Penetration of meropenem into pneumonic human lung tissue as measured by in vivo microdialysis
Florian Tomaselli1, Alfred Maier, Veronika Matzi
1Department of General, Thoracic and Vascular Surgery, KH der Elisabethinen, Fadingerstr. 1, 4010 Linz, Austria. florian.tomaselli@elisabethinen.or.at
Abstract:
Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values. Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem. The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 +/- 10.9 mg/liter, and that in serum was 47.3 +/- 21.0 mg/liter. The areas under the curve for infected lung tissue (36.2 +/- 17.9 mg. h/liter) and serum (95.4 +/- 46.6 mg. h/liter) revealed a significant difference. This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia. The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.
Insights
Meropenem effectively penetrates infected human lung tissue, reaching therapeutic concentrations in the extracellular fluid. This study demonstrates its excellent distribution for treating lung infections caused by extracellular bacteria.
Area of Science:
- Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Limited data exists on antibiotic pharmacokinetics within infected human lung tissue.
- Understanding drug distribution in lung parenchyma is crucial for effective infection treatment.
Purpose of the Study:
- To measure meropenem penetration into the extracellular fluid of human pneumonic lung tissue.
- To evaluate a microdialysis technique for assessing antibiotic tissue pharmacokinetics.
Main Methods:
- A microdialysis approach was used in seven patients with pneumonia and empyema.
- Meropenem concentrations in lung tissue and serum were measured over 8 hours post-dose.
- Probes were inserted into infected lung and healthy skeletal muscle for comparison.
Main Results:
- The maximum free interstitial concentration of meropenem in infected lung was 11.4 mg/L.
- Area under the curve values showed significant differences between lung tissue and serum.
- The technique allowed for quasi-continuous measurement of free meropenem in lung tissue.
Conclusions:
- Meropenem exhibits excellent distribution into the interstitial space of human pneumonic lung tissue.
- The findings support the use of meropenem for treating lung infections caused by extracellular bacteria.
- Microdialysis is a viable method for real-time pharmacokinetic assessment in infected lung tissue.
