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Colonization dynamics of extended-spectrum beta-lactamase-producing Enterobacterales in the gut of Malawian adults

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  • Joseph M Lewis
  • Madalitso Mphasa
  • Rachel Banda
  • Mathew A Beale
  • Eva Heinz
  • Jane Mallewa
  • Christopher Jewell
  • Brian Faragher
  • Nicholas R Thomson
  • Nicholas A Feasey
<mark>Journal publication date</mark>31/10/2022
<mark>Journal</mark>Nature Microbiology
Issue number10
Number of pages12
Pages (from-to)1593-1604
Publication StatusPublished
Early online date5/09/22
<mark>Original language</mark>English


Drug-resistant bacteria of the order Enterobacterales which produce extended-spectrum beta-lactamase enzymes (ESBL-Enterobacterales, ESBL-E) are global priority pathogens. Antimicrobial stewardship interventions proposed to curb their spread include shorter courses of antimicrobials to reduce selection pressure but individual-level acquisition and selection dynamics are poorly understood. We sampled stool of 425 adults (aged 16-76 years) in Blantyre, Malawi, over 6 months and used multistate modelling and whole-genome sequencing to understand colonization dynamics of ESBL-E. Models suggest a prolonged effect of antimicrobials such that truncating an antimicrobial course at 2 days has a limited effect in reducing colonization. Genomic analysis shows largely indistinguishable diversity of healthcare-associated and community-acquired isolates, hence some apparent acquisition of ESBL-E during hospitalization may instead represent selection from a patient's microbiota by antimicrobial exposure. Our approach could help guide stewardship protocols; interventions that aim to review and truncate courses of unneeded antimicrobials may be of limited use in preventing ESBL-E colonization.