Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Colonization dynamics of extended-spectrum beta-lactamase-producing Enterobacterales in the gut of Malawian adults
AU - Lewis, Joseph M
AU - Mphasa, Madalitso
AU - Banda, Rachel
AU - Beale, Mathew A
AU - Heinz, Eva
AU - Mallewa, Jane
AU - Jewell, Christopher
AU - Faragher, Brian
AU - Thomson, Nicholas R
AU - Feasey, Nicholas A
PY - 2022/10/31
Y1 - 2022/10/31
N2 - 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.
AB - 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.
KW - Adult
KW - Anti-Bacterial Agents/pharmacology
KW - Bacteria
KW - Feces/microbiology
KW - Gammaproteobacteria
KW - Humans
KW - Intestines
KW - beta-Lactamases/genetics
U2 - 10.1038/s41564-022-01216-7
DO - 10.1038/s41564-022-01216-7
M3 - Journal article
C2 - 36065064
VL - 7
SP - 1593
EP - 1604
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
IS - 10
ER -