Individual meropenem epithelial lining fluid and plasma PK/PD target attainment

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Infectious Diseases
• Critical Care Medicine

Background:

• Epithelial lining fluid (ELF) drug concentrations are crucial for effective antibiotic treatment, but plasma levels are often used as a surrogate.
• The reliability of plasma meropenem concentrations for predicting target attainment in ELF remains unclear.

Purpose of the Study:

• To compare meropenem target attainment in plasma versus ELF using prospective patient samples.
• To evaluate the impact of patient-specific and population-level factors on meropenem pharmacokinetic/pharmacodynamic (PK/PD) targets.

Main Methods:

• Prospective collection of plasma and ELF samples from patients receiving meropenem.
• Evaluation of 24-hour time above minimum inhibitory concentration (T>MIC) at 1xMIC and 4xMIC targets.
• Analysis of patient-level (fixed MIC) and population-level (cumulative fraction of response - CFR) targets.

Main Results:

• Plasma overestimated ELF target attainment in up to 30% of patients.
• Higher creatinine clearance (>115 mL/min) was associated with reduced ELF target attainment.
• Loading doses significantly increased CFR for Pseudomonas aeruginosa in both plasma and ELF.

Conclusions:

• Plasma meropenem concentrations are not a reliable surrogate for ELF target attainment.
• Patient factors like creatinine clearance and the use of loading doses influence meropenem efficacy.
• Optimized dosing strategies, potentially including loading doses, are necessary to ensure adequate ELF drug exposure.