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Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance

Niehus R, van Kleef E, Mo Y, Turlej-Rogacka A, Lammens C, Carmeli Y,  Goossens H, Tacconelli E, Carevic B, Preotescu L, Malhotra-Kumar S,  Cooper BS

Abstract: Antibiotic-induced perturbation of the human gut flora  is expected to play an important role in mediating the relationship  between antibiotic use and the population prevalence of antibiotic  resistance in bacteria, but little is known about how antibiotics affect  within-host resistance dynamics. Here we develop a data-driven model of  the within-host dynamics of extended-spectrum beta-lactamase (ESBL)  producing Enterobacteriaceae. We use blaCTX-M (the most  widespread ESBL gene family) and 16S rRNA (a proxy for bacterial load)  abundance data from 833 rectal swabs from 133 ESBL-positive patients  followed up in a prospective cohort study in three European hospitals.  We find that cefuroxime and ceftriaxone are associated with increased  blaCTX-M abundance during treatment (21% and 10% daily increase,  respectively), while treatment with meropenem, piperacillin-tazobactam,  and oral ciprofloxacin is associated with decreased blaCTX-M (8% daily  decrease for all). The model predicts that typical antibiotic exposures  can have substantial long-term effects on blaCTX-M carriage duration.

Trial registration: NCT01208519.

Keywords: antibiotic resistance; epidemiology; extended-spectrum beta-lactamase; global health; gut microbiota; human; infectious disease; microbiology; resistance carriage; state-space model; within-host dynamics.

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