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Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis

BACKGROUND: Antibiotic-resistant Klebsiella pneumoniae has emerged as a critical public health threat worldwide. Understanding the antimicrobial resistance mechanisms of multidrug-resistant K. pneumoniae (MDR-Kp) and its prevalence in time and space would provide clinical significance for managing p...

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Autores principales: Yang, Jing, Zhang, Kai, Ding, Chen, Wang, Song, Wu, Weiwei, Liu, Xiangqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474722/
https://www.ncbi.nlm.nih.gov/pubmed/37660028
http://dx.doi.org/10.1186/s12866-023-02974-y
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author Yang, Jing
Zhang, Kai
Ding, Chen
Wang, Song
Wu, Weiwei
Liu, Xiangqun
author_facet Yang, Jing
Zhang, Kai
Ding, Chen
Wang, Song
Wu, Weiwei
Liu, Xiangqun
author_sort Yang, Jing
collection PubMed
description BACKGROUND: Antibiotic-resistant Klebsiella pneumoniae has emerged as a critical public health threat worldwide. Understanding the antimicrobial resistance mechanisms of multidrug-resistant K. pneumoniae (MDR-Kp) and its prevalence in time and space would provide clinical significance for managing pathogen infection. METHODS: Eighteen clinical MDR-Kp strains were analyzed by whole genome sequencing (WGS), and the antimicrobial resistance genes and associated resistance mechanisms were compared with results obtained from the conventional microbiological test (CMT). The sequence homology across strains in our study and those previously collected over time from a wide geographical region was assessed by phylogenetic analysis. RESULTS: MDR-Kp strains were collected from eighteen patients who had received empirical treatment before strain collection, with sputum (83.3%, 15/18) being the primary source of clinical samples. The commonly received treatments include β-lactamase inhibitors (55.6%, 10/18) and carbapenems (50%, 9/18). Using CMT, we found that all 18 strains were resistant to aztreonam and ciprofloxacin, while 14 (77.8%) showed resistance to carbapenem. Polymyxin B and tigecycline were the only antibiotics to which MDR-Kp strains were sensitive. A total of 42 antimicrobial resistance mechanisms were identified by WGS, surpassing the 40 detected by the conventional method, with 25 mechanisms shared between the two techniques. Despite a 100% accuracy rate of WGS in detecting penicillin-resistant strains, the accuracy in detecting cephalosporin-resistant strains was only at 60%. Among all resistance genes identified by WGS, Klebsiella pneumoniae carbapenemase-2 (KPC-2) was present in all 14 carbapenem-resistant strains. Phenotypic analysis indicated that sequence type (ST) 11 isolates were the primary cause of these MDR-Kp infections. Additionally, phylogenic clustering analysis, encompassing both the clinical and MDR-Kp strains previously reported in China, revealed four distinct subgroups. No significant difference was observed in the sequence homology between K. pneumoniae strains in our study and those previously collected in East China over time. CONCLUSION: The application of WGS in identifying potential antimicrobial-resistant genes of MDR-Kp has demonstrated promising clinical significance. Comprehensive genomic information revealed by WGS holds the promise of guiding treatment decisions, enabling surveillance, and serving as a crucial asset in understanding antibiotic resistance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-023-02974-y.
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spelling pubmed-104747222023-09-03 Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis Yang, Jing Zhang, Kai Ding, Chen Wang, Song Wu, Weiwei Liu, Xiangqun BMC Microbiol Research BACKGROUND: Antibiotic-resistant Klebsiella pneumoniae has emerged as a critical public health threat worldwide. Understanding the antimicrobial resistance mechanisms of multidrug-resistant K. pneumoniae (MDR-Kp) and its prevalence in time and space would provide clinical significance for managing pathogen infection. METHODS: Eighteen clinical MDR-Kp strains were analyzed by whole genome sequencing (WGS), and the antimicrobial resistance genes and associated resistance mechanisms were compared with results obtained from the conventional microbiological test (CMT). The sequence homology across strains in our study and those previously collected over time from a wide geographical region was assessed by phylogenetic analysis. RESULTS: MDR-Kp strains were collected from eighteen patients who had received empirical treatment before strain collection, with sputum (83.3%, 15/18) being the primary source of clinical samples. The commonly received treatments include β-lactamase inhibitors (55.6%, 10/18) and carbapenems (50%, 9/18). Using CMT, we found that all 18 strains were resistant to aztreonam and ciprofloxacin, while 14 (77.8%) showed resistance to carbapenem. Polymyxin B and tigecycline were the only antibiotics to which MDR-Kp strains were sensitive. A total of 42 antimicrobial resistance mechanisms were identified by WGS, surpassing the 40 detected by the conventional method, with 25 mechanisms shared between the two techniques. Despite a 100% accuracy rate of WGS in detecting penicillin-resistant strains, the accuracy in detecting cephalosporin-resistant strains was only at 60%. Among all resistance genes identified by WGS, Klebsiella pneumoniae carbapenemase-2 (KPC-2) was present in all 14 carbapenem-resistant strains. Phenotypic analysis indicated that sequence type (ST) 11 isolates were the primary cause of these MDR-Kp infections. Additionally, phylogenic clustering analysis, encompassing both the clinical and MDR-Kp strains previously reported in China, revealed four distinct subgroups. No significant difference was observed in the sequence homology between K. pneumoniae strains in our study and those previously collected in East China over time. CONCLUSION: The application of WGS in identifying potential antimicrobial-resistant genes of MDR-Kp has demonstrated promising clinical significance. Comprehensive genomic information revealed by WGS holds the promise of guiding treatment decisions, enabling surveillance, and serving as a crucial asset in understanding antibiotic resistance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-023-02974-y. BioMed Central 2023-09-02 /pmc/articles/PMC10474722/ /pubmed/37660028 http://dx.doi.org/10.1186/s12866-023-02974-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Jing
Zhang, Kai
Ding, Chen
Wang, Song
Wu, Weiwei
Liu, Xiangqun
Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
title Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
title_full Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
title_fullStr Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
title_full_unstemmed Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
title_short Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
title_sort exploring multidrug-resistant klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474722/
https://www.ncbi.nlm.nih.gov/pubmed/37660028
http://dx.doi.org/10.1186/s12866-023-02974-y
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