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Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae

INTRODUCTION: Increasing occurrence of infections caused by multidrug-resistant Gram-negative bacteria resulted in colistin being the last agent for treatment. Apart from plasmid-mediated mcr genes, mutations involving several genes like mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC genes, are leadi...

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Autores principales: Bir, Raunak, Gautam, Hitender, Arif, Nazneen, Chakravarti, Priyanka, Verma, Jyoti, Banerjee, Sayantan, Tyagi, Sonu, Mohapatra, Sarita, Sood, Seema, Dhawan, Benu, Chaudhry, Rama, Kapil, Arti, Das, Bimal Kumar, Das, Bhabatosh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883296/
https://www.ncbi.nlm.nih.gov/pubmed/35237435
http://dx.doi.org/10.1177/20499361221080650
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author Bir, Raunak
Gautam, Hitender
Arif, Nazneen
Chakravarti, Priyanka
Verma, Jyoti
Banerjee, Sayantan
Tyagi, Sonu
Mohapatra, Sarita
Sood, Seema
Dhawan, Benu
Chaudhry, Rama
Kapil, Arti
Das, Bimal Kumar
Das, Bhabatosh
author_facet Bir, Raunak
Gautam, Hitender
Arif, Nazneen
Chakravarti, Priyanka
Verma, Jyoti
Banerjee, Sayantan
Tyagi, Sonu
Mohapatra, Sarita
Sood, Seema
Dhawan, Benu
Chaudhry, Rama
Kapil, Arti
Das, Bimal Kumar
Das, Bhabatosh
author_sort Bir, Raunak
collection PubMed
description INTRODUCTION: Increasing occurrence of infections caused by multidrug-resistant Gram-negative bacteria resulted in colistin being the last agent for treatment. Apart from plasmid-mediated mcr genes, mutations involving several genes like mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC genes, are leading causes of colistin resistance. Four colistin susceptibility testing methods were compared against broth microdilution (BMD) and determined the presence of the mcr1-5 gene. METHODOLOGY: A total of 100 carbapenem-resistant Enterobacterales isolates were tested for colistin susceptibility by commercial broth microdilution (cBMD), E-test, VITEK-2, and rapid polymyxin NP assay (RPNP) and compared with BMD. The presence of the mcr1-5 gene was determined by modified RPNP and PCR. Two non-mcr colistin-resistant XDR isolates were subjected to whole-genome sequencing using Illumina MiSeq sequencing platform. RESULTS: Among 100 carbapenem-resistant Enterobacterales isolates, 15% were resistant to colistin. Essential agreement, categorical agreement, major error, and very major error for cBMD/E-test/VITEK-2/RPNP were 96%/73%/82%/NA; 99%/86%/88%/91%, 1.2%/9.4%/11.8%/8.2% and 0%/40%/13.3%/13.3%, respectively. Only one Klebsiella pneumoniae isolate harbored the mcr-1 gene, observed by both methods. Whole-genome sequencing of two non-mcr XDR Klebsiella pneumoniae showed multiple mutations in 10 genes responsible for lipopolysaccharide biosynthesis. CONCLUSIONS: The performance of cBMD was excellent, whereas the E-test was unacceptable. VITEK-2 and RPNP performed better but remained unreliable due to high error rates. Multiple mutations in the target proteins involving lipopolysaccharide formation, modification, and regulation were seen, resulting in colistin resistance.
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spelling pubmed-88832962022-03-01 Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae Bir, Raunak Gautam, Hitender Arif, Nazneen Chakravarti, Priyanka Verma, Jyoti Banerjee, Sayantan Tyagi, Sonu Mohapatra, Sarita Sood, Seema Dhawan, Benu Chaudhry, Rama Kapil, Arti Das, Bimal Kumar Das, Bhabatosh Ther Adv Infect Dis Original Research INTRODUCTION: Increasing occurrence of infections caused by multidrug-resistant Gram-negative bacteria resulted in colistin being the last agent for treatment. Apart from plasmid-mediated mcr genes, mutations involving several genes like mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC genes, are leading causes of colistin resistance. Four colistin susceptibility testing methods were compared against broth microdilution (BMD) and determined the presence of the mcr1-5 gene. METHODOLOGY: A total of 100 carbapenem-resistant Enterobacterales isolates were tested for colistin susceptibility by commercial broth microdilution (cBMD), E-test, VITEK-2, and rapid polymyxin NP assay (RPNP) and compared with BMD. The presence of the mcr1-5 gene was determined by modified RPNP and PCR. Two non-mcr colistin-resistant XDR isolates were subjected to whole-genome sequencing using Illumina MiSeq sequencing platform. RESULTS: Among 100 carbapenem-resistant Enterobacterales isolates, 15% were resistant to colistin. Essential agreement, categorical agreement, major error, and very major error for cBMD/E-test/VITEK-2/RPNP were 96%/73%/82%/NA; 99%/86%/88%/91%, 1.2%/9.4%/11.8%/8.2% and 0%/40%/13.3%/13.3%, respectively. Only one Klebsiella pneumoniae isolate harbored the mcr-1 gene, observed by both methods. Whole-genome sequencing of two non-mcr XDR Klebsiella pneumoniae showed multiple mutations in 10 genes responsible for lipopolysaccharide biosynthesis. CONCLUSIONS: The performance of cBMD was excellent, whereas the E-test was unacceptable. VITEK-2 and RPNP performed better but remained unreliable due to high error rates. Multiple mutations in the target proteins involving lipopolysaccharide formation, modification, and regulation were seen, resulting in colistin resistance. SAGE Publications 2022-02-26 /pmc/articles/PMC8883296/ /pubmed/35237435 http://dx.doi.org/10.1177/20499361221080650 Text en © The Author(s), 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Bir, Raunak
Gautam, Hitender
Arif, Nazneen
Chakravarti, Priyanka
Verma, Jyoti
Banerjee, Sayantan
Tyagi, Sonu
Mohapatra, Sarita
Sood, Seema
Dhawan, Benu
Chaudhry, Rama
Kapil, Arti
Das, Bimal Kumar
Das, Bhabatosh
Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae
title Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae
title_full Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae
title_fullStr Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae
title_full_unstemmed Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae
title_short Analysis of colistin resistance in carbapenem-resistant Enterobacterales and XDR Klebsiella pneumoniae
title_sort analysis of colistin resistance in carbapenem-resistant enterobacterales and xdr klebsiella pneumoniae
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883296/
https://www.ncbi.nlm.nih.gov/pubmed/35237435
http://dx.doi.org/10.1177/20499361221080650
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