High extracellular levels of cefpirome in unaffected and infected lung tissue of patients

Abstract

Objectives: The objective of the present investigation was to measure the extracellular concentrations of cefpirome in unaffected and infected lung tissue of septic patients. Methods: A single intravenous dose of 30 mg/kg total body weight of cefpirome was administered to eight patients every 12 h prior to insertion of microdialysis probes into lung tissue. Results: The median (minimum, maximum) peak concentration (Cmax), time to Cmax (Tmax), area under the concentration-time curve from 0 to 4 h (AUC0-4) and AUC0-∞ of unbound cefpirome for unaffected lung were 48 (32, 107) mg/L, 0.83 (0.17, 3.17) h, 117 (60, 177) mg·h/L and 182 (80, 382) mg·h/L, respectively. The corresponding values for infected lung tissue were 45 (6, 122) mg/L, 1.17 (0.83, 2.83) h, 92 (17, 253) mg·h/L and 206 (49, 379) mg·h/L, respectively. The median apparent terminal elimination half-lives (t1/2z) of cefpirome were 2.61, 3.05 and 3.39 h for plasma, unaffected lung and infected lung, respectively. The median ratios of the AUC0-∞ for lung to the AUC0-∞ for plasma were 0.63 (0.19, 1.55) and 0.46 (0.32, 0.98) for unaffected and infected lung, respectively. Conclusions: We provide strong evidence that cefpirome penetrates effectively into the extracellular space fluid of lung tissue. Under steady-state conditions, the median concentrations of cefpirome in plasma, unaffected lung and infected lung exceeded the MICs of the majority of relevant bacteria over the entire dosing interval of up to 12 h after intravenous administration of a dose of 30 mg/kg total body weight. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.