Plasma and lung concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumonia

Objective. To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumonia. Design. Prospective, open-label study. Setting. An intensive care unit and research ward in a university hospital. Patients. A total of 15 adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation were enrolled. Interventions. All subjects received a 30 min intravenous infusion of 2 g ceftazidime followed by a continuous infusion of 4 g over 24 h. The concentrations of ceftazidime in plasma and ELF were determined at steady-state after 2 days of therapy by high performance liquid chromatography. Measurements and main results. The mean +/-SD steady-state plasma and ELF concentrations of 4 g ceftazidime in continuous infusion were 39.6+/-15.2 mug/mL and 8.2+/-4.8 mug/mL, respectively, showing a mean +/-SD percentage penetration of ceftazidime into ELF of 20.6+/-8.9%. Conclusion. The administration of 4 g ceftazidime in continuous infusion in critically ill patients with severe nosocomial pneumonia provides concentrations in excess of the minimal inhibitory concentration of many susceptible organisms over the course of therapy both in serum and ELF. However, for some pathogens such as P. aeruginosa, higher doses of ceftazidime should be administered, or another agent should be used in combination.