MSc.
Si Nguyen Thu Mai
Molecular Epidemiology, Oxford University Clinical Research Unit, Ho Chi Minh City
Title: The rise of carbapenem-resistant Klebsiella pneumoniae sequence type 16 in Vietnam
Si-Nguyen Thu Mai1, Lan Phu Huong Nguyen2, Se Eun Park3, Jeon Yeonji3, Thanh Dung Nguyen2, Guy Thwaites1,4, Phuong Thao Huynh2, Ngan Thi Quynh Le2, Quang Minh Ho2, Hao Chung The1,5, Quynh Nguyen1, Vinh Chau1, Anh Hong Pham1, Duy Thanh Pham*1,4
1 Molecular Epidemiology, Oxford University Clinical Research Unit, Ho Chi Minh, Vietnam
2 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Ho Chi Minh, Vietnam
3 International Vaccine Institute, Seoul, South Korea, Seoul, South Korea
4 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
5 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a critical public health threat globally, and understanding the dynamics of specific high-risk lineages is therefore crucial, especially in lower-middle-income countries as Vietnam. Our ongoing genomic study on CRKP during and post-COVID-19 pandemic (2021-present) has recorded a striking increase in the proportion of sequence type 16 (ST16), contrary to the dominance of ST15 as reported in previous years. These emerging CRKP ST16 isolates exhibited extensive drug resistance to commonly used antimicrobials, including 3rd/4th-generation cephalosporins, piperacillin-tazobactam, ceftazidime-avibactam, and colistin. ESBL-encoding gene (blaCTX-M-15) and carbapenemase-encoding genes (blaOXA-48 or blaOXA-181) were detected in all ST16 isolates. Colistin resistance was largely mediated by transposition of IS elements, leading to truncations of mgrB. The blaOXA-48 was identified on a 63-kb IncL plasmid, while blaOXA-181 was on a 51-kb IncX3 plasmid. Among the blaOXA-181-carrying isolates, nearly one-fourth harboured additionally a blaNDM-4 on an 83-kb IncFII(Yp) plasmid. Such co-presence was associated with increased minimum inhibitory concentrations of meropenem and resistance to ceftazidime-avibactam. Notably, the IncFII(Yp) plasmid backbone was found in all blaOXA-181-carrying isolates, regardless of the blaNDM-4 presence. These features demonstrate the genetic plasticity of ST16, enabling its rapid gain and loss of blaNDM-4 , and the development of colistin resistance. Lastly, phylogenetic analyses revealed the country-wide circulation of ST16 variants. Five major phylogroups were found that separated by ß-lactam-tolerance mutations in OmpK35 and OmpK36 porins. Furthermore, Bayesian dating on the phylogenetic tree indicated a recent acquisition of an integrative conjugative element ICEKp12 in one large phylogroup, which provides a virulence yersiniabactin (ybt) locus for the bacteria. Together, our work timely reports the recent surge of the CRKP ST16 that exhibited continuing evolution towards extensive drug resistance and potentially more virulence in Vietnam, demanding immediate attention for enhanced surveillance and mitigation strategies for this critical pathogen.
Biography of the presenting author
Si-Nguyen T. Mai is a Research Assistant of the Molecular Epidemiology Group at Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. She holds an MSc degree in Evolutionary Biology, from the University of Groningen, and a BEng in Biomedical Engineering from the International University – Vietnam National University Ho Chi Minh City. Her research interests and experience are in microbial ecology and evolution in infections and antimicrobial resistance.
Presenting author details
Full name: Si-Nguyen Thu Mai
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Email: nguyenmts@oucru.org
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Google Scholar: https://scholar.google.com/citations?user=uD7Ww4sAAAAJ&hl=en
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ORCID: https://orcid.org/0000-0003-1269-9683
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Session name/ number: Antimicrobial resistance and treatment
Category: Oral presentation