Objectives: Pneumonia is one of the most common infections in intensive care patients, and it is often treated with beta-lactam antibiotics. Even if therapeutic drug monitoring in blood is available, it is unclear whether sufficient concentrations are reached at the target site: the lung. The following study was initiated to fill this knowledge gap. Methods: Various compartments from ten patients` explanted lungs were subjected to laboratory analysis. Meropenem was quantified in serum, bronchoalveolar lavage (BAL), microdialysate and homogenized lung tissue with isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS). BAL represents diluted epithelial lining fluid (ELF), and microdialysate represents interstitial fluid (IF). Differences between target site and blood concentrations were investigated. Results: The median meropenem concentration in blood, ELF, IF and tissue were 26.8, 18.0, 12.1 and 9.1 mg/L, respectively. A total of 37.5% of the target site ELF and IF meropenem concentrations were below the clinical EUCAST breakpoint of 8 mg/L. The median ELF/serum quotient was 61.8% (IQR: 24.8%, 87.6%), the median IF/serum quotient was 35.4% (IQR: 23.8%, 54.3%), and the median tissue/serum quotient was 34.2% (IQR: 28.3%, 38.2%). We observed a substantial interindividual variability between the blood and the compartments (ELF, IF), whereas the intraindividual variability was relatively low. Conclusions: Target site measurement in different lung compartments was feasible and successfully applied in a clinical setting. A relevant amount of 37.5% of the target site concentrations fell under the clinical EUCAST breakpoint, indicating subtherapeutic dosing in high-risk patients receiving perioperative antibiotic prophylaxis in lung transplantation.
- Paal, M.
- Scharf, C.
- Denninger, A. K.
- Ilia, L.
- Kloft, C.
- Kneidinger, N.
- Liebchen, U.
- Michel, S.
- Schneider, C.
- Schröpf, S.
- Schuster, C.
- Vogeser, M.
- Weinelt, F.
- Zander, J.
- Zoller, M.
- Schroeder, I.
