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

Lewis, Joseph M. and Mphasa, Madalitso and Banda, Rachel and Beale, Mathew A. and Heinz, Eva and Mallewa, Jane and Jewell, Christopher and Faragher, Brian and Thomson, Nicholas R. and Feasey, Nicholas A. (2022) Colonization dynamics of extended-spectrum beta-lactamase-producing Enterobacterales in the gut of Malawian adults. Nature microbiology, 7 (10). pp. 1593-1604. ISSN 2058-5276 (https://doi.org/10.1038/s41564-022-01216-7)

[thumbnail of Lewis-etal-2022-Colonization-dynamics-of-extended-spectrum-beta-lactamase-producing-Enterobacterales]
Preview
 Text. Filename: Lewis-etal-2022-Colonization-dynamics-of-extended-spectrum-beta-lactamase-producing-Enterobacterales.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo
Download (7MB)| Preview

Abstract

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.

ORCID iDs

Lewis, Joseph M., Mphasa, Madalitso, Banda, Rachel, Beale, Mathew A., Heinz, Eva ORCID logoORCID: https://orcid.org/0000-0003-4413-3756, Mallewa, Jane, Jewell, Christopher, Faragher, Brian, Thomson, Nicholas R. and Feasey, Nicholas A.;
CORE (COnnecting REpositories)