关键词: Escherichia coli Klebsiella pneumoniae ST383 blaNDM-5 carbapenem resistance

Mesh : Ceftazidime / pharmacology Azabicyclo Compounds / pharmacology Humans Lebanon beta-Lactamases / genetics metabolism Klebsiella pneumoniae / genetics drug effects Whole Genome Sequencing Anti-Bacterial Agents / pharmacology Escherichia coli / genetics drug effects Carbapenems / pharmacology Drug Resistance, Multiple, Bacterial / genetics Drug Combinations Plasmids / genetics Microbial Sensitivity Tests Gene Transfer, Horizontal Genome, Bacterial Carbapenem-Resistant Enterobacteriaceae / genetics drug effects isolation & purification Bacterial Proteins / genetics metabolism Tertiary Care Centers

来  源:   DOI:10.3389/fcimb.2024.1407246   PDF(Pubmed)

Abstract:
UNASSIGNED: In the battle against multidrug-resistant bacterial infections, ceftazidime- avibactam (CZA) stands as a pivotal defense, particularly against carbapenemresistant (CR) Gram-negative pathogens. However, the rise in resistance against this drug poses a significant threat to its effectiveness, highlighting the critical need for in-depth studies about its resistance mechanisms.
UNASSIGNED: This research focuses on the genomic characterization of CR- and CZA-resistant Escherichia coli (n=26) and Klebsiella pneumoniae (n=34) strains, harboring the blaNDM and/or blaOXA-48-like genes, at a major Lebanese tertiary care medical center, using whole genome sequencing (WGS).
UNASSIGNED: Our findings revealed a notable prevalence of blaNDM in all K. pneumoniae strains isolates, with 27 of these also harboring blaOXA-48. On the other hand, E. coli strains predominantly carried the blaNDM-5 gene. Whole genome sequencing (WGS) identified a predominance of ST383 among K. pneumoniae strains, which possessed a multi-replicon IncFIB-IncHI1B plasmid harboring the blaNDM-5. Additionally, various Inc group plasmids in K. pneumoniae across multiple sequence types were found to carry the blaNDM. Similarly, diverse STs of E. coli were observed to carry blaNDM-5 on different plasmids.
UNASSIGNED: The study underscores NDM carbapenemases as a paramount resistance mechanism in Lebanon,jeopardizing critical last-resort treatments. It also illuminates the role of varied sequence types and mobile genetic elements in the spread of NDM resistance,stressing the urgent need for strategies to mitigate this threat, especially in nosocomial infections.
摘要:
在对抗多重耐药细菌感染的斗争中,头孢他啶-阿维巴坦(CZA)是一个关键的防御,特别是针对耐碳青霉烯(CR)革兰氏阴性病原体。然而,对这种药物的耐药性上升对其有效性构成了重大威胁,强调迫切需要深入研究其抗性机制。
本研究集中于对CR和CZA耐药的大肠杆菌(n=26)和肺炎克雷伯菌(n=34)菌株的基因组特征,携带blaNDM和/或blaOXA-48样基因,在黎巴嫩一家主要的三级医疗中心,使用全基因组测序(WGS)。
我们的发现揭示了blaNDM在所有肺炎克雷伯菌分离株中的显著流行,其中27个也藏有blaOXA-48。另一方面,大肠杆菌菌株主要携带blaNDM-5基因。全基因组测序(WGS)确定ST383在肺炎克雷伯菌菌株中占主导地位,其具有包含blaNDM-5的多复制子IncFIB-IncHI1B质粒。此外,发现肺炎克雷伯氏菌中跨多种序列类型的各种Inc组质粒携带blaNDM。同样,观察到大肠杆菌的不同ST在不同质粒上携带blaNDM-5。
该研究强调NDM碳青霉烯酶是黎巴嫩最重要的耐药机制,危及关键的最后手段治疗。它还阐明了不同序列类型和可移动遗传元件在NDM抗性传播中的作用,强调迫切需要减轻这一威胁的战略,尤其是在医院感染中。
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