Pharmacokinetics and Pharmacodynamics of Continuous and Intermittent Ceftazidime during the Treatment of Nosocomial Pneumonia

Objective: This study aimed too compare the pharmacokinetic and pharmacodynamic profile of intermittent and continuously infused ceftazidime in patients with nosocomial pneumonia. Design and Setting: Prospective, randomised study set in a large community-teaching hospital. Interventions: Thirty-four patients receiving ceftazidime either as an intermittent infusion or a continuous infusion underwent blood sampling for drug concentration determinations between days 2 to 5 of therapy. In addition, at study enrolment sputum samples were obtained for Gram’s stain and culture. The minimum inhibitory concentration (MIC) of isolated organisms to ceftazidime was determined using the broth microdilution technique. Main Outcome Measures: Pharmacokinetic parameters were derived individually for each patient. The pharmacodynamic profile of ceftazidime was assessed as the duration of time the serum concentration remained above the MIC (T > MIC) of the organism(s) for each regimen. Results: Patients were well matched for demographic variables. The pharmacokinetic parameter estimates (mean ± SD) for patients receiving the intermittent infusion therapy were as follows: maximum concentration in serum 106.5 ± 34.6 mg/L; half-life 3.2 ± 2.5 hours; total body clearance (CL t ) 142.5 ± 59 ml/min. The steady-state concentration with the continuous infusion regimen was 17.4 ± 6.1 mg/L, while the CL t was similar at 133.2 ± 37 ml/min. Forty-six pathogens were isolated in 27 patients. The continuous infusion regimen maximised the pharmacodynamics of ceftazidime as T > MIC was 100% of the dosage interval in all patients, whereas the intermittent infusion regimens resulted in T > MIC values of 56 to 100%. Conclusions: In critically ill patients with nosocomial pneumonia the administration of ceftazidime by continuous infusion appears to optimise the pharmacodynamic profile of this β-lactam by constantly providing concentrations in excess of the MIC of susceptible organisms over the course of therapy.