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Common non-antibiotic drugs enhance selection for antimicrobial resistance in mixture with ciprofloxacin

April Hayes1, Lihong Zhang1, Jason Snape2

  • 1European Centre for Environment and Human Health, University of Exeter, Penryn, TR109FE, United Kingdom.

ISME Communications
|October 17, 2025
PubMed

Insights

Non-antibiotic drugs (NADs) combined with ciprofloxacin, an antibiotic, more effectively select for antimicrobial resistance (AMR) and alter microbial communities than ciprofloxacin alone. This highlights the importance of studying drug mixtures in AMR development.

Area of Science:

  • Environmental microbiology
  • Molecular biology
  • Public health

Background:

  • Antimicrobial resistance (AMR) is a significant global health threat.
  • Pharmaceuticals exist in the environment and human body as mixtures, not single compounds.
  • Non-antibiotic drugs (NADs) can influence AMR selection, but are often studied in isolation.

Purpose of the Study:

  • To investigate the impact of NADs combined with ciprofloxacin on AMR selection.
  • To analyze changes in the resistome and microbial community composition when exposed to drug mixtures.
  • To determine if drug combinations exhibit stronger AMR selection than single antibiotics.

Main Methods:

  • Growth assays and quantitative PCR (qPCR) to identify selective concentrations.
  • Metagenome sequencing to assess resistome and community composition.
  • Experimental exposure of microbial communities to ciprofloxacin alone and in combination with NADs.

Main Results:

  • Mixtures of NADs and ciprofloxacin altered the selection dynamics of the integrase 1 gene (intI1).
  • Specific AMR genes, such as qnrB, showed stronger selection in the presence of drug mixtures.
  • Exposed microbial communities exhibited distinct changes in composition compared to controls.

Conclusions:

  • NADs in combination with ciprofloxacin demonstrate enhanced selection for AMR compared to ciprofloxacin alone.
  • Drug mixtures induce unique alterations in microbial community structure.
  • Future research on AMR must account for the combined effects of antibiotics and NADs.
Keywords:
antimicrobial resistancemicrobial ecologymixturesnon-antibiotic drugspharmaceuticals

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