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Extremely drug-resistant NDM-9-producing ST147 Klebsiella pneumoniae causing infections in Italy, May 2020.

ABSTRACT: A large outbreak of New Delhi metallo-beta-lactamase (NDM)-1-producing Klebsiella pneumoniae sequence type (ST) 147 occurred in Tuscany, Italy in 2018-2019. In 2020, ST147 NDM-9-producing K. pneumoniae were detected at the University Hospital of Pisa, Tuscany, in two critically ill patients; one developed bacteraemia. Genomic and phylogenetic analyses suggest relatedness of 2018-2019 and 2020 strains, with a change from NDM-1 to NDM-9 in the latter and evolution by colistin, tigecycline and fosfomycin resistance acquisition.

SUBMITTER: Falcone M

PROVIDER: S-EPMC7716400 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Extremely drug-resistant NDM-9-producing ST147 Klebsiella pneumoniae causing infections in Italy, May 2020.

Falcone Marco M Giordano Cesira C Barnini Simona S Tiseo Giusy G Leonildi Alessandro A Malacarne Paolo P Menichetti Francesco F Carattoli Alessandra A

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 20201201 48

A large outbreak of New Delhi metallo-beta-lactamase (NDM)-1-producing Klebsiella pneumoniae sequence type (ST) 147 occurred in Tuscany, Italy in 2018-2019. In 2020, ST147 NDM-9-producing K. pneumoniae were detected at the University Hospital of Pisa, Tuscany, in two critically ill patients; one developed bacteraemia. Genomic and phylogenetic analyses suggest relatedness of 2018-2019 and 2020 strains, with a change from NDM-1 to NDM-9 in the latter and evolution by colistin, tigecy ...[more]

PMID: 33272354

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Project description:Klebsiella pneumoniae is a major cause of neonatal sepsis. Hypervirulent Klebsiella pneumoniae (hvKP) that cause invasive infections and/or carbapenem-resistant hvKP (CR-hvKP) limit therapeutic options. Such strains causing neonatal sepsis have rarely been studied. Characterization of neonatal septicemic hvKP/CR-hvKP strains in terms of resistance and virulence was carried out. Antibiotic susceptibility, molecular characterization, evaluation of clonality, in vitro virulence, and transmissibility of carbapenemase genes were evaluated. Whole-genome sequencing (WGS) and mouse lethality assays were performed on strains harboring pLVPK-associated markers. About one-fourth (26%, 28/107) of the studied strains, leading to mortality in 39% (11/28) of the infected neonates, were categorized as hvKP. hvKP-K2 was the prevalent pathotype (64.2%, 18/28), but K54 and K57 were also identified. Most strains were clonally diverse belonging to 12 sequence types, of which ST14 was most common. Majority of hvKPs possessed virulence determinants, strong biofilm-forming, and high serum resistance ability. Nine hvKPs were carbapenem-resistant, harboring blaNDM-1/blaNDM-5 on conjugative plasmids of different replicon types. Two NDM-1-producing high-risk clones, ST11 and ST15, had pLVPK-associated markers (rmpA, rmpA2, iroBCDEN, iucABCDiutA, and peg-344), of which one co-transferred the markers along with blaNDM-1. The 2 strains revealed high inter-genomic resemblance with the other hvKP reference genomes, and were lethal in mouse model. To the best of our knowledge, this study is the first to report on the NDM-1-producing hvKP ST11-K2 and ST15-K54 strains causing fatal neonatal sepsis. The presence of pLVPK-associated markers and blaNDM-1 in high-risk clones, and the co-transmission of these genes via conjugation calls for surveillance of these strains. IMPORTANCE Klebsiella pneumoniae is a leading cause of sepsis in newborns and adults. Among the 2 major pathotypes of K. pneumoniae, classical (cKP) and hypervirulent (hvKP), hvKP causes community-acquired severe fatal invasive infections in even healthy individuals, as it possesses several virulence factors. The lack of comprehensive studies on neonatal septicemic hvKPs prompted this work. Nearly 26% diverse hvKP strains were recovered possessing several resistance and virulence determinants. The majority of them exhibited strong biofilm-forming and high serum resistance ability. Nine of these strains were also carbapenem (last-resort antibiotic)-resistant, of which 2 high-risk clones (ST11-K2 and ST15-K54) harbored markers (pLVPK) noted for their virulence, and were lethal in the mouse model. Genome-level characterization of the high-risk clones showed resemblance with the other hvKP reference genomes. The presence of transmissible carbapenem-resistant gene, blaNDM, along with pLVPK-markers calls for vigilance, as most clinical microbiology laboratories do not test for them.

Project description:Klebsiella pneumoniae is a significant infectious pathogen that causes bloodstream infections. This study aimed to genetically characterize a novel sequence type 4523 (ST4523) multidrug-resistant (MDR) K. pneumoniae strain recovered from the blood of a 79-year-old Chinese female patient with severe pneumonia and chronic obstructive pulmonary disease who ultimately died of the infection. The susceptibility testing results showed that strain 18SHX180 is nonsusceptible to cephalosporin, carbapenems, combinations of β-lactam and β-lactamase inhibitors, levofloxacin, and colistin and is only susceptible to amikacin. The phylogenetic structure showed that strain 18SHX180 belongs to a novel sequence type, ST4523, and capsule serotype K111. ST4523 is closely related to ST11, the most dominant clone of clinical carbapenem-resistant K. pneumoniae in China. ST4523 has 2 single-base variants in mdh and phoE. 18SHX180 showed medium virulence in Galleria mellonella and a mouse intraperitoneal infection model. PacBio Sequel and Illumina sequencing were performed to analyze the genetic characterization of 18SHX180, which contains 2 plasmids (pSHX180-NDM5 and pSHX180-1). pSHX180-NDM5 exhibits 86% coverage and 100% identity with 3 blaNDM-5-carrying plasmids and contains an additional region coding for the frmRAB operon, which permits bacteria to sense and detoxify formaldehyde. pSHX180-1 is responsible for the MDR phenotype: it carries 11 categories of genes for antimicrobial resistance [aadA16, aph(3″)-Ib, aph(6)-Id, blaSHV-182, blaTEM-1A, qacE, aac(6')-Ib-cr, mph(A), floR, qnrB6, arr-3, sul, sul2], all of which are associated with transposons and integrons located in three accessory resistance regions. The novel ST4523 K. pneumoniae strain could threaten the control of antimicrobial resistance, and its discovery calls attention to the genetic evolution of bacteria. IMPORTANCE Klebsiella pneumoniae is a significant infectious pathogen causing bloodstream infections. Due to the dissemination of carbapenemase genes, the incidence of carbapenem-resistant K. pneumoniae (CRKP) has increased, with high morbidity and mortality rates in immunocompromised patients. Here, we reported a novel ST4523 blaNDM-5-bearing CRKP strain initially recovered from a 79-year-old female who died of both a lower respiratory tract infection and bloodstream infection. We also describe the genetic and phenotypic characteristics of this strain. This study provides important insights into the genetic evolution of ST11 K. pneumoniae.

Dataset Information

Extremely drug-resistant NDM-9-producing ST147 Klebsiella pneumoniae causing infections in Italy, May 2020.

Publications

Extremely drug-resistant NDM-9-producing ST147 <i>Klebsiella pneumoniae</i> causing infections in Italy, May 2020.

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