Pharmacodynamic considerations in the treatment of moderate to severe pseudomonal infections with cefepime

Pseudomonas aeruginosa is one of the more common and clinically difficult-to-treat causes of hospital-acquired infections. Cefepime is a broad-spectrum cephalosporin with potent in vitro activity against Gram-positive cocci, enteric Gram-negative bacilli and Pseudomonas aeruginosa. Cephalosporins exhibit time-dependent bactericidal activity and lack prolonged post-antibiotic effects against Enterobacteriaceae and P. aeruginosa. In non-clinical models of infection against Enterobacteriaceae and P. aeruginosa, antibacterial effects are observed when serum levels are above the MIC for as little as 35% of the dosing interval and are maximized when levels exceed the MIC for 60-70% of the dosing interval. Based on the MIC distribution for P. aeruginosa and pharmacokinetic data obtained from patients with serious bacterial infections (including pneumonia and sepsis), time above MIC targets can be met in infected patients following 2 g doses of cefepime administered every 12 h. An understanding of the integration of target patient population pharmacokinetics and the MIC distribution is crucial for selecting effective dosage regimens, especially in the setting of empirical therapy. Moreover, sufficient clinical outcome data in infected patients exist and support these pharmacodynamic conclusions.