Complete Genome Sequence of a Multidrug-Resistant Klebsiella pneumoniae Strain Carrying blaOXA181 and blaKPC-125 Carbapenemase

Gaibani, Paolo; Amadesi, Stefano; Lazzarotto, Tiziana; Ambretti, Simone

doi:10.1089/mdr.2022.0143

Cited by 1 publication

(5 citation statements)

References 26 publications

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“…Our findings suggest that the resistance to meropenem/vaborbactam and imipenem/relebactam has been associated with the production of OXA-181 carbapenemase, which is unaffected by vaborbactam and relebactam inhibitors, while resistance to ceftazidime/avibactam has probably been associated with mutations within the KPC-3 carbapenemase due to the structural modifications occurring in the Ω-loop. 5 , 15 In addition, all KPC-producing K. pneumoniae isolates included in this study showed high MICs of cefiderocol, thus indicating that the co-production of KPC and OXA-181 carbapenemase and disruption of OmpK35 and mutated OmpK36 (i.e. GD insertion at aa 134–135) porins associated with the co-production of different antimicrobial resistance determinants to β-lactams (i.e.…”

Section: Discussionmentioning

confidence: 82%

“…WGS was performed by the Illumina iSeq 100 platform (iSeq Reagent Kit v2, Illumina, San Diego, USA) using iSeq Reagent kit v2 with 2 × 150 paired-end reads after Illumina DNA Prep paired-end library preparation. 15 , 16 …”

Section: Methodsmentioning

confidence: 99%

“…ST, plasmid replicon type and antimicrobial resistance genes were investigated as previously described. 15 , 16 Sequence variation in genes encoding for the major non-selective porins OmpK35 and OmpK36, and the bla KPC-3 carbapenemase gene was evaluated by aligning amino acid sequence against reference genes as previously described. 15 , 16 Phylogenetic analysis based on core-genome SNPs was performed as previously described.…”

Section: Methodsmentioning

confidence: 99%

“… 15 , 16 Sequence variation in genes encoding for the major non-selective porins OmpK35 and OmpK36, and the bla KPC-3 carbapenemase gene was evaluated by aligning amino acid sequence against reference genes as previously described. 15 , 16 Phylogenetic analysis based on core-genome SNPs was performed as previously described. 15 , 16 A phylogenetic tree was generated in order to compare the strains included in this study with a set of strains isolated at our facility using strain 101BO (accession no.…”

Section: Methodsmentioning

confidence: 99%

“… 15 , 16 Phylogenetic analysis based on core-genome SNPs was performed as previously described. 15 , 16 A phylogenetic tree was generated in order to compare the strains included in this study with a set of strains isolated at our facility using strain 101BO (accession no. CCEY01000001) as a reference.…”

Section: Methodsmentioning

confidence: 99%

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Clonal dissemination of Klebsiella pneumoniae resistant to cefiderocol, ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam co-producing KPC and OXA-181 carbapenemase

Bovo,

Amadesi,

Palombo

et al. 2023

JAC-Antimicrobial Resistance

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Objectives Herein, we describe the epidemiology of carbapenemase-producing Enterobacterales (CPE) before and during the COVID-19 pandemic. Also, we report the emergence of an outbreak of Klebsiella pneumoniae strains co-producing KPC and OXA-181 carbapenemase, resistant to novel β-lactam/β-lactamase inhibitors (βL-βLICs) and cefiderocol. Methods CPE were collected during a period of 3 years from 2019 to 2021. Antimicrobial susceptibility testing for novel βL-βLICs and cefiderocol was performed by MIC test strips and microdilution with iron-depleted broth. WGS was performed on 10 selected isolates using the Illumina platform, and resistome analysis was carried out by a web-based pipeline. Results Between January 2019 and December 2021, we collected 1430 carbapenemase producers from 957 patients with infections due to CPE. KPC was the most common carbapenemase, followed by VIM, OXA-48 and NDM. During 2021, we identified 78 K. pneumoniae co-producing KPC and OXA-181 carbapenemases in 60 patients, resistant to meropenem/vaborbactam and imipenem/relebactam. Resistance to ceftazidime/avibactam and cefiderocol was observed respectively in 7 and 8 out of the 10 sequenced K. pneumoniae. Genome analysis showed that all isolates were clonally related, shared a common porin and plasmid content, and carried blaOXA-181 and blaKPC carbapenemases. Specifically, 4 out of 10 isolates carried blaKPC-3, while 6 harboured mutated blaKPC. Of note, KPC producers resistant to ceftazidime/avibactam and harbouring mutated blaKPC exhibited higher MICs of cefiderocol (median MIC 16 mg/L, IQR 16–16) than strains harbouring WT blaKPC-3 (cefiderocol 9 mg/L, IQR 1.5–16). Conclusions Our results highlight the need for continuous monitoring of CPE to limit widespread MDR pathogens carrying multiple mechanisms conferring resistance to novel antimicrobial molecules.

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Section: Discussionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%