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Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid
B Allegranzi1, A Cazzadori, G Di Perri
1Departments of Infectious Diseases and Respiratory Medicine, University and Hospital of Verona, Verona, Italy. benealle@yahoo.com
Abstract:
The concentrations of meropenem were measured in plasma, bronchoalveolar lavage (BAL) and epithelial lining fluid (ELF) 0.5-8 h after the administration of a single 1 g iv dose of meropenem. Thirty-five patients undergoing bronchoscopy were studied. Mean concentrations in plasma, BAL and ELF, respectively, measured by high performance liquid chromatography, were as follows: 0.5 h: 25. 96, 0.14, 5.04 mg/L; 1 h: 14.98, 0.09, 7.07 mg/L; 2 h: 12.01, 0.06, 3.86 mg/L; 4 h: 2.51, 0.04, 2.20 mg/L; 6 h: 0.57, 0, 0.59 mg/L; 8 h: 0.29, 0, 0 mg/L. Throughout the 2 h following infusion, concentrations in ELF exceeded the MIC90 for all nosocomial and community-acquired respiratory pathogens, including Pseudomonas aeruginosa (3.05 mg/L), Haemophilus influenzae (0.16 mg/L) and penicillin-resistant Streptococcus pneumoniae (0.86 mg/L). These results support the clinical efficacy of meropenem in the treatment of a wide range of pulmonary infections.
Insights
Meropenem concentrations in lung fluids (bronchoalveolar lavage and epithelial lining fluid) exceeded the minimum inhibitory concentration for common respiratory pathogens for two hours after a single intravenous dose. This supports meropenem
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Infectious Diseases
- Pulmonary Medicine
Background:
- Meropenem is a broad-spectrum carbapenem antibiotic used for serious bacterial infections.
- Understanding meropenem penetration into lung tissues is crucial for optimizing treatment of pulmonary infections.
Purpose of the Study:
- To determine meropenem concentrations in plasma, bronchoalveolar lavage (BAL), and epithelial lining fluid (ELF).
- To evaluate if these concentrations are sufficient to inhibit key respiratory pathogens.
Main Methods:
- A single 1g intravenous dose of meropenem was administered to 35 patients undergoing bronchoscopy.
- Plasma, BAL, and ELF samples were collected at intervals from 0.5 to 8 hours post-dose.
- Meropenem concentrations were quantified using high-performance liquid chromatography (HPLC).
Main Results:
- Peak meropenem concentrations were observed within 0.5 hours in plasma and 2 hours in ELF.
- ELF concentrations remained above the MIC90 for relevant pathogens, including Pseudomonas aeruginosa, for up to 2 hours.
- Plasma and BAL fluid concentrations showed a rapid decline, with BAL fluid often below detectable limits.
Conclusions:
- Meropenem achieves therapeutic concentrations in the epithelial lining fluid of the lungs.
- These concentrations are adequate to inhibit a broad range of respiratory pathogens for a clinically relevant period.
- The findings support the use of meropenem for treating various pulmonary infections.