The effect of commonly used non-antibiotic medications on antimicrobial resistance development in Escherichia coli

Hanbiao Chen1, Sylvia A Sapula1, John Turnidge2

  • 1UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA, Australia.

PubMed

Insights

Common medications like ibuprofen and acetaminophen can increase antibiotic resistance in gut bacteria. This study highlights the risk of non-antibiotic drug use in aged care facilities contributing to antimicrobial resistance (AMR).

Area of Science:

  • Microbiology
  • Pharmacology
  • Public Health

Background:

  • Antimicrobial resistance (AMR) is a significant global health threat, primarily driven by antibiotic overuse.
  • Non-antibiotic medications (NAMs) are increasingly recognized as potential contributors to AMR.
  • Residential aged care facilities (RACFs) frequently use both antibiotics and NAMs, necessitating investigation into their combined effects.

Purpose of the Study:

  • To investigate the potential of commonly used NAMs in RACFs to enhance antibiotic-induced mutagenesis.
  • To identify specific NAMs that contribute to the development of high-level antibiotic resistance.

Main Methods:

  • Exposure of Escherichia coli to gut-relevant concentrations of nine common NAMs (ibuprofen, diclofenac, acetaminophen, furosemide, metformin, atorvastatin, tramadol, temazepam, pseudoephedrine).
  • Assessment of mutagenesis and ciprofloxacin resistance.
  • Whole-genome sequencing to identify genetic mutations.
  • Analysis of drug efflux pump gene expression.

Main Results:

  • Ibuprofen and acetaminophen significantly increased mutation frequency and conferred high-level ciprofloxacin resistance in E. coli.
  • Whole-genome sequencing revealed mutations in GyrA, MarR, and AcrR genes.
  • Mutations in MarR and AcrR correlated with the overexpression of the AcrAB-TolC drug efflux pump.
  • Co-exposure to two NAMs further amplified mutation rates and resistance levels.

Conclusions:

  • Certain non-antibiotic medications, notably ibuprofen and acetaminophen, can promote antibiotic resistance.
  • The study identifies specific genetic mechanisms, including efflux pump upregulation, involved in NAM-mediated AMR.
  • Findings underscore the need to evaluate polypharmacy in aged care settings for potential AMR risks.

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