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A genomic approach to understanding the molecular epidemiology and clinical burden of multi-drug resistant Enterobacterale Infections in Bangladesh

Farzana, Refath 2020. A genomic approach to understanding the molecular epidemiology and clinical burden of multi-drug resistant Enterobacterale Infections in Bangladesh. PhD Thesis, Cardiff University.
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Abstract

This PhD was the first comprehensive study in South-Asia, investigating epidemiology of AMR in a Bangladeshi health setting by aligning demographic, clinical, and genomic data. Carbapenem-resistant Enterobacterales (CRE) from clinical specimens were 11.1% (210/1893) and carbapenem-sensitive Enterobacterales (CSE) were 22.8% (433/1893). CRE was associated with age (6-25 years), gender, burn unit and ICU patients. Additionally, with patients given levofloxacin, amikacin, clindamycin, and meropenem during hospital stay (p<0.05). CRE cases were associated with allcause in-hospital 30-days mortality (27.8%) than CSE (13.5%) (p<0.05). Clinical CRE clustered in particular clonal types compared to CSE e.g. ST167, ST448, ST8346, ST405, and ST648 in E. coli, ST16; and ST231, ST11, ST515, and ST23 in K. pneumoniae (p<0.05). CRE clades were associated with direct clonal transmission in putative outbreak clusters (contained isolates of 0-2 SNPs differences), designated as KP5 (K. pneumoniae ST23), KP1 (K. pneumoniae ST15), EC9 (E. coli ST648), and Eco1 (E. cloacae ST113). Plasmid-mediated horizontal transfer of CRE was linked mostly linked to IncFII and IncX3. CRE faecal carriage was 34.8% (244/700) and significantly higher among inpatients (53.8%) than the outpatients (12%) (p<0.05). The clinical and colonisation studies were undertaken about a year apart; however, clusters were found across clinical and faecal isolates (≤20 SNP); these were, EC4 (E. coli ST8346), EC6 (E. coli ST405), EC7 (E. coli ST5954), KP1 (K. pneumoniae ST15), and Eco1 (E. cloacae ST113). Additionally, this PhD describes outbreaks at Dhaka Medical College Hospital e.g. an MDR Klebsiella variicola clone (ST771) in neonatal unit from October 2016 to January 2017, associated with high mortality (54.5%), and by Burkholderia cepacia ST1578 from burn sepsis cases. This study reported the first human-associated mobile colistin resistance in Bangladesh (mcr-1 in faecal colonisation and mcr-8 in clinical infections). Data derived from this study indicate an urgent need of antibiotic stewardship program and standard infection control policy in Bangladeshi hospitals.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 22 April 2021
Last Modified: 22 Apr 2021 09:43
URI: http://orca.cardiff.ac.uk/id/eprint/140464

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