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.
Elife. 2020 May 7;9:e49206. doi: 10.7554/eLife.49206., 05/2020.
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: ClinicalTrials.gov 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.