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Genome Med. 2020 Jan 16;12(1):11. doi: 10.1186/s13073-019-0706-y.

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

Author information

1
Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria, 3004, Australia.
2
Hospital of Tropical Diseases, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
3
The Hospital of Tropical Diseases, Ho Chi Minh City, Vietnam.
4
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.
5
Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
6
London School of Hygiene and Tropical Medicine, London, UK.
7
Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
8
Patan Academy of Health Sciences, Oxford University Clinical Research Unit, Kathmandu, Nepal.
9
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, 63110, Thailand.
10
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
11
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.
12
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
13
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK. sgb47@medschl.cam.ac.uk.

Abstract

BACKGROUND:

Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum 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 K-loci. 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.

KEYWORDS:

Bloodstream infection; Capsule types; Genomic surveillance; Hypervirulent; Klebsiella pneumoniae; MDR

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