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

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 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 decrea se for all). The model predicts that
typical antibiotic exposures can have substantial long-term effects on
blaCTX-M carriage duration.