Therapeutic efficacy of continuous versus intermittent administration of ceftazidime in an experimental Klebsiella pneumoniae pneumonia in rats

Abstract

An experimental Klebsiella pneumoniae pneumonia in rats was used to study the influence of continuous or of intermittent (8-hr intervals) administration of ceftazidime on therapeutic efficacy. Antimicrobial response was evaluated with respect to the calculated total daily dose that protected 50% of the animals from death (PD50) until 16 days after termination of a four-day treatment. When antibiotic treatment was started 5 hr after bacterial inoculation, the PD50 values after continuous and after intermittent administration of ceftazidime were 0.36 and 1.42 mg/kg per day, respectively (P less than .001). With a delay in the administration of the antibiotic to 34 hr after inoculation, the respective PD50 values were 1.08 and 13.06 mg of ceftazidime/kg per day (P less than .001). These studies show an improved therapeutic efficacy that increased with a delay in treatment when ceftazidime was administered by continuous infusion as compared with administration at 8-hr intervals. Continuous administration of PD50 doses of ceftazidime resulted in serum levels that were constantly below the MIC of the infecting Klebsiella strain.