Plasmid-mediated quinolone resistance determinants in Enterobacteriaceae isolated in Ho Chi Minh City, Vietnam

Fluoroquinolones are amongst the most effective antimicrobials used to treat infectious diseases caused by members of the Enterobacteriaceae. The rapid spread of fluoroquinolone resistant Enterobacteriaceae threatens the future effectiveness of this widely used group of antimicrobial compounds. Fluoroquinolone resistance in Enterobacteriaceae in Vietnam highlights an approaching crisis in antimicrobial therapy of Enterobacteriaceae infections as fluoroquinolone resistant infections may require expensive alternative treatments. Furthermore, a lack of alternative drugs for treating fluoroquinolone resistant bacteria also contributes to the difficulty in treating such infections. The aim of this study was to investigate the prevalence and mechanisms of fluoroquinolone resistance in commensal Enterobacteriaceae isolated from two different populations resident in Ho Chi Minh City; hospitalized patients and healthy volunteers. I investigated the prevalence of mutations in the DNA gyrase and the topoisomerase gene, the target of the fluoroquinolones and the main resistance mechanisms in Enterobacteriaceae. Additionally, I investigated the spectrum of plasmid-mediated quinolone resistance (PMQR) determinants, a more contemporary mechanism of fluoroquinolone resistance. By using whole plasmid sequencing, bioinformatics and a miniaturized DNA nanoarray, an association of PMQR determinants with other antimicrobial resistance genes including blaLAP-2, which confers resistance to β-lactam antimicrobials, was found. Moreover, diverse patterns of antimicrobial resistance between isolates from hospital and community populations were revealed. An increase in the quantity of PMQR determinants isolated from rectal swabs of children treated with antimicrobials was also demonstrated using a gene specific real-time PCR. I surmise that variety antimicrobial classes might contribute to an increase in copy number and co-selection of PMQR determinants in Ho Chi Minh City. Fluoroquinolone resistance in Enterobacteriaceae has increased over time and this class of antimicrobial is still commonly used to treat infection caused by such organisms. Understanding fluoroquinolone resistance mechanisms and their relationship to other antimicrobial resistance mechanisms in Enterobacteriaceae should play an important role in the control of the spread of antimicrobial resistance genes and aid treatment strategies for clinicians in Vietnam.This thesis is not currently available via ORA