2020•Emerging infectious diseasesOpen access

Carbapenem Resistance Conferred by OXA-48 in K2-ST86 Hypervirulent Klebsiella pneumoniae, France

Racha Beyrouthy, Guillaume Dalmasso, A. Birer, Frédéric Robin, Richard Bonnet

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Abstract

K lebsiella pneumoniae is a threat to human health because of the emergence of hypervirulent K. pneumoniae, which has caused severe community-acquired infections, and classical multidrug-resistant K. pneumoniae involved in hospital outbreaks (1).Classical K. pneumoniae generally lacks the virulence genes associated with invasive diseases (1) and belongs to successful clonal groups, such as sequence type (ST) 11 and ST258 (2).Most hypervirulent K. pneumoniae isolates, which are mainly found in Asia (3,4), belong to the K1 and K2 capsular serotypes and are restricted to clonal complexes different from classical multidrug-resistant K. pneumoniae groups, such as K1-ST23, the most prevalent group (2).They rarely harbor acquired antimicrobial resistance genes but have virulence loci and a hypermucoviscous phenotype (5).We describe 2 hypermucoviscous K2-ST86 K. pneumoniae (positive string test) resistant to carbapenems isolated in northern and southern France. The StudyIn 2017, we recovered the Kpn154 strain from the urine of a 35-year-old man with community-acquired urinary tract infection.He had fever (39°C) before local symptoms suggesting urinary tract infection caused by bacteremic spread, which was successfully treated with intravenous ceftriaxone.A second strain, Kpn2166, was hospital-acquired and recovered from the feces of a 70-year-old man in the intensive care unit of the hospital at which the 35-year-old patient was seem.Neither patient reported travel during the past 4 years.Both strains were resistant to all penicillins and their combinations with β-lactamase inhibitors, and to carbapenems according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) guidelines (https://www.eucast.org)(Table).In addition, Kpn2166 was resistant to the third-generation cephalosporins, quinolones and tigecycline.We obtained the isolates' whole-genome sequence by hybrid de novo assembly of short and long reads generated with technologies from Illumina (https://www.illumina.com)and Oxford Nanopore (https://nanoporetech.com;European Nucleotide Archive at EMBL-EBI under accession no.PRJEB34867).We typed the isolates as K2-ST86 from whole-genome sequencing using the Institut Pasteur multilocus sequence typing scheme (https://bigsdb.pasteur.fr)and Kleborate (6).Kpn154 harbored carbapenemase-encoding gene bla oxa-48 and Kpn2166 the extended-spectrum β-lactamase-encoding gene bla CTX-M-15 as the only acquired β-lactamase-encoding genes.CTX-M-15 associated with the truncation of the outer membrane protein OmpK36 caused by 11-bp deletion Carbapenem Resistance Conferred by OXA-48 in K2-ST86 Hypervirulent Klebsiella pneumoniae, France

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K lebsiella pneumoniae is a threat to human health because of the emergence of hypervirulent K. pneumoniae, which has caused severe community-acquired infections, and classical multidrug-resistant K. pneumoniae involved in hospital outbreaks (1).Classical K. pneumoniae generally lacks the virulence genes associated with invasive diseases (1) and belongs to successful clonal groups, such as sequence type (ST) 11 and ST258 (2).Most hypervirulent K. pneumoniae isolates, which are mainly found in Asia (3,4), belong to the K1 and K2 capsular serotypes and are restricted to clonal complexes different from classical multidrug-resistant K. pneumoniae groups, such as K1-ST23, the most prevalent group (2).They rarely harbor acquired antimicrobial resistance genes but have virulence loci and a hypermucoviscous phenotype (5).We describe 2 hypermucoviscous K2-ST86 K. pneumoniae (positive string test) resistant to carbapenems isolated in northern and southern France. The StudyIn 2017, we recovered the Kpn154 strain from the urine of a 35-year-old man with community-acquired urinary tract infection.He had fever (39°C) before local symptoms suggesting urinary tract infection caused by bacteremic spread, which was successfully treated with intravenous ceftriaxone.A second strain, Kpn2166, was hospital-acquired and recovered from the feces of a 70-year-old man in the intensive care unit of the hospital at which the 35-year-old patient was seem.Neither patient reported travel during the past 4 years.Both strains were resistant to all penicillins and their combinations with β-lactamase inhibitors, and to carbapenems according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) guidelines (https://www.eucast.org)(Table).In addition, Kpn2166 was resistant to the third-generation cephalosporins, quinolones and tigecycline.We obtained the isolates' whole-genome sequence by hybrid de novo assembly of short and long reads generated with technologies from Illumina (https://www.illumina.com)and Oxford Nanopore (https://nanoporetech.com;European Nucleotide Archive at EMBL-EBI under accession no.PRJEB34867).We typed the isolates as K2-ST86 from whole-genome sequencing using the Institut Pasteur multilocus sequence typing scheme (https://bigsdb.pasteur.fr)and Kleborate (6).Kpn154 harbored carbapenemase-encoding gene bla oxa-48 and Kpn2166 the extended-spectrum β-lactamase-encoding gene bla CTX-M-15 as the only acquired β-lactamase-encoding genes.CTX-M-15 associated with the truncation of the outer membrane protein OmpK36 caused by 11-bp deletion Carbapenem Resistance Conferred by OXA-48 in K2-ST86 Hypervirulent Klebsiella pneumoniae, France

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Available abstract

K lebsiella pneumoniae is a threat to human health because of the emergence of hypervirulent K. pneumoniae, which has caused severe community-acquired infections, and classical multidrug-resistant K. pneumoniae involved in hospital outbreaks (1).Classical K. pneumoniae generally lacks the virulence genes associated with invasive diseases (1) and belongs to successful clonal groups, such as sequence type (ST) 11 and ST258 (2).Most hypervirulent K. pneumoniae isolates, which are mainly found in Asia (3,4), belong to the K1 and K2 capsular serotypes and are restricted to clonal complexes different from classical multidrug-resistant K. pneumoniae groups, such as K1-ST23, the most prevalent group (2).They rarely harbor acquired antimicrobial resistance genes but have virulence loci and a hypermucoviscous phenotype (5).We describe 2 hypermucoviscous K2-ST86 K. pneumoniae (positive string test) resistant to carbapenems isolated in northern and southern France. The StudyIn 2017, we recovered the Kpn154 strain from the urine of a 35-year-old man with community-acquired urinary tract infection.He had fever (39°C) before local symptoms suggesting urinary tract infection caused by bacteremic spread, which was successfully treated with intravenous ceftriaxone.A second strain, Kpn2166, was hospital-acquired and recovered from the feces of a 70-year-old man in the intensive care unit of the hospital at which the 35-year-old patient was seem.Neither patient reported travel during the past 4 years.Both strains were resistant to all penicillins and their combinations with β-lactamase inhibitors, and to carbapenems according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) guidelines (https://www.eucast.org)(Table).In addition, Kpn2166 was resistant to the third-generation cephalosporins, quinolones and tigecycline.We obtained the isolates' whole-genome sequence by hybrid de novo assembly of short and long reads generated with technologies from Illumina (https://www.illumina.com)and Oxford Nanopore (https://nanoporetech.com;European Nucleotide Archive at EMBL-EBI under accession no.PRJEB34867).We typed the isolates as K2-ST86 from whole-genome sequencing using the Institut Pasteur multilocus sequence typing scheme (https://bigsdb.pasteur.fr)and Kleborate (6).Kpn154 harbored carbapenemase-encoding gene bla oxa-48 and Kpn2166 the extended-spectrum β-lactamase-encoding gene bla CTX-M-15 as the only acquired β-lactamase-encoding genes.CTX-M-15 associated with the truncation of the outer membrane protein OmpK36 caused by 11-bp deletion Carbapenem Resistance Conferred by OXA-48 in K2-ST86 Hypervirulent Klebsiella pneumoniae, France

Key concepts: Klebsiella pneumoniae, Klebsiella infections, Microbiology, Biology, Carbapenem, Klebsiella, Virology, Antibiotic resistance

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