Pleural fluid penetration of moxifloxacin and doripenem: An experimental model of empyema

Abstract

OBJECTIVE: This study aimed to evaluate the penetration of moxifloxacin and doripenem into the pleural fluid (PF) using arabbit model of empyema.METHODS: An empyema was induced using the intrapleural injection of turpentine (1 mL), followed 24 h later by instillationof 5 mL Klebsiella Pneumoniae (ATCC 33495), Fusobacterium nucleatum (ATCC 25586) and Streptokok Pneumoniae (ATCC6305) into the pleural space. After an empyema was corroborated, Moxifloxacin (25 mg/$kg^{-1}$) and Doripenem (20 mg/ $kg^{-1}$)were administered intraperitoneally. To determine the levels of antibiotics measured by High-Performance Liquid Chromatography in pleural and blood samples were obtained serially at 8, 24, 48 and $72^{nd}$ hour.RESULTS: The penetration of both antibiotics into the PF was very good. The penetration rate of doripenem (area underthe curve (AUC) for PF/blood (AUCPF/AUCblood) ratio=1.68) was better than moxifloxacin (ratio=0.78). Equalization timebetween the PF and blood concentration of doripenem was more quickly than moxifloxacin. Peak PF concentration of moxifloxacin was 0,81 μg/$mL^{-1}$ and occurred 8 h after infusion and then gradually decreased; at the beginning of the blood andpleural fluid concentrations of doripenem were equal. While the pleura concentration was increasing, blood concentration wasalmost the same. Doripenem reached a peak concentration (0.54 μg/ml) 24 h post-administration.CONCLUSION: Differences were found in the penetration of the two antibiotics. Doripenem had convenient penetration PFcompared to moxifloxacin. Due to the differences between human and rabbit pleural thickness, doripenem’s pleural penetration should be examined in infection models in animals with equal pleura thickness and clinical trials.