2004年至2018年期间从中国患者中分离出的耐碳青霉烯类复合菌的分子机制与流行病学
Molecular Mechanisms and Epidemiology of Carbapenem-Resistant Complex Isolated from Chinese Patients During 2004-2018.
作者信息
Liu Shixing, Huang Na, Zhou Cui, Lin Yishuai, Zhang Ying, Wang Lingbo, Zheng Xiangkuo, Zhou Tieli, Wang Zhongyong
机构信息
Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
出版信息
Infect Drug Resist. 2021 Sep 7;14:3647-3658. doi: 10.2147/IDR.S327595. eCollection 2021.
BACKGROUND
The emergence and spread of carbapenem-resistant complex (ECC) have posed a serious threat to human health worldwide. This study aimed to investigate the molecular mechanism of carbapenem resistance and its prevalence among ECC in China.
METHODS
A total of 1314 ECC clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University from 2004 to 2018. Sensitivity to antibiotics was determined using the agar dilution method. The production of carbapenemases and the prevalence of resistance-associated genes were investigated using PCR. The expression of outer membrane porin (OMP) genes (/) and cephalosporinase gene was analyzed by quantitative real-time PCR. The effect of efflux pump mechanism on carbapenem resistance was tested. ECC was typed by multilocus sequence typing (MLST).
RESULTS
In this study, 113 carbapenem-nonsusceptible ECC strains were identified. The prevalence rates of carbapenemase genes and were 12.4% (14/113) and 17.7% (20/113), and that of the extended-spectrum β-lactamase (ESBL) genes , , and were 28.3% (32/113), 27.4% (31/113), and 14.2% (16/113), respectively. Among 67 carbapenem-nonsusceptible ECC isolates producing non-carbapenemase, low expression of and overexpression of were found in 46 and 40 strains, respectively. In addition, the carbapenem resistance was related to the overexpression of the efflux pump in the study. Finally, the 113 carbapenem-nonsusceptible ECC strains were categorized into 39 different sequence types using MLST.
CONCLUSION
Carbapenem-nonsusceptible ECC strains producing non-carbapenemase were predominant. The low expression of OMP with the overexpression of cephalosporinase or production of ESBLs and overexpression of efflux pump might contribute to the resistance to carbapenem for carbapenem-nonsusceptible ECC strains producing non-carbapenemase. The and comprised the principal resistance mechanism of carbapenemase-producing ECC in the hospital, causing a threat to public health. Therefore, monitoring programs to prevent the emergence and further spread of antibiotic resistance are urgently needed.
背景
耐碳青霉烯类肠杆菌科细菌（ECC）的出现和传播对全球人类健康构成了严重威胁。本研究旨在探讨中国ECC中耐碳青霉烯类的分子机制及其流行情况。
方法
2004年至2018年期间，从温州医科大学附属第一医院收集了1314株ECC临床分离株。采用琼脂稀释法测定对抗生素的敏感性。采用聚合酶链反应（PCR）检测碳青霉烯酶的产生及耐药相关基因的流行情况。通过定量实时PCR分析外膜孔蛋白（OMP）基因（/）和头孢菌素酶基因的表达。测试了外排泵机制对碳青霉烯耐药性的影响。通过多位点序列分型（MLST）对ECC进行分型。
结果
本研究共鉴定出113株对碳青霉烯不敏感的ECC菌株。碳青霉烯酶基因和的流行率分别为12.4%（14/113）和17.7%（20/113），超广谱β-内酰胺酶（ESBL）基因、和的流行率分别为28.3%（32/113）、27.4%（31/113）和14.2%（16/113）。在67株产生非碳青霉烯酶的对碳青霉烯不敏感的ECC分离株中，分别在46株和40株中发现了低表达和高表达。此外，在本研究中，碳青霉烯耐药性与外排泵的高表达有关。最后，使用MLST将113株对碳青霉烯不敏感的ECC菌株分为39种不同的序列类型。
结论
产生非碳青霉烯酶的对碳青霉烯不敏感的ECC菌株占主导地位。对于产生非碳青霉烯酶的对碳青霉烯不敏感的ECC菌株，OMP低表达伴头孢菌素酶高表达或ESBLs产生以及外排泵高表达可能导致对碳青霉烯的耐药性。和构成了医院中产碳青霉烯酶ECC的主要耐药机制，对公共卫生造成威胁。因此，迫切需要监测计划以防止抗生素耐药性的出现和进一步传播。
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