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

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) in Blantyre, Malawi, over six months and used multi-state modelling and whole-genome sequencing to understand colonisation dynamics of ESBL-E. Models suggest a prolonged effect of antimicrobials such that truncating an antimicrobial course at two days has a limited effect in reducing colonisation. Genomic analysis shows largely indistinguishable diversity of healthcare-associated and community-acquired isolates, hence some apparent acquisition of ESBL-E during hospitalisation 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 colonisation.