Identification of a Carbapenemase-Producing Hypervirulent Klebsiella pneumoniae Isolate in the United States

Karlsson, Maria; Stanton, Richard A.; Ansari, Uzma; McAllister, Gillian; Chan, Monica; Sula, Erisa; Grass, Julian; Duffy, Nadezhda; Anacker, Melissa; Witwer, Medora; Rasheed, J. Kamile; Elkins, Christopher A.; Halpin, Alison Laufer

doi:10.1128/aac.00519-19

Cited by 66 publications

(55 citation statements)

References 34 publications

(25 reference statements)

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“…This strain encoded two plasmids, the first being a large hybrid virulence and resistance plasmid that encoded carbapenem resistance via bla KPC-2 , similar to other hybrid plasmids reported in China [158,159]. The second plasmid, which encodes bla KPC-2 and bla TEM-1A , is homologous to plasmids reported to be responsible for the dissemination of carbapenem resistance amongst Enterobacteriaceae [153]. Another example of an hvKp strain becoming multidrug resistant is strain 11492, isolated in China.…”

Section: Convergence Of Virulence and Antibiotic Resistancesupporting

confidence: 57%

“…A survey of global K. pneumoniae isolates detected antimicrobial resistance genes in multiple K2 ST43 isolates . A recent example includes a K1 ST23 hvKp isolated in the United States, which appeared to be asymptomatically colonizing a patient . This strain encoded two plasmids, the first being a large hybrid virulence and resistance plasmid that encoded carbapenem resistance via bla KPC‐2 , similar to other hybrid plasmids reported in China .…”

Section: Convergence Of Virulence and Antibiotic Resistancementioning

confidence: 70%

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Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

2019

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Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a concerning global pathogen. hvKp is more virulent than classical K. pneumoniae (cKp) and capable of causing community‐acquired infections, often in healthy individuals. hvKp is carried in the gastrointestinal tract, which contributes to its spread in the community and healthcare settings. First recognized in Asia, hvKp arose as a leading cause of pyogenic liver abscesses. In the decades since, hvKp has spread globally and causes a variety of infections. In addition to liver abscesses, hvKp is distinct from cKp in its ability to metastasize to distant sites, including most commonly the eye, lung and central nervous system (CNS). hvKp has also been implicated in primary extrahepatic infections including bacteremia, pneumonia and soft tissue infections. The genetic determinants of hypervirulence are often found on large virulence plasmids as well as chromosomal mobile genetic elements which can be used as biomarkers to distinguish hvKp from cKp clinical isolates. These distinct virulence determinants of hvKp include up to four siderophore systems for iron acquisition, increased capsule production, K1 and K2 capsule types, and the colibactin toxin. Additionally, hvKp strains demonstrate hypermucoviscosity, a phenotypic description of hvKp in laboratory conditions that has become a distinguishing feature of many hypervirulent isolates. Alarmingly, multidrug‐resistant hypervirulent strains have emerged, creating a new challenge in combating this already dangerous pathogen.

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Section: Convergence Of Virulence and Antibiotic Resistancesupporting

confidence: 57%

Section: Convergence Of Virulence and Antibiotic Resistancementioning

confidence: 70%

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

2019

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“…Inversely, the carbapenemase-producing isolate Kpn154 results from the transformation of K2-ST86 hypervirulent K. pneumoniae by plasmid encoding carbapenemase OXA-48, the most prevalent carbapenemase in France. Similar events occurred with the KPC-2 K2-ST86 isolate recently reported in Canada (13) and a few KPC-2 and NDM K1-ST23 cases documented in China and recently in the United States and United Kingdom (5,14,15). The combination of multidrug resistance and enhanced virulence has the potential to trigger the next clinical crisis and cause severe and untreatable infections in previously healthy persons.…”

Section: Discussionsupporting

confidence: 81%

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

Beyrouthy¹,

Dalmasso²,

Birer³

et al. 2020

Emerg. Infect. Dis.

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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 Study In 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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“…To date the majority of hypervirulent K. pneumoniae have remained susceptible to antimicrobials [38,46] (except ampicillin). However, the last few years have seen increasing reports of "convergent" K. pneumoniae that are both hypervirulent (defined as strains carrying the iuc aerobactin locus) and MDR ESBL/CP either due to acquisition of an MDR plasmid by a hypervirulent strain [47][48][49][50][51] or by acquisition of a virulence plasmid by an MDR strain [49,[52][53][54][55][56]. The majority of these reports represent sporadic isolations.…”

Section: Introductionmentioning

confidence: 99%

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

et al. 2020

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Background: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extendedspectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. Methods: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. Results: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 Kloci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae.Conclusions: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.

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Identification of a Carbapenemase-Producing Hypervirulent Klebsiella pneumoniae Isolate in the United States

Cited by 66 publications

References 34 publications

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

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

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

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