Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains

Heteroresistance can lead to treatment failure and is difficult to detect by the methods currently employed by clinical laboratories. The aim of this study was to investigate the prevalence of the amikacin-heteroresistant Klebsiella pneumoniae strains and explore potential amikacin heteroresistance...

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Autores principales: Feiyang Zhang, Qin Li, Jiawei Bai, Manlin Ding, Xiangjin Yan, Guangxi Wang, Baoli Zhu, Yingshun Zhou
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/e8c8abe3a371456481bbb1426601a37d
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spelling oai:doaj.org-article:e8c8abe3a371456481bbb1426601a37d2021-12-02T10:07:01ZHeteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains1664-302X10.3389/fmicb.2021.682239https://doaj.org/article/e8c8abe3a371456481bbb1426601a37d2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.682239/fullhttps://doaj.org/toc/1664-302XHeteroresistance can lead to treatment failure and is difficult to detect by the methods currently employed by clinical laboratories. The aim of this study was to investigate the prevalence of the amikacin-heteroresistant Klebsiella pneumoniae strains and explore potential amikacin heteroresistance mechanism through whole-genome sequencing (WGS) and quantitative reverse-transcription PCR (qRT-PCR). In this study, 13 isolates (8.39%) were considered as amikacin-heteroresistant K. pneumoniae strains among a total of 155 K. pneumoniae strains. The majority of the heterogeneous phenotypes (11/13, 84.61%) was unstable and the minimal inhibitory concentrations (MICs) fully or partially reverted back to the level of susceptibility of the parental isolate. The frequency of heteroresistant subpopulation ranged from 2.94×10−7 to 5.59×10−6. Whole-genome sequencing and single-nucleotide variants (SNVs) analysis showed that there were different nucleotide and resultant amino acid alterations among an amikacin-heteroresistant strain S38 and the resistant subpopulation S38L in several genes. Quantitative reverse-transcription PCR analysis revealed that the increased expression of aminoglycoside resistance genes detected in amikacin-heteroresistant K. pneumoniae strains might be associated with amikacin heteroresistance. The findings raise concerns for the emergence of amikacin-heteroresistant K. pneumoniae strains and the use of amikacin as therapy for the treatment of multidrug-resistant K. pneumoniae strains.Feiyang ZhangQin LiJiawei BaiManlin DingXiangjin YanGuangxi WangBaoli ZhuYingshun ZhouFrontiers Media S.A.articleKlebsiella pneumoniaeamikacinheteroresistancecarbapenemmultidrug resistanceMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Klebsiella pneumoniae
amikacin
heteroresistance
carbapenem
multidrug resistance
Microbiology
QR1-502
spellingShingle Klebsiella pneumoniae
amikacin
heteroresistance
carbapenem
multidrug resistance
Microbiology
QR1-502
Feiyang Zhang
Qin Li
Jiawei Bai
Manlin Ding
Xiangjin Yan
Guangxi Wang
Baoli Zhu
Yingshun Zhou
Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
description Heteroresistance can lead to treatment failure and is difficult to detect by the methods currently employed by clinical laboratories. The aim of this study was to investigate the prevalence of the amikacin-heteroresistant Klebsiella pneumoniae strains and explore potential amikacin heteroresistance mechanism through whole-genome sequencing (WGS) and quantitative reverse-transcription PCR (qRT-PCR). In this study, 13 isolates (8.39%) were considered as amikacin-heteroresistant K. pneumoniae strains among a total of 155 K. pneumoniae strains. The majority of the heterogeneous phenotypes (11/13, 84.61%) was unstable and the minimal inhibitory concentrations (MICs) fully or partially reverted back to the level of susceptibility of the parental isolate. The frequency of heteroresistant subpopulation ranged from 2.94×10−7 to 5.59×10−6. Whole-genome sequencing and single-nucleotide variants (SNVs) analysis showed that there were different nucleotide and resultant amino acid alterations among an amikacin-heteroresistant strain S38 and the resistant subpopulation S38L in several genes. Quantitative reverse-transcription PCR analysis revealed that the increased expression of aminoglycoside resistance genes detected in amikacin-heteroresistant K. pneumoniae strains might be associated with amikacin heteroresistance. The findings raise concerns for the emergence of amikacin-heteroresistant K. pneumoniae strains and the use of amikacin as therapy for the treatment of multidrug-resistant K. pneumoniae strains.
format article
author Feiyang Zhang
Qin Li
Jiawei Bai
Manlin Ding
Xiangjin Yan
Guangxi Wang
Baoli Zhu
Yingshun Zhou
author_facet Feiyang Zhang
Qin Li
Jiawei Bai
Manlin Ding
Xiangjin Yan
Guangxi Wang
Baoli Zhu
Yingshun Zhou
author_sort Feiyang Zhang
title Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
title_short Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
title_full Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
title_fullStr Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
title_full_unstemmed Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains
title_sort heteroresistance to amikacin in carbapenem-resistant klebsiella pneumoniae strains
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/e8c8abe3a371456481bbb1426601a37d
work_keys_str_mv AT feiyangzhang heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT qinli heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT jiaweibai heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT manlinding heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT xiangjinyan heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT guangxiwang heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT baolizhu heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
AT yingshunzhou heteroresistancetoamikacinincarbapenemresistantklebsiellapneumoniaestrains
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