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Updated: May 10, 2026

Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
15:43

Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice

Published on: March 17, 2014

Phenotypic convergence and collateral susceptibility development in Pseudomonas aeruginosa under antibiotic exposure

Thomas E van der Schalk1, Matilda Berkell1,2, An Hottebeekx1,2

  • 1Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium.

Npj Antimicrobials and Resistance
|May 8, 2026
PubMed

Insights

Antibiotic resistance in intensive care units (ICUs) can be managed by diversifying antibiotic treatments. This approach leverages collateral effects, where resistance to one drug can increase susceptibility to another, reducing multidrug resistance (MDR) in pathogens like Pseudomonas aeruginosa.

Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Clinical Medicine

Background:

  • Antibiotic combination therapy is standard in ICUs to combat broad-spectrum pathogens.
  • Collateral effects, where resistance to one antibiotic can increase susceptibility to another, are known but often overlooked in clinical practice.
  • Pseudomonas aeruginosa (PA) is a multidrug-resistant (MDR), nosocomial pathogen frequently encountered in ICUs.

Purpose of the Study:

  • To investigate the impact of antibiotic exposure on resistance and collateral effects in Pseudomonas aeruginosa (PA) within an intensive care unit (ICU) setting.
  • To compare in vivo patient data with in vitro adaptive evolution experiments under antibiotic pressure.
  • To evaluate whether empirical antibiotic mixing in ICUs influences the evolution of MDR phenotypes.

Main Methods:

  • Longitudinal analysis of PA isolates from 25 ventilated ICU patients receiving various antibiotics.
  • In vitro adaptive evolution experiments using laboratory PA strains under four different antipseudomonal monotherapies.
  • Correlation analysis between antibiotic administration, resistance changes, and collateral susceptibility patterns.

Main Results:

  • Prolonged antibiotic exposure in vitro and in vivo led to resistance with collateral effects.
  • The number of antibiotics administered did not correlate with resistance to those specific drugs in patients.
  • An inverse correlation was observed between resistance to non-administered antibiotics and the diversity of antibiotic classes used, supporting collateral susceptibility principles.

Conclusions:

  • Empirical antibiotic mixing in ICUs can exploit evolutionary trade-offs to manage antibiotic resistance.
  • Diversifying antibiotic pressure through multi-class exposure may reduce the prevalence and persistence of MDR phenotypes in critical care settings.
  • Real-world evidence supports the strategic use of antibiotic combinations to attenuate MDR evolution in ICUs.

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