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In vivo dynamics of carbapenem-resistant Pseudomonas aeruginosa selection after suboptimal dosing

Vincent H Tam1, Kimberly R Ledesma, Amy N Schilling

  • 1University of Houston College of Pharmacy, Houston, TX 77030, USA.

Diagnostic Microbiology and Infectious Disease
|July 28, 2009
PubMed

Insights

Suboptimal meropenem dosing in mice with Pseudomonas aeruginosa pneumonia can lead to the selection of resistant bacterial strains. This highlights the importance of appropriate antibiotic dosing to prevent antimicrobial resistance in vivo.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Previous in vitro studies indicated that suboptimal carbapenem exposure can select for Pseudomonas aeruginosa resistance.
  • The in vivo relevance of these findings remains incompletely understood.

Purpose of the Study:

  • To investigate the impact of meropenem exposure on the selection of Pseudomonas aeruginosa resistance in a murine pneumonia model.
  • To evaluate the relationship between antibiotic dosing and the emergence of resistant bacterial populations in vivo.

Main Methods:

  • A neutropenic murine pneumonia model was established using Pseudomonas aeruginosa.
  • Mice received meropenem (400 or 50 mg/kg) or placebo intraperitoneally every 8 hours post-infection.
  • Bacterial burden in lung tissue was quantified, and survival rates were assessed.

Main Results:

  • The higher dose of meropenem (400 mg/kg) significantly improved survival.
  • However, selective amplification of the OprD(-) mutant population was observed in 20% to 30% of treated animals.
  • These findings suggest that incomplete meropenem exposure can drive resistance selection.

Conclusions:

  • Suboptimal meropenem exposure in vivo may facilitate the selection of resistant Pseudomonas aeruginosa strains.
  • Appropriate dosing strategies are crucial for effective treatment and preventing antimicrobial resistance.
  • This study underscores the clinical significance of pharmacokinetic/pharmacodynamic targets in antibiotic therapy.

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