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肯尼亚两家医疗机构(一家国家转诊医院和一家五级医院)中产超广谱β-内酰胺酶临床分离株的表型和基因型特征分析:肺炎克雷伯菌和大肠埃希菌

Phenotypic and Genotypic Characterization of Extended Spectrum Beta-Lactamase-Producing Clinical Isolates of and in Two Kenyan Facilities: A National Referral and a Level Five Hospital.

作者信息

Maveke Sylvia M, Aboge Gabriel O, Kanja Laetitia W, Mainga Alfred O, Gachau Naftaly, Muchira Beatrice W, Moriasi Gervason A

机构信息

Department of Public Health, Pharmacology, and Toxicology, University of Nairobi, P.O. Box 29053-00625, Nairobi, Kenya.

Department of Laboratory Medicine, Microbiology, Kenyatta National Hospital, P.O. Box 20723-00202, Nairobi, Kenya.

出版信息

Int J Microbiol. 2024 Feb 14;2024:7463899. doi: 10.1155/2024/7463899. eCollection 2024.

Abstract

BACKGROUND

The emergence of antimicrobial resistance (AMR) and multidrug resistance (MDR) among and , especially through the production of extended spectrum -lactamases (ESBLs), limits therapeutic options and poses a significant public health threat.

OBJECTIVE

The aim of this study was to assess the phenotypic and genetic determinants of antimicrobial resistance of ESBL-producing and isolates from patient samples in two Kenyan Hospitals.

METHODS

We collected 138 and 127 isolates from various clinical specimens at the two health facilities from January 2020 to February 2021. The isolates' ESBL production and antibiotic susceptibility were phenotypically confirmed using a standard procedure. Molecular analysis was done through conventional polymerase chain reaction (PCR) with appropriate primers for A, B, , , , , , , and genes, sequencing and BLASTn analysis.

RESULTS

Most (82.6%) and (92.9%) isolates were ESBL producers, with the highest resistance was against ceftriaxone (69.6% among and 91.3% among ) and amoxicillin/clavulanic acid (70.9% among ). The frequency of MDR was 39.9% among and 13.4% among isolates. The commonest MDR phenotypes among the isolates were CRO-FEP-AZM-LVX and CRO-AZM-LVX, while the FOX-CRO-AMC-MI-TGC-FM, FOX-CRO-FEP-AMC-TZP-AZM-LVX-MI and CRO-AMC-TZP-AZM-MI were the most frequent among isolates. Notably, the FOX-CRO-FEP-AMC-TZP-AZM-LVX-MI phenotype was observed in ESBL-positive and ESBL-negative isolates. The most frequent ESBL genes were (42%), (40.6%), and (36.2%) among , and (89%), (82.7%), (76.4%), and (72.5%) were most frequent ESBL genes among isolates. The and and genotypes were predominantly associated with FOX-CRO-FEP-MEM and CRO-FEP multidrug resistance (MDR) and CRO antimicrobial resistance (AMR) phenotypes, among isolates from Embu Level V (16.7%) and Kenyatta National Hospital (7.0%), respectively.

CONCLUSIONS

The high proportion of ESBL-producing and isolates increases the utilization of last-resort antibiotics, jeopardizing antimicrobial chemotherapy. Furthermore, the antimicrobial resistance patterns exhibited towards extended-spectrum cephalosporins, beta-lactam/beta-lactamase inhibitor combinations, fluoroquinolones, and macrolides show the risk of co-resistance associated with ESBL-producing isolates responsible for MDR. Hence, there is a need for regular surveillance and implementation of infection prevention and control strategies and antimicrobial stewardship programs.

摘要

背景

肠杆菌科细菌和铜绿假单胞菌中抗菌药物耐药性(AMR)和多重耐药性(MDR)的出现,尤其是通过产超广谱β-内酰胺酶(ESBLs),限制了治疗选择,并构成了重大的公共卫生威胁。

目的

本研究旨在评估肯尼亚两家医院患者样本中产ESBL的肠杆菌科细菌和铜绿假单胞菌分离株抗菌药物耐药性的表型和基因决定因素。

方法

2020年1月至2021年2月期间,我们从两家医疗机构的各种临床标本中收集了138株肠杆菌科细菌和127株铜绿假单胞菌分离株。使用标准程序对分离株的ESBL产生情况和抗生素敏感性进行表型确认。通过常规聚合酶链反应(PCR),使用针对A、B、C、D、E、F、G、H和I基因的适当引物进行分子分析、测序和BLASTn分析。

结果

大多数肠杆菌科细菌(82.6%)和铜绿假单胞菌(92.9%)分离株产ESBL,对头孢曲松的耐药性最高(肠杆菌科细菌中为69.6%,铜绿假单胞菌中为91.3%),对阿莫西林/克拉维酸的耐药性(肠杆菌科细菌中为70.9%)。多重耐药率在肠杆菌科细菌分离株中为39.9%,在铜绿假单胞菌分离株中为13.4%。肠杆菌科细菌分离株中最常见的多重耐药表型为CRO-FEP-AZM-LVX和CRO-AZM-LVX,而FOX-CRO-AMC-MI-TGC-FM、FOX-CRO-FEP-AMC-TZP-AZM-LVX-MI和CRO-AMC-TZP-AZM-MI在铜绿假单胞菌分离株中最常见。值得注意的是,在产ESBL阳性和阴性的肠杆菌科细菌分离株中均观察到FOX-CRO-FEP-AMC-TZP-AZM-LVX-MI表型。肠杆菌科细菌中最常见的ESBL基因是CTX-M(42%)、SHV(40.6%)和TEM(36.2%),铜绿假单胞菌分离株中最常见的ESBL基因是blaVIM(89%)、blaIMP(82.7%)、blaOXA-23(76.4%)和blaOXA-58(72.5%)。在来自恩布五级医院(16.7%)和肯雅塔国家医院(7.0%)的肠杆菌科细菌分离株中,CTX-M和SHV以及TEM基因型分别主要与FOX-CRO-FEP-MEM和CRO-FEP多重耐药(MDR)以及CRO抗菌药物耐药(AMR)表型相关。

结论

产ESBL的肠杆菌科细菌和铜绿假单胞菌分离株比例较高,增加了最后手段抗生素的使用,危及抗菌化疗。此外,对超广谱头孢菌素、β-内酰胺/β-内酰胺酶抑制剂组合、氟喹诺酮类和大环内酯类药物呈现的抗菌药物耐药模式表明,与产ESBL的多重耐药分离株相关的共耐药风险。因此,需要定期监测并实施感染预防与控制策略以及抗菌药物管理计划。

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