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Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations

Background: Carbapenem resistant Klebsiella pneumoniae (cr-Kp) causes serious infections associated with a high mortality rate. The clinical efficacy of ceftazidime/avibactam (CZA), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) against cr-Kp is challenged by the emergence of resistant s...

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Autores principales: Muresu, Narcisa, Del Rio, Arcadia, Fox, Valeria, Scutari, Rossana, Alteri, Claudia, Are, Bianca Maria, Terragni, Pierpaolo, Sechi, Illari, Sotgiu, Giovanni, Piana, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854441/
https://www.ncbi.nlm.nih.gov/pubmed/36671211
http://dx.doi.org/10.3390/antibiotics12010010
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author Muresu, Narcisa
Del Rio, Arcadia
Fox, Valeria
Scutari, Rossana
Alteri, Claudia
Are, Bianca Maria
Terragni, Pierpaolo
Sechi, Illari
Sotgiu, Giovanni
Piana, Andrea
author_facet Muresu, Narcisa
Del Rio, Arcadia
Fox, Valeria
Scutari, Rossana
Alteri, Claudia
Are, Bianca Maria
Terragni, Pierpaolo
Sechi, Illari
Sotgiu, Giovanni
Piana, Andrea
author_sort Muresu, Narcisa
collection PubMed
description Background: Carbapenem resistant Klebsiella pneumoniae (cr-Kp) causes serious infections associated with a high mortality rate. The clinical efficacy of ceftazidime/avibactam (CZA), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) against cr-Kp is challenged by the emergence of resistant strains, making the investigation and monitoring of the main resistance mechanisms crucial. In this study, we reported the genome characterization of a Klebsiella pneumoniae strain isolated from a critically ill patient and characterized by a multidrug resistant (MDR) profile, including resistance to CZA, M/V, and I/R. Methods: An antimicrobial susceptibility test (AST) was performed by an automated system and E-test and results were interpreted following the EUCAST guidelines. Genomic DNA was extracted using a genomic DNA extraction kit and it was sequenced using the Illumina Nova Seq 6000 platform. Final assembly was manually curated and carefully verified for detection of antimicrobial resistance genes, porins modifications, and virulence factors. Results: The K. pneumoniae isolate belonged to sequence type ST512 and harbored 23 resistance genes, conferring resistance to all antibiotic classes, including blaKPC-31 and blaOXA-181, leading to carbapenems resistance. The truncation of OmpK35 and mutation OmpK36GD were also observed. Conclusions: The genomic characterization demonstrated the high resistant profile of new cr-Kp coharboring class A and D carbapenemases. The presence of KPC-31, as well as the detection of OXA-181 and porin modifications, further limit the therapeutic options, including the novel combinations of β-lactam/β-lactamase inhibitor antibiotics in patients with severe pneumonia caused by cr-Kp.
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spelling pubmed-98544412023-01-21 Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations Muresu, Narcisa Del Rio, Arcadia Fox, Valeria Scutari, Rossana Alteri, Claudia Are, Bianca Maria Terragni, Pierpaolo Sechi, Illari Sotgiu, Giovanni Piana, Andrea Antibiotics (Basel) Communication Background: Carbapenem resistant Klebsiella pneumoniae (cr-Kp) causes serious infections associated with a high mortality rate. The clinical efficacy of ceftazidime/avibactam (CZA), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) against cr-Kp is challenged by the emergence of resistant strains, making the investigation and monitoring of the main resistance mechanisms crucial. In this study, we reported the genome characterization of a Klebsiella pneumoniae strain isolated from a critically ill patient and characterized by a multidrug resistant (MDR) profile, including resistance to CZA, M/V, and I/R. Methods: An antimicrobial susceptibility test (AST) was performed by an automated system and E-test and results were interpreted following the EUCAST guidelines. Genomic DNA was extracted using a genomic DNA extraction kit and it was sequenced using the Illumina Nova Seq 6000 platform. Final assembly was manually curated and carefully verified for detection of antimicrobial resistance genes, porins modifications, and virulence factors. Results: The K. pneumoniae isolate belonged to sequence type ST512 and harbored 23 resistance genes, conferring resistance to all antibiotic classes, including blaKPC-31 and blaOXA-181, leading to carbapenems resistance. The truncation of OmpK35 and mutation OmpK36GD were also observed. Conclusions: The genomic characterization demonstrated the high resistant profile of new cr-Kp coharboring class A and D carbapenemases. The presence of KPC-31, as well as the detection of OXA-181 and porin modifications, further limit the therapeutic options, including the novel combinations of β-lactam/β-lactamase inhibitor antibiotics in patients with severe pneumonia caused by cr-Kp. MDPI 2022-12-21 /pmc/articles/PMC9854441/ /pubmed/36671211 http://dx.doi.org/10.3390/antibiotics12010010 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Muresu, Narcisa
Del Rio, Arcadia
Fox, Valeria
Scutari, Rossana
Alteri, Claudia
Are, Bianca Maria
Terragni, Pierpaolo
Sechi, Illari
Sotgiu, Giovanni
Piana, Andrea
Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations
title Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations
title_full Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations
title_fullStr Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations
title_full_unstemmed Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations
title_short Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations
title_sort genomic characterization of kpc-31 and oxa-181 klebsiella pneumoniae resistant to new generation of β-lactam/β-lactamase inhibitor combinations
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854441/
https://www.ncbi.nlm.nih.gov/pubmed/36671211
http://dx.doi.org/10.3390/antibiotics12010010
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