Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages.


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
01 05 2019
Historique:
received: 02 08 2018
revised: 27 12 2018
accepted: 08 01 2019
pubmed: 20 2 2019
medline: 23 2 2021
entrez: 20 2 2019
Statut: ppublish

Résumé

ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations.

Identifiants

pubmed: 30778540
pii: 5333166
doi: 10.1093/jac/dkz032
pmc: PMC6477993
doi:

Substances chimiques

Anti-Bacterial Agents 0
beta-Lactamases EC 3.5.2.6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1223-1232

Subventions

Organisme : Wellcome Trust
ID : 098051
Pays : United Kingdom

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

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Auteurs

Patrick Musicha (P)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Chisomo L Msefula (CL)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
College of Medicine, University of Malawi, Blantyre, Malawi.

Alison E Mather (AE)

Quadram Institute Bioscience, Norwich, UK.

Chrispin Chaguza (C)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Wellcome Sanger Institute, Hinxton, Cambridge, UK.

Amy K Cain (AK)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Liverpool School of Tropical Medicine, Liverpool, UK.

Chikondi Peno (C)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Teemu Kallonen (T)

Wellcome Sanger Institute, Hinxton, Cambridge, UK.

Margaret Khonga (M)

College of Medicine, University of Malawi, Blantyre, Malawi.

Brigitte Denis (B)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Katherine J Gray (KJ)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Robert S Heyderman (RS)

Division of Infection and Immunity, University College London, London, UK.

Nicholas R Thomson (NR)

Quadram Institute Bioscience, Norwich, UK.
London School of Tropical Medicine, London, UK.

Dean B Everett (DB)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
University of Edinburgh, Edinburgh, UK.

Nicholas A Feasey (NA)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Liverpool School of Tropical Medicine, Liverpool, UK.

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Classifications MeSH