Steady-state plasma and intrapulmonary concentrations of cefepime administered in continuous infusion in critically ill patients with severe nosocomial pneumonia

Objective. To determine the steady-state plasma and epithelial lining fluid concentrations of cefepime administered in continuous infusion in critically ill patients with severe bacterial pneumonia. Design: Prospective, open-label study. Setting: An intensive care unit and research ward in a university hospital. Patients. Twenty adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation were enrolled. Interventions. All subjects received a 30-min intravenous infusion of cefepime 2 g followed by a continuous infusion of 4 g over 24 hrs. The concentrations of cefepime in plasma and epithelial lining fluid were determined at steady state after 48 hrs of therapy with high performance liquid chromatography. Measurements and Main Results. The mean +/- SD steady-state plasma and epithelial lining fluid concentrations of cefepime 4 g in continuous infusion were 13.5 +/- 3.3 mug/mL and 14.1 +/- 2.8 mug/mL, respectively, with a mean percentage penetration of cefepime into epithelial lining fluid of about 100%. Conclusions: The administration of 4 g of cefepime in continuous infusion in critically ill patients with severe nosocomial pneumonia appears to optimize the pharmacodynamic profile of this beta-lactam by constantly providing concentrations in excess of minimal inhibitory concentration of most of susceptible organisms over the course of therapy in both serum and epithelial lining fluid.