Dynamics of gut mucosal colonisation with extended spectrum beta-lactamase producing Enterobacterales in Malawi

Abstract Shortening courses of antimicrobials has been proposed to reduce risk of antimicrobial resistant (AMR) infections, but acquisition and selection dynamics under antimicrobial pressure at the individual level are poorly understood. We combine multi-state modelling and whole-genome sequencing to understand colonisation dynamics of extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) in Malawian adults. We demonstrate prolonged post-exposure antibiotic effect, meaning short courses exert similar colonisation pressure to longer ones. Genome data does not identify widespread hospital-associated ESBL-E transmission, hence apparent acquisitions may be selected from the patient microbiota by antimicrobial exposure. Understanding ESBL-E dynamics under antimicrobial pressure is crucial for evidence-based stewardship protocols.