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Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions

Ceftazidime-avibactam (CZA) is one of the best therapeutic options available for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. However, sporadic reports of CZA-resistant strains have been rapidly increasing in patients. Herein, we provide detailed case reports of...

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Autores principales: Bongiorno, Dafne, Bivona, Dalida A., Cicino, Claudia, Trecarichi, Enrico M., Russo, Alessandro, Marascio, Nadia, Mezzatesta, Maria Lina, Musso, Nicolò, Privitera, Grete F., Quirino, Angela, Scarlata, Giuseppe G. M., Matera, Giovanni, Torti, Carlo, Stefani, Stefania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851273/
https://www.ncbi.nlm.nih.gov/pubmed/36683697
http://dx.doi.org/10.3389/fcimb.2022.1010979
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author Bongiorno, Dafne
Bivona, Dalida A.
Cicino, Claudia
Trecarichi, Enrico M.
Russo, Alessandro
Marascio, Nadia
Mezzatesta, Maria Lina
Musso, Nicolò
Privitera, Grete F.
Quirino, Angela
Scarlata, Giuseppe G. M.
Matera, Giovanni
Torti, Carlo
Stefani, Stefania
author_facet Bongiorno, Dafne
Bivona, Dalida A.
Cicino, Claudia
Trecarichi, Enrico M.
Russo, Alessandro
Marascio, Nadia
Mezzatesta, Maria Lina
Musso, Nicolò
Privitera, Grete F.
Quirino, Angela
Scarlata, Giuseppe G. M.
Matera, Giovanni
Torti, Carlo
Stefani, Stefania
author_sort Bongiorno, Dafne
collection PubMed
description Ceftazidime-avibactam (CZA) is one of the best therapeutic options available for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. However, sporadic reports of CZA-resistant strains have been rapidly increasing in patients. Herein, we provide detailed case reports of the emergence of ceftazidime-avibactam resistance to identify their resistome and virulome using genomic molecular approaches. Sixteen isolates were collected from 13 patients at three hospitals in Catania and Catanzaro (Italy) between 2020-2021. Antimicrobial susceptibility was determined by broth microdiluition. The samples included in study were analyzed for resistome, virulome and Sequence Type (ST) using Whole Genome Sequencing (WGS). All strains were resistant to ceftazidime/avibactam, ciprofloxacin, extended-spectrum cephalosporins and aztreonam, 13/16 to meropenem, 8/16 to colistin and 7/16 to fosfomycin; 15/16 were susceptible to meropenem/vaborbactam; all strains were susceptible to cefiderocol. Molecular analysis showed circulation of three major clones: ST101, ST307 and ST512. In 10/16 strains, we found a bla (KPC-3) gene; in 6/16 strains, four different bla (KPC) variants (bla (KPC28-31-34-50)) were detected. A plethora of other beta-lactam genes (bla (SHV28-45-55-100-106-187-205-212), bla (OXA1-9-48), bla (TEM-181) and bla (CTX-M-15)) was observed; bla (OXA-9) was found in ST307 and ST512, instead bla (OXA48) in one out four ST101 strains. With regard to membrane permeability, ompK35 and ompK36 harbored frameshift mutations in 15/16 strains; analysis of ompK37 gene revealed that all strains harbored a non-functional protein and carry wild-type PBP3. There is an urgent need to characterize the mechanisms underlying carbapenem resistance and the intrinsic bacterial factors that facilitate the rapid emergence of resistance. Furthermore, it is becoming increasingly important to explore feasible methods for accurate detection of different KPC enzymes.
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spelling pubmed-98512732023-01-20 Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions Bongiorno, Dafne Bivona, Dalida A. Cicino, Claudia Trecarichi, Enrico M. Russo, Alessandro Marascio, Nadia Mezzatesta, Maria Lina Musso, Nicolò Privitera, Grete F. Quirino, Angela Scarlata, Giuseppe G. M. Matera, Giovanni Torti, Carlo Stefani, Stefania Front Cell Infect Microbiol Cellular and Infection Microbiology Ceftazidime-avibactam (CZA) is one of the best therapeutic options available for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. However, sporadic reports of CZA-resistant strains have been rapidly increasing in patients. Herein, we provide detailed case reports of the emergence of ceftazidime-avibactam resistance to identify their resistome and virulome using genomic molecular approaches. Sixteen isolates were collected from 13 patients at three hospitals in Catania and Catanzaro (Italy) between 2020-2021. Antimicrobial susceptibility was determined by broth microdiluition. The samples included in study were analyzed for resistome, virulome and Sequence Type (ST) using Whole Genome Sequencing (WGS). All strains were resistant to ceftazidime/avibactam, ciprofloxacin, extended-spectrum cephalosporins and aztreonam, 13/16 to meropenem, 8/16 to colistin and 7/16 to fosfomycin; 15/16 were susceptible to meropenem/vaborbactam; all strains were susceptible to cefiderocol. Molecular analysis showed circulation of three major clones: ST101, ST307 and ST512. In 10/16 strains, we found a bla (KPC-3) gene; in 6/16 strains, four different bla (KPC) variants (bla (KPC28-31-34-50)) were detected. A plethora of other beta-lactam genes (bla (SHV28-45-55-100-106-187-205-212), bla (OXA1-9-48), bla (TEM-181) and bla (CTX-M-15)) was observed; bla (OXA-9) was found in ST307 and ST512, instead bla (OXA48) in one out four ST101 strains. With regard to membrane permeability, ompK35 and ompK36 harbored frameshift mutations in 15/16 strains; analysis of ompK37 gene revealed that all strains harbored a non-functional protein and carry wild-type PBP3. There is an urgent need to characterize the mechanisms underlying carbapenem resistance and the intrinsic bacterial factors that facilitate the rapid emergence of resistance. Furthermore, it is becoming increasingly important to explore feasible methods for accurate detection of different KPC enzymes. Frontiers Media S.A. 2023-01-05 /pmc/articles/PMC9851273/ /pubmed/36683697 http://dx.doi.org/10.3389/fcimb.2022.1010979 Text en Copyright © 2023 Bongiorno, Bivona, Cicino, Trecarichi, Russo, Marascio, Mezzatesta, Musso, Privitera, Quirino, Scarlata, Matera, Torti and Stefani https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Bongiorno, Dafne
Bivona, Dalida A.
Cicino, Claudia
Trecarichi, Enrico M.
Russo, Alessandro
Marascio, Nadia
Mezzatesta, Maria Lina
Musso, Nicolò
Privitera, Grete F.
Quirino, Angela
Scarlata, Giuseppe G. M.
Matera, Giovanni
Torti, Carlo
Stefani, Stefania
Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions
title Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions
title_full Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions
title_fullStr Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions
title_full_unstemmed Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions
title_short Omic insights into various ceftazidime-avibactam-resistant Klebsiella pneumoniae isolates from two southern Italian regions
title_sort omic insights into various ceftazidime-avibactam-resistant klebsiella pneumoniae isolates from two southern italian regions
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851273/
https://www.ncbi.nlm.nih.gov/pubmed/36683697
http://dx.doi.org/10.3389/fcimb.2022.1010979
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