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

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.