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

Musicha, Patrick, Msefula, Chisomo L, Mather, Alison E, Chaguza, Chrispin, Cain, Amy K, Peno, Chikondi, Kallonen, Teemu, Khonga, Margaret, Denis, Brigitte, Gray, Katherine J, Heyderman, Robert S, Thomson, Nicholas R, Everett, Dean B and Feasey, Nicholas ORCID: https://orcid.org/0000-0003-4041-1405 (2019) 'Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages.'. The Journal of Antimicrobial Chemotherapy, Vol 74, Issue 5, pp. 1223-1232.

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Abstract

OBJECTIVES
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics WA Public Health > WA 105 Epidemiology WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 260 Enterobacteriaceae and other enteric infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/jac/dkz032
Depositing User:	Stacy Murtagh
Date Deposited:	26 Feb 2019 10:38
Last Modified:	31 May 2019 14:26
URI:	https://archive.lstmed.ac.uk/id/eprint/10230

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