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The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects

Sara Van den Bossche1, Emma De Broe1, Tom Coenye1

  • 1Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.

European Respiratory Review : an Official Journal of the European Respiratory Society
|September 16, 2021
PubMed

Insights

Pseudomonas aeruginosa infections in cystic fibrosis (CF) are hard to treat because standard lab tests don't predict how well antibiotics work in the CF lung. Understanding the CF lung environment is key to better treatment.

Area of Science:

  • Pulmonary Medicine
  • Infectious Diseases
  • Microbiology

Background:

  • Chronic airway colonization by Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients.
  • Despite antibiotic treatment, P. aeruginosa often persists in CF airways, leading to poor clinical outcomes.
  • Current in vitro antibiotic susceptibility assays are unreliable predictors of in vivo efficacy in CF lung infections.

Purpose of the Study:

  • To review factors contributing to the discrepancy between in vitro antibiotic activity and in vivo clinical efficacy in CF.
  • To highlight the influence of the CF lung microenvironment on antibiotic effectiveness.
  • To emphasize the need for improved understanding of CF lung conditions for better treatment strategies.

Main Methods:

  • Review of existing literature on P. aeruginosa in CF lung infections.
  • Analysis of host and microbial factors influencing antibiotic activity within the CF lung.
  • Discussion of the limitations of current in vitro susceptibility testing.

Main Results:

  • The CF lung microenvironment (including iron, mucus, immune mediators, oxygen, and microbiota) significantly impacts antibiotic activity.
  • Antibiotic efficacy in vivo differs from in vitro predictions due to these complex microenvironmental factors.
  • Significant patient-to-patient variability exists in the CF lung microenvironment and microbiota.

Conclusions:

  • A deeper understanding of the CF lung microenvironment and microbial diversity is crucial.
  • Improved in vitro models that mimic the CF lung are needed to enhance susceptibility testing.
  • Optimizing antibiotic selection based on a better understanding of the CF environment can improve treatment success rates.

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