University of Cambridge > > Bradford Hill Seminars > Recent insights into drug resistant Shigella: a major contributor to the global diarrhoeal disease burden

Recent insights into drug resistant Shigella: a major contributor to the global diarrhoeal disease burden

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Diarrhoea is a major global health problem, and recent studies have confirmed a group of bacteria known as Shigella are a major contributor to this burden. People living in, or travelling to, areas with poor sanitation are at increased risk of becoming infected. Infants and toddlers, the elderly, and ill people are susceptible to the most severe symptoms, including serious complications such as dehydration.

Fluoroquinolone antibiotics remain the recommended therapy for shigellosis, despite the sporadic detection of fluoroquinolone-resistant Shigella in Asia in the early 2000s and subsequent global spread of ciprofloxacin-resistant Shigella sonnei from 2010. The potential for ciprofloxacin-resistant Shigella sonnei to develop resistance to alternative drugs may further limit future treatment options. Antimicrobial resistance is therefore a major emerging threat in treating Shigella.

My research aimed to understand the evolution of new antimicrobial resistant (AMR) S. sonnei variants in Vietnam. We found that ciprofloxacin-resistant Shigella sonnei displaced the existing non-resistant form while rapidly acquiring additional resistance to multiple alternative antimicrobial classes. We identified several independent acquisitions of XDR /MDR-inducing plasmids, likely facilitated by horizontal transfer from commensals in the human gut. By examining commensal E. coli in Shigella-infected and healthy children, we identified an extensive array of AMR genes and plasmids, including an identical MDR plasmid isolated from both S. sonnei and E. coli in the gut of a single child. We also found that the use of antimicrobial drugs may impact plasmid transfer between commensal E. coli and S. sonnei. These results suggest that in a setting with high antimicrobial drug use and a high prevalence of AMR commensals ciprofloxacin-resistant Shigella sonnei may develop pan-resistance by adherence to outdated international treatment guidelines.

This seminar will be chaired by Daniela De Angelis, Deputy Director of the MRC Biostatistics Unit, University of Cambridge.

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