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对产金属β-内酰胺酶且对氨曲南/阿维巴坦组合敏感的分离株的鉴定

Characterization of Metallo β-Lactamase Producing Isolates with Susceptibility to the Aztreonam/Avibactam Combination.

作者信息

Posteraro Brunella, De Maio Flavio, Spanu Teresa, Vidal Pereira Maria Alejandra, Fasano Francesca Romana, Sanguinetti Maurizio

机构信息

Unità Operativa "Medicina di Precisione in Microbiologia Clinica", Direzione Scientifica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

出版信息

Antibiotics (Basel). 2024 Dec 17;13(12):1221. doi: 10.3390/antibiotics13121221.

Abstract

Metallo-β-lactamases (MBLs) in and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT with the β-lactamase inhibitor avibactam (AVI) may restore its activity against MBL-producing isolates. AZT-AVI, along with other clinically relevant antimicrobials, was tested against thirteen MBL-producing clinical isolates of (nine , three , and one ) using whole-genome sequencing (WGS) for genetic characterization. AZT-AVI demonstrated full susceptibility across all isolates, whereas aztreonam alone was ineffective. The newer β-lactam/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam were inactive in 100% and 92.3% of isolates, respectively. WGS-based analysis revealed multiple resistance mechanisms consistent with MDR phenotypes, including high-risk clones (ST147 and ST11). AZT-AVI is effective against MDR MBL-producing , highlighting its therapeutic potential for challenging infections. While WGS does not replace phenotypic testing, it provides valuable insights for antimicrobial stewardship and the monitoring of resistance gene dissemination.

摘要

肠杆菌科细菌及其他革兰氏阴性菌中的金属β-内酰胺酶(MBLs)与多重耐药性(MDR)相关,对公众健康构成重大威胁。虽然氨曲南(AZT)可靶向产MBL的细菌,但其在表达其他可使其失活的β-内酰胺酶的细菌中疗效受损。将AZT与β-内酰胺酶抑制剂阿维巴坦(AVI)联合使用可能恢复其对产MBL分离株的活性。使用全基因组测序(WGS)对13株产MBL的临床分离株(9株肺炎克雷伯菌、3株大肠埃希菌和1株阴沟肠杆菌)进行遗传特征分析,并对AZT-AVI以及其他临床相关抗菌药物进行了测试。AZT-AVI对所有分离株均显示出完全敏感性,而单独使用氨曲南则无效。新型β-内酰胺/β-内酰胺酶抑制剂组合亚胺培南/瑞来巴坦和美罗培南/瓦博巴坦分别在100%和92.3%的分离株中无活性。基于WGS的分析揭示了与MDR表型一致的多种耐药机制,包括高风险克隆(ST147和ST11)。AZT-AVI对产MDR MBL的肠杆菌科细菌有效,突出了其在治疗挑战性感染方面的潜力。虽然WGS不能替代表型检测,但它为抗菌药物管理和耐药基因传播监测提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ae/11726746/ae935b4409b7/antibiotics-13-01221-g001.jpg

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