Meropenem, Cefepime, and Piperacillin Protein Binding in Patient Samples

Area of Science:

• Pharmacology
• Infectious Diseases
• Clinical Pharmacy

Background:

• Drug-resistant bacterial infections pose significant mortality risks and treatment challenges.
• Beta-lactam antibiotics, including meropenem, cefepime, and piperacillin, are time-dependent, requiring concentrations above the minimum inhibitory concentration for efficacy.
• Optimizing therapeutic strategies necessitates understanding antibiotic protein binding.

Purpose of the Study:

• To determine the extent and variability of protein binding for meropenem, cefepime, and piperacillin in patient plasma.
• To assess how protein binding influences the free drug concentrations of these critical antibiotics.

Main Methods:

• Plasma samples were collected from 95 patients in a tertiary care hospital.
• Ultrafiltration was used to separate bound and unbound drug fractions.
• Liquid chromatography-tandem mass spectrometry quantified total and free drug concentrations to determine protein binding.

Main Results:

• Median unbound fractions (fu) were 62.5% for meropenem, 61.4% for cefepime, and 48.3% for piperacillin.
• Increased meropenem concentration correlated with increased fu (r = 0.37, P = 0.045).
• Increased albumin concentration correlated with decreased piperacillin fu (r = -0.56, P = 0.005).

Conclusions:

• Observed average unbound fractions were lower than previously reported in literature.
• Significant variability in unbound fractions was identified for all three antibiotics.
• Direct measurement of free drug concentrations is recommended for effective patient management.