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.

Genomic and antigenic diversity of colonizing Klebsiella pneumoniae isolates mirrors that of invasive isolates in Blantyre, Malawi

“…Following QC, 203 KpSC genomes (of the 217 sequenced) were included in our analysis, from 142 participants, a median of 1 (1-2) isolates per participant: 154 isolates from 100 participants with sepsis; 34 from 26 antimicrobial unexposed inpatients and 16 from 15 community members. Participant characteristics and a full analysis of within-participant diversity are presented elsewhere [ 21 ], but where participants contributed multiple samples to the analysis, they were usually of different STs: 48 participants contributed more than one sample to the analysis, 109 samples in total. Of these 72/109 were assigned an ST that was not isolated more than once from a given participant.…”

“…There are limitations to our study. Most importantly, our sampling scheme is not unbiased: ESBL-producing colonizing isolates were selected for, because of the focus on ESBL-producers in the colonization study from which these samples arise [ 21 ]. This focus is because of the significant clinical difficulties ESBL-producing bacteria present in our setting.…”

“…The isolates analysed in this study were colonizing isolates selectively cultured from stool and/or rectal swabs collected from adults in Blantyre, Malawi, as part of a study of longitudinal carriage of ESBL-producing Enterobacterales, as previously described [ 21 ]. Briefly, we recruited three groups of adults (≥16 years): (i) 225 adults with sepsis in the emergency department of Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, (ii) 100 antimicrobial-unexposed adults admitted to QECH and (iii) 100 antimicrobial-unexposed community dwelling adults, who lived within 30 km of Blantyre city.…”

“…These were aerobically cultured overnight at 37 °C on ChromAGAR ESBL-selective chromogenic media (ChromAGAR, France) before being speciated with the API system (Biomeriuex, France). Full longitudinal carriage data are presented elsewhere [ 21 ] but 1416 stool samples were collected from the 425 participants; isolates phenotypically identified as ESBL K. pneumoniae were cultured from 233 samples.…”

“…We, therefore, present the results of a genomic analysis of KpSC genomes, which were sequenced for a study of colonisation with ESBL Enterobacterales in Blantyre, Malawi. The results of that study are presented elsewhere [ 21 ], but the analysis here has three aims: (i) to describe the population structure, serotype diversity, AMR and virulence determinants of colonising KpSC isolates in this setting; (ii) to compare colonizing to previously sequenced Malawian invasive isolates, and (iii) to relate these data to observations made in other parts of the world.…”