Ceftazidime pulmonary epithelial lining fluid concentrations during continuous and intermittent infusion in swine

The pharmacokinetics and pharmacodynamics (T>MIC) of ceftazidime in the plasma and pulmonary epithelial lining fluid (ELF) were compared following intermittent (IC) and continuous ceftazidime (CC) infusion (60 mg/kg/d) in nine crossbred male intact pigs. The ceftazidime plasma half-life, volume of distribution, clearance, and area under the plasma concentration-time curve were similar between the IC and CC regimens. Ceftazidime area under the ELF concentration-time curve were 29.6% and 23.4% of the area under the plasma concentration-time curve for the IC and CC regimens, respectively. The ceftazidime half-life in the ELF was approximately two-fold longer compared to the plasma half-life. This suggests that the penetration of ceftazidime into the ELF is membrane-limited and may not display compartmental pharmacokinetic characteristics. Using T>MIC as a surrogate marker of efficacy, ceftazidime's limited ELF penetration may hinder pharmacodynamic optimization against less susceptible gram-negative bacteria causing pneumonia.