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Antibiotic Selection Pressure Determination through Sequence-Based Metagenomics.

Matthias Willmann1, Mohamed El-Hadidi2, Daniel H Huson2

  • 1Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany will80@gmx.de.

Antimicrobial Agents and Chemotherapy
|September 16, 2015
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Summary
This summary is machine-generated.

Ciprofloxacin treatment alters gut antibiotic resistance genes (ARGs). While some ARGs increased, others decreased, with recovery varying post-treatment. This highlights the need to consider ARGs when selecting antibiotics.

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Area of Science:

  • Microbiology
  • Genetics
  • Pharmacology

Background:

  • The human gut harbors a dynamic reservoir of antibiotic resistance genes (ARGs).
  • Antimicrobial treatments significantly impact the gut resistome, promoting resistance gene transfer and selection.
  • Understanding these impacts is crucial for managing antibiotic resistance.

Purpose of the Study:

  • To monitor the development of intestinal ARGs during a 6-day ciprofloxacin treatment course in healthy individuals.
  • To quantify the selection pressure exerted by ciprofloxacin on the intestinal resistome.
  • To introduce a novel algorithm for analyzing antibiotic selection pressure in clinical settings.

Main Methods:

  • Sequenced-based metagenomics and ARG quantification methods were employed.
  • Fixed- and random-effect models were used to determine ARG abundance changes per defined daily dose of ciprofloxacin.
  • Analysis focused on shifts in ARG composition and abundance.

Main Results:

  • Ciprofloxacin treatment caused significant shifts in the intestinal resistome composition.
  • Strong positive selection for class D beta-lactamases was observed in one individual, partly on mobile genetic elements.
  • A trend towards negative selection for class A beta-lactamases was noted. ARG composition partially returned to baseline within 4 weeks post-treatment.

Conclusions:

  • Antibiotic treatment profoundly affects the gut resistome, with varying selection pressures on different ARGs.
  • A novel analysis algorithm can quantify antibiotic selection pressure, aiding in the choice of antimicrobial agents with lower selective impact.
  • Minimizing selective pressure from antibiotics can reduce the spread of resistance and hospital-acquired infections.