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Extracellular concentrations of fosfomycin in lung tissue of septic patients
Veronika Matzi1, Jörg Lindenmann, Christian Porubsky
1Division of Thoracic and Hyperbaric Surgery, Medical University of Graz, Graz, Austria.
Objectives:
The present investigation explored the ability of fosfomycin to penetrate lung tissue of septic patients by utilizing the microdialysis technique.
Methods:
After microdialysis probe insertion into healthy and infected lung tissue, a single intravenous dose of 4 g of fosfomycin was administered.
Results:
The mean C(max), T(max), AUC(0-4) and AUC(0-infinity) for healthy lung were 131.6 +/- 110.6 mg/L, 1.1 +/- 0.4 h, 242.4 +/- 101.6 mgxh/L and 367.6 +/- 111.9 mgxh/L, respectively. The corresponding values for infected lung were 107.5 +/- 60.2 mg/L, 1.4 +/- 0.5 h, 203.5 +/- 118.4 mgxh/L and 315.1 +/- 151.2 mgxh/L. The half-life of fosfomycin ranged from 2.2 to 2.7 h between compartments. The magnitude of lung tissue penetration, as determined by the ratios of the AUC(0-infinity) for lung to the AUC(0-infinity) for plasma, was 0.63 +/- 0.31 and 0.53 +/- 0.31 for healthy and infected lung, respectively.
Conclusions:
We conclude that fosfomycin achieves antimicrobially effective concentrations in infected lung tissue.
Insights
Fosfomycin effectively penetrates infected lung tissue in septic patients, reaching concentrations sufficient for antimicrobial activity. This study used microdialysis to measure drug levels in lung tissue following intravenous administration.
Area of Science:
- Pharmacokinetics
- Infectious Diseases
- Pulmonary Medicine
Background:
- Sepsis can lead to severe lung infections.
- Understanding antibiotic penetration into lung tissue is crucial for effective treatment.
- Fosfomycin is a broad-spectrum antibiotic with potential utility in severe infections.
Purpose of the Study:
- To investigate the penetration of fosfomycin into human lung tissue.
- To determine if fosfomycin achieves therapeutic concentrations in infected lung tissue of septic patients.
Main Methods:
- Microdialysis probes were inserted into healthy and infected lung tissue in septic patients.
- A single intravenous dose of 4 g of fosfomycin was administered.
- Fosfomycin concentrations in lung tissue and plasma were measured over time.
Main Results:
- Fosfomycin achieved mean concentrations of 107.5 mg/L in infected lung tissue.
- The ratio of lung tissue to plasma concentration (AUC) was 0.53 in infected lung.
- Fosfomycin's half-life in lung tissue ranged from 2.2 to 2.7 hours.
Conclusions:
- Fosfomycin penetrates infected lung tissue effectively.
- Achieved concentrations support the use of fosfomycin for treating lung infections in septic patients.
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