Therapeutic drug monitoring of beta-lactam antibiotics in critically ill adult patients. A single-center prospective observational pilot study

Introduction: Beta-lactams are among the most commonly used antibiotics. Their efficacy is time-dependent, thus the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommends that their plasma concentrations should remain above the minimal inhibitory concentration (MIC) of the pathogenic bacteria through-out the dosing period (100%fT>MIC). However, according to several studies, it appears that the plasma concentrations of beta-lactam antibiotics can be suboptimal in critically ill patients.Objective: The aim of our study was to determine the pharmacodynamic target achievement of beta-lactam antibiotics (meropenem, piperacillin/tazobactam, and ceftriaxone) among critically ill adult patients admitted to an intensive care unit.Method: We conducted a prospective, observational singlecentre study in a teaching hospital. Critically ill patients who were prescribed meropenem, piperacillin or ceftriaxone were enrolled. Trough antibiotic plasma concentration was measured using high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess the achievement of the pharmacodynamic target of 100%fT>MIC. The target concentration was determined based on the definitions of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), depending on the pathogen. The primary endpoint was the proportion of patients not achieving therapeutic plasma concentrations.Results: A total of 60 antibiotic level measurements were performed in 28 patients. The median age of the patients was 64.5 +/- 28,7 years, 80% (n = 22 patients) were male. The reason for admission was medical in 35.7% (n = 10), surgical/trauma in 53.5% (n = 15) and burns in 10.7% (n = 3) of patients. The therapeutic target was not achieved in 39.3% (n = 11) of patients, 66.6% (n = 6) in the meropenem group, 41.6% (n = 5) in the piperacillin group and 12.5% (n = 1) in the ceftriaxone group.Discussion: A significant proportion of critically ill patients receiving beta-lactam antibiotics did not achieve their target concentration, particularly piperacillin and meropenem.Conclusion: Our pilot study confirms the importance of therapeutic drug monitoring in critically ill patients receiving beta-lactam therapy.