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The effect of combining antibiotics on resistance: A systematic review and meta-analysis

Berit Siedentop1,2, Viacheslav N Kachalov2,3, Christopher Witzany1

  • 1Institute of Integrative Biology, Department of Environmental Systems Science, ETH Zürich, Zurich, Switzerland.

Elife
|December 20, 2024
PubMed
Abstract

Insights

Antibiotic combination therapy

Area of Science:

  • Medical Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Understanding antibiotic resistance evolution is crucial.
  • The impact of combination therapy on resistance is not fully understood.
  • This study investigates how combining antibiotics affects resistance development within patients.

Purpose of the Study:

  • To analyze the effect of antibiotic combination therapy on the development of bacterial resistance.
  • To explore conditions under which combination therapy might decelerate resistance.
  • To assess resistance development across diverse bacterial pathogens and antibiotic regimens.

Main Methods:

  • Systematic review and meta-analysis of (quasi)-randomised controlled trials (RCTs).
  • Searched CENTRAL, EMBASE, and PubMed databases up to November 24, 2022.
  • Included trials comparing different numbers of antibiotics; assessed resistance acquisition from baseline to follow-up cultures.

Main Results:

  • 42 trials were identified, with 29 (5054 patients) included in the analysis.
  • The pooled odds ratio for resistance acquisition with more antibiotics was 1.23 (95% CI 0.68-2.25), indicating substantial heterogeneity (I²=77%).
  • Tentative evidence suggests potential benefits or harms of combination therapy depending on the pathogen or condition.

Conclusions:

  • Evidence from RCTs on combination therapy's impact on resistance is limited and inconclusive.
  • Current data is compatible with both beneficial and detrimental effects.
  • Further powered trials and well-designed observational studies are needed to clarify combination therapy's role in resistance development.
Keywords:
antibiotic resistancecombination therapyhumaninfectious diseasemedicinemeta-analysismicrobiologyresistance evolutionsystematic review

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