Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic

Resistance to carbapenems in <i>Enterobacterales</i> has become a matter of the highest concern in the last decade. Recently, <i>Enterobacterales</i> harboring multiple carbapenemases were detected in three hospital centers in Croatia and in the outpatient setting, posing a s...

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Main Authors: Branka Bedenić, Josefa Luxner, Haris Car, Sanda Sardelić, Maja Bogdan, Dijana Varda-Brkić, Sandra Šuto, Andrea Grisold, Nataša Beader, Gernot Zarfel
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/12/5/677
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author Branka Bedenić
Josefa Luxner
Haris Car
Sanda Sardelić
Maja Bogdan
Dijana Varda-Brkić
Sandra Šuto
Andrea Grisold
Nataša Beader
Gernot Zarfel
author_facet Branka Bedenić
Josefa Luxner
Haris Car
Sanda Sardelić
Maja Bogdan
Dijana Varda-Brkić
Sandra Šuto
Andrea Grisold
Nataša Beader
Gernot Zarfel
author_sort Branka Bedenić
collection DOAJ
description Resistance to carbapenems in <i>Enterobacterales</i> has become a matter of the highest concern in the last decade. Recently, <i>Enterobacterales</i> harboring multiple carbapenemases were detected in three hospital centers in Croatia and in the outpatient setting, posing a serious therapeutic challenge for clinicians. In this study, we analyzed eight <i>Klebsiella pneumoniae</i> and two <i>Enterobacter cloacae</i> complex isolates with multiple carbapenemases, with regard to antibiotic susceptibility, β-lactamase production and plasmid content. The isolates demonstrated uniform resistance to amoxicillin/clavulanate, piperacillin/tazobactam, cefuroxime, ceftazidime, cefotaxime, ceftriaxone and ertapenem. Among novel β-lactam/inhibitor combinations, ceftazidime/avibactam exhibited moderate activity, with 50% of isolates susceptible. All isolates demonstrated resistance to imipenem/cilastatin/relebactam, and all but one to ceftolozane/tazobactam. Four isolates exhibited a multidrug-resistant phenotype (MDR), whereas six were allocated to an extensively drug-resistant phenotype (XDR). OKNV detected three combinations of carbapenemases: OXA-48+NDM (five isolates), OXA-48+VIM (three isolates) and OXA-48+KPC (two isolates). Inter-array testing identified a wide variety of resistance genes for β-lactam antibiotics: <i>bla</i><sub>CTX-M-15</sub>, <i>bla</i><sub>TEM</sub>, <i>bla</i><sub>SHV</sub>, <i>bla</i><sub>OXA-1</sub>, <i>bla</i><sub>OXA-2</sub>, <i>bla</i><sub>OXA-9</sub>, aminoglycosides: <i>aac</i>6, <i>aad</i>, <i>rmt</i>, <i>arm</i> and <i>aph</i>, fluoroquinolones: <i>qnr</i>A, <i>qnr</i>B and <i>qnr</i>S, sulphonamides: <i>sul</i>1 and <i>sul</i>2 and trimethoprim: <i>dfrA5, dfrA7, dfrA14, dfrA17 and dfrA19</i>. <i>mcr</i> genes were reported for the first time in Croatia. This study demonstrated the ability of <i>K. pneumoniae</i> and <i>E. cloacae</i> to acquire various resistance determinants under the selection pressure of antibiotics widely used during the COVID-19 pandemic. The novel inter-array method showed good correlation with OKNV and PCR, although some discrepancies were found.
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spelling doaj.art-935bfb480d424c229b348f10cf1846592023-11-18T02:46:47ZengMDPI AGPathogens2076-08172023-05-0112567710.3390/pathogens12050677Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 PandemicBranka Bedenić0Josefa Luxner1Haris Car2Sanda Sardelić3Maja Bogdan4Dijana Varda-Brkić5Sandra Šuto6Andrea Grisold7Nataša Beader8Gernot Zarfel9Department of Microbiology, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaInstitute for Hygiene, Microbiology and Environmental Medicine, Medical University Graz, 8010 Graz, AustriaZagreb Health School, 10000 Zagreb, CroatiaDepartment of Microbiology, University Hospital Centre Split, 21000 Split, CroatiaDepartment of Microbiology, University Hospital Centre Osijek, 31000 Osijek, CroatiaClinical Department for Clinical and Molecular Microbiology, University Hospital Center Zagreb, 10000 Zagreb, CroatiaDepartment of Microbiology, Andrija Štampar Public Health Institute, 10000 Zagreb, CroatiaInstitute for Hygiene, Microbiology and Environmental Medicine, Medical University Graz, 8010 Graz, AustriaDepartment of Microbiology, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaInstitute for Hygiene, Microbiology and Environmental Medicine, Medical University Graz, 8010 Graz, AustriaResistance to carbapenems in <i>Enterobacterales</i> has become a matter of the highest concern in the last decade. Recently, <i>Enterobacterales</i> harboring multiple carbapenemases were detected in three hospital centers in Croatia and in the outpatient setting, posing a serious therapeutic challenge for clinicians. In this study, we analyzed eight <i>Klebsiella pneumoniae</i> and two <i>Enterobacter cloacae</i> complex isolates with multiple carbapenemases, with regard to antibiotic susceptibility, β-lactamase production and plasmid content. The isolates demonstrated uniform resistance to amoxicillin/clavulanate, piperacillin/tazobactam, cefuroxime, ceftazidime, cefotaxime, ceftriaxone and ertapenem. Among novel β-lactam/inhibitor combinations, ceftazidime/avibactam exhibited moderate activity, with 50% of isolates susceptible. All isolates demonstrated resistance to imipenem/cilastatin/relebactam, and all but one to ceftolozane/tazobactam. Four isolates exhibited a multidrug-resistant phenotype (MDR), whereas six were allocated to an extensively drug-resistant phenotype (XDR). OKNV detected three combinations of carbapenemases: OXA-48+NDM (five isolates), OXA-48+VIM (three isolates) and OXA-48+KPC (two isolates). Inter-array testing identified a wide variety of resistance genes for β-lactam antibiotics: <i>bla</i><sub>CTX-M-15</sub>, <i>bla</i><sub>TEM</sub>, <i>bla</i><sub>SHV</sub>, <i>bla</i><sub>OXA-1</sub>, <i>bla</i><sub>OXA-2</sub>, <i>bla</i><sub>OXA-9</sub>, aminoglycosides: <i>aac</i>6, <i>aad</i>, <i>rmt</i>, <i>arm</i> and <i>aph</i>, fluoroquinolones: <i>qnr</i>A, <i>qnr</i>B and <i>qnr</i>S, sulphonamides: <i>sul</i>1 and <i>sul</i>2 and trimethoprim: <i>dfrA5, dfrA7, dfrA14, dfrA17 and dfrA19</i>. <i>mcr</i> genes were reported for the first time in Croatia. This study demonstrated the ability of <i>K. pneumoniae</i> and <i>E. cloacae</i> to acquire various resistance determinants under the selection pressure of antibiotics widely used during the COVID-19 pandemic. The novel inter-array method showed good correlation with OKNV and PCR, although some discrepancies were found.https://www.mdpi.com/2076-0817/12/5/677Enterobacteralesmultiple carbapenemasesresistanceOXA-48NDMVIM
spellingShingle Branka Bedenić
Josefa Luxner
Haris Car
Sanda Sardelić
Maja Bogdan
Dijana Varda-Brkić
Sandra Šuto
Andrea Grisold
Nataša Beader
Gernot Zarfel
Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic
Pathogens
Enterobacterales
multiple carbapenemases
resistance
OXA-48
NDM
VIM
title Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic
title_full Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic
title_fullStr Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic
title_full_unstemmed Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic
title_short Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic
title_sort emergence and spread of enterobacterales with multiple carbapenemases after covid 19 pandemic
topic Enterobacterales
multiple carbapenemases
resistance
OXA-48
NDM
VIM
url https://www.mdpi.com/2076-0817/12/5/677
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