Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model

The pharmacokinetics and therapeutic efficacy of gentamicin were investigated in an experimental pleural empyema rabbit model. Pleural effusion was induced by the intrapleural administration of turpentine, and empyema was induced by direct inoculation of the effusion with Klebsiella pneumoniae. Pleural empyema compared with effusion was characterized by lower pH, oxygen tension (PaO2), and glucose levels and higher leukocyte count, lactic acid concentration, and PaCO2. After a single administration, gentamicin was first detectable in the pleural fluid at 60 min, whereas peak levels in empyema were observed at 180 min. Gentamicin persisted in the empyema longer than in blood. Animals treated with gentamicin only had 60% bacterial cure on day 7; those treated with gentamicin in an oxygen chamber had 100% cure on day 5 (P = 0.004). Low oxygen tension diminished the antibacterial efficacy of gentamicin in this model. An increase in oxygen tension improved the therapeutic results without alteration of the pharmacokinetics of gentamicin.