Fu Ying, Zhu Yufeng, Zhao Feng, Yao Bingyan, Yu Yunsong, Zhang Jun, Chen Qiong
Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
Infect Drug Resist. 2024 Sep 4;17:3851-3861. doi: 10.2147/IDR.S474150. eCollection 2024.
Our aim was to elucidate the resistance mechanisms and assess the combined synergistic and bactericidal activities of aztreonam in combination with ceftazidime/avibactam (CZA), meropenem/vaborbactam (MEV), and imipenem/relebactam (IMR) against Enterobacterales strains producing dual carbapenemases.
Species identification, antimicrobial susceptibility testing and determination of carbapenemase type were performed for these strains. Plasmid sizes, plasmid conjugation abilities and the localization of carbapenemase genes were investigated. Whole-genome sequencing was performed for all strains and their molecular characteristics were analyzed. In vitro synergistic and bactericidal activities of the combination of aztreonam with CZA, MEV and IMR against these strains were determined using checkerboard assay and time-kill curve assay.
A total of 12 strains producing dual-carbapenemases were collected, including nine , two , and one . The most common dual-carbapenemase gene pattern observed was (n=4), followed by (n=3), (n=2), (n=1), (n=1) and (n=1). In each strain, the carbapenemase genes were found to be located on two distinct plasmids which were capable of conjugating from the original strain to the receipt strain J53. The results of the checkerboard synergy analysis consistently revealed good synergistic effects of the combination of ATM with CZA, MEV and IMR. Except for one strain, all strains exhibited significant synergistic activity and bactericidal activity between 2 and 8 hours.
Dual-carbapenemase-producing posed a significant threat to clinical anti-infection treatment. However, the combination of ATM with innovative -lactam/β-lactamase inhibitor compounds had proven to be an effective treatment option.
我们的目的是阐明对产双碳青霉烯酶的肠杆菌科菌株的耐药机制，并评估氨曲南与头孢他啶/阿维巴坦（CZA）、美罗培南/法硼巴坦（MEV）和亚胺培南/瑞来巴坦（IMR）联合使用时的协同和杀菌活性。
对这些菌株进行菌种鉴定、抗菌药物敏感性测试和碳青霉烯酶类型的测定。研究质粒大小、质粒接合能力和碳青霉烯酶基因的定位。对所有菌株进行全基因组测序并分析其分子特征。使用棋盘法和时间杀菌曲线法测定氨曲南与CZA、MEV和IMR联合使用对这些菌株的体外协同和杀菌活性。
共收集到12株产双碳青霉烯酶的菌株，包括9株肺炎克雷伯菌、2株大肠埃希菌和1株阴沟肠杆菌。观察到的最常见的双碳青霉烯酶基因模式是 blaKPC blaNDM（n = 4），其次是 blaKPC blaIMP（n = 3）、 blaNDM blaVIM（n = 2）、 blaKPC blaOXA-48（n = 1）、 blaNDM blaOXA-23（n = 1）和 blaIMP blaVIM（n = 1）。在每株菌株中，发现碳青霉烯酶基因位于两个不同的质粒上，这些质粒能够从原始菌株接合到受体菌株J53。棋盘协同分析结果一致显示氨曲南与CZA、MEV和IMR联合使用具有良好的协同作用。除1株菌株外，所有菌株在2至8小时之间均表现出显著的协同活性和杀菌活性。
产双碳青霉烯酶的肠杆菌科菌株对临床抗感染治疗构成重大威胁。然而，氨曲南与新型β-内酰胺/β-内酰胺酶抑制剂化合物联合使用已被证明是一种有效的治疗选择。
