be options for the treatment of CRAB infections. However, a comprehensive understanding of the potential of the microorganism to develop resistant mutants under applied exposures, as well as factors that directly affect antimicrobial activity, such as pharmacokinetics/pharmacodynamics, is essential for providing treatment advice. We found a low rate of agreement between the E test method and the checkerboard test method in our study, in contrast to the literature. Comprehensive studies that compare clinical results with methods are needed to determine the ideal synergy test and interpretation method.

摘要

背景

耐碳青霉烯鲍曼不动杆菌（CRAB）感染是医院获得性感染的最常见原因之一，由于治疗困难，死亡率很高。在这项研究中，比较了接受多粘菌素（CT）-美罗培南（MEM）联合抗菌治疗的 CRAB 感染患者中 CT-MEM 联合的体外协同作用及其患者的临床结局。此外，还研究了 MEM-厄他培南（ETP）、MEM-磷霉素（FF）和 CT-FF 抗菌组合的体外协同作用。最后，比较了埃普索姆（E）试验和棋盘试验的结果，并评估了这两种试验的兼容性。

方法

本研究纳入了 21 名患者。采用基质辅助激光解吸电离飞行时间（MALDI-TOF）进行细菌鉴定，采用自动系统进行抗菌药物敏感性评估。采用 E 试验和棋盘法进行协同研究。

结果

对于棋盘法，CT-MEM、MEM-FF、MEM-ETP 和 CT-FF 的协同率分别为 100%、52.3%、23.8%和 28.5%。在 E 试验协同试验中，CT-MEM 和 CT-FF 组合中每个组合均检测到两种分离株具有协同作用。17 名接受 CT-MEM 联合治疗的患者中有 9 名（52.9%）微生物清除。E 试验和棋盘试验之间的一致性为 6.5%。

结论

在本研究中，所有分离株的棋盘法均显示 CT-MEM 联合具有协同作用，约 70%的患者受益于该联合治疗。此外，MEM-FF 组合的半数以上分离株显示出协同作用。CT-MEM 和 MEM-FF 的联合可能是治疗 CRAB 感染的选择。然而，全面了解微生物在应用暴露下产生耐药突变的潜力以及直接影响抗菌活性的因素（如药代动力学/药效学）对于提供治疗建议至关重要。与文献相比，我们发现本研究中 E 试验方法和棋盘试验方法之间的一致性率较低。需要进行全面的研究，将临床结果与方法进行比较，以确定理想的协同试验和解释方法。