| Abstract |
The degree of penetration of newer quinolones and macrolides into the pleural fluid has not been studied. Objective: To determine the degree to which moxifloxacin, levofloxacin and clarithromycin penetrate into empyemic pleural fluid using a new rabbit model of empyema. Methods: An empyema was created via the intrapleural injection of 1mL turpentine followed 24 h later by instillation of 5 mL (1010) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin 30 mg/kg, moxifloxacin and levofloxacin 25 mg/kg each, were administered IV. Antibiotic levels were determined on samples of pleural fluid and bloods collected serially over 12 h. Antibiotic levels were measured using HPLC. Results: Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for clarithromycin (AUCPF / AUCblood ratio of 1.56) followed by moxifloxacin (AUCPF / AUCblood ratio of 1.37) and levofloxacin (ratio of 1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h) and clarithromycin (7.7 h). With clarithromycin, the peak pleural fluid level (CmaxPF of 2.88 μg/mL) occurred 1 h (TmaxPF of 1 h) after infusion and decreased thereafter. The Cmaxblood was 3.53 μg/mL at 1 h after administration. With moxifloxacin, the peak pleural fluid level (CmaxPF of 2.77 μg/mL) occurred 6 h (TmaxPF of 6 h) after infusion and decreased thereafter. The Cmaxblood was 4.81 μg/mL at 1 h after administration. With levofloxacin, the peak pleural fluid level (CmaxPF of 1.39 μg/mL) occurred at 6 h (TmaxPF of 6 h) after infusion. The Cmaxblood was 1.88 μg/mL at 1 h after administration. The AUIC in the pleural fluid was 45.99 μg*h/mL for moxifloxacin and 109.45 μg*h/mL for levofloxacin. Conclusion: The levels of quinolones and clarithromycin in the pleural fluid after intravenous administration are inhibitory for most usual pathogens in empyema. The degree of penetration of the antibiotics should be considered when antibiotics are selected for the treatment of patients with empyema.
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Φαρμακοκινητική και φαρμακοδυναμική νεότερων μακρολιδών και κινολονών στη θεραπεία του εμπυήματος σε κονίκλους
