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Penetration of meropenem into epithelial lining fluid of patients with ventilator-associated pneumonia

T P Lodise1, F Sorgel, D Melnick

  • 1Ordway Research Institute, Albany, NY 12208, USA.

Antimicrobial Agents and Chemotherapy
|February 9, 2011
PubMed

Insights

Meropenem lung penetration in ventilator-associated pneumonia (VAP) varies widely. Even high doses may not achieve therapeutic targets in many VAP patients due to unpredictable antibiotic concentrations in epithelial lining fluid (ELF).

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Effective antibiotic treatment for ventilator-associated pneumonia (VAP) relies on adequate drug penetration to the infection site.
  • Quantifying lung penetration of antibiotics, specifically β-lactam agents, in VAP patients is crucial but understudied.
  • Previous studies often involved non-infected patients, limiting direct applicability to VAP pharmacodynamics.

Purpose of the Study:

  • To investigate the penetration and pharmacodynamics of meropenem in the epithelial lining fluid (ELF) of patients diagnosed with VAP.
  • To model meropenem concentration-time profiles in both plasma and ELF to understand drug distribution.
  • To estimate the variability in meropenem lung penetration using Monte Carlo simulations.

Main Methods:

  • Collected meropenem plasma and ELF concentration-time data from a multicenter clinical trial involving VAP patients.
  • Utilized a three-compartment model with zero-order infusion and first-order elimination/transfer (BigNPAG) for simultaneous pharmacokinetic modeling.
  • Performed Monte Carlo simulations to predict the range of epithelial lining fluid (ELF) to plasma area under the concentration-time curve (AUC) ratios (AUC(ELF)/AUC(plasma)).

Main Results:

  • The study revealed a broad range of meropenem lung penetration, with the 10th percentile at 3.7% and the 90th percentile at 178% for the AUC(ELF)/AUC(plasma) ratio.
  • Significant variability in meropenem penetration into the ELF was observed among VAP patients.
  • These findings suggest that achieving therapeutic targets for certain pathogens may be challenging for a considerable portion of the VAP population.

Conclusions:

  • Meropenem penetration into the lung in VAP patients exhibits substantial inter-patient variability.
  • Standard dosing or prolonged infusions of meropenem may not consistently ensure adequate drug exposure in the ELF for effective bacterial killing or resistance suppression.
  • Further research is needed to optimize meropenem dosing strategies in VAP to improve clinical outcomes.

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