Pharmacokinetic/ Pharmacodynamic Study On Ceftazidime Administered In Continuous Versus Intermittent Infusion In A Pseudomonas Aeruginosa Rabbit Pneumonia Model

Objectives: In oder to evaluate the Pharmacokinetic/ pharmacodynamic characteristic, the penetration rates of ceftazidime into lung, the curative effects and drug resistance of ceftazidime administered in continuous versus intermittent infusion in a Pseudomonas aeruginosa rabbit pneumonia model.Methods: 36 rabbits were infected with Pseudomonas aeruginosa to make rabbit pneumonia models. These rabbits were randomly divided into 6 sub-groups(n=6 for each group).Ceftazidime was given either as continuous infusion(CI)or as intermittent infusion per 12 hours(IA) with the same daily dose(50 mg/kg/24 h, 25 mg/kg/24 h, 15mg/kg/24 h respectively). 6 more rabbits were included without drug treatments as control . Venous blood samples and bronchoalveolar lavage fluid( BALF ) samples were collected at different time points to determine the concentrations of ceftazidime by HPLC. Pharmacokinetic analysis was carried out for both regiments,and the parameters including the time above the MIC,4MIC(T>MIC,T>4MIC), the area under the concenrtration–time curve(AUC), inhibitory quotient(IQ)were compared. Ceftazidime concentrations in epithelial lining fluid(ELF)calculated and the penetrations of ceftazidime into lung were compared as well. Curative effect were evaluated by observing the symptoms,physical signs in the course of the treatments,and the lung pathological characters were evaluated at the end of the course(120 hour). MICs 0f Pseudomonas aeruginosa isolated at the end were determined by agar dilution following NCCLS methodology to evaluate the Emergence of multidrug resistance.Result:For the sub-groups with same daily doses, Significantly higher T>MIC,T>4MIC were obtained for the continuous versus intermittent administration. The IQswere higher for intermittent administration. No statistically significant different AUCs and penetration rates were found between the two regiments; No statistically significant differences were found among the six sub-groups in the two regiments for the symptom,physical sign of the rabbits except the IA of 15mg/kg/24 h; The pathologic examination demonstraded that the improvment is better with continuous administration than intermittent infusion, as for the same regiment, the higher the daily dose,the better.The susceptibility test showned that after the administration of caftazidime of 120 hours, no emergence of multidrug resistance were found except the sub-group of IA of 15mg/kg/24 h.Conclusion: continuous administration of ceftazidime is more efficacious compared with intermittent administration against pseudomonas aeruginosa due to its better pharmacokinetic characteristics and less emergence of multidrug resistance.