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

Rene Niehus, Esther van Kleef, Yin Mo, Agata Turlej-Rogacka, Christine Lammens, Yehuda Carmeli, Herman Goossens, Evelina Tacconelli, Biljana Carevic, Liliana Preotescu, Surbhi Malhotra-Kumar, Ben S Cooper

Research output: Contribution to journalA1: Web of Science-articlepeer-review

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.

Original languageEnglish
Article numbere49206
JournaleLIFE
Volume9
ISSN2050-084X
DOIs
Publication statusPublished - 2020

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Anal Canal/microbiology
  • Anti-Bacterial Agents/adverse effects
  • Bacterial Load
  • Bacterial Proteins/genetics
  • Enterobacteriaceae/drug effects
  • Europe
  • Female
  • Gastrointestinal Microbiome/drug effects
  • Humans
  • Male
  • Middle Aged
  • Models, Theoretical
  • Prospective Studies
  • Ribotyping
  • Time Factors
  • Young Adult
  • beta-Lactam Resistance/genetics
  • beta-Lactamases/genetics

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