Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia

Abstract

Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia. Prospective experimental study Eighteen anesthetized and ventilated piglets Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16 mg/l). Ceftazidime was administered either through a continuous infusion of 90 mg/kg per 24 h after a bolus of 30 mg/kg or by an intermittent infusion of 30 mg/kg per 8 h. Piglets were killed 24 h after the initiation of continuous ceftazidime (n = 6), and 1 h (peak, n = 6) and 8 h (trough, n = 6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7 +/- 3.8 microg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1 +/- 2.4 microg/g and 0.6 +/- 1 microg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.10(3) vs. 4.10(2) cfu/g). Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.