Intérêt pharmacodynamique de la perfusion continue vs l'administration intermittente de ceftazidime dans les pneumonies nosocomiales sévères

Abstract

Goal of the study. – It is well known today that the main determinant of beta-lactam antibiotics efficacy is the duration of the time that concentrations remain in excess of the minimum inhibitory concentration (MIC) of susceptible organism over the course of therapy. This prospective study aimed to evaluate the efficacy, in term of pharmacodynamic profile, of continuous infusion versus intermittent administration of ceftazidime in intensive care unit patients with severe nosocomial pneumonia. Patients and methods. – 16 patients under mechanical ventilation with nosocomial pneumonia were randomised to receive either 60 mg/kg/day ceftazidime by constant rate infusion following a 20 mg/kg loading dose (Group A) or 20 mg/kg every 8 hour by intravenous bolus injection (Group B). In both groups, serial blood samples were collected during 48 hours (12 and 18 samples in Group A and B, respectively) after the start of drug administration. Plasma concentrations of ceftazidime were measured by high performance liquid chromatography. Based on our local bacteriological conditions, the pharmacodynamic profile of ceftazidime was assessed as the duration of time the plasma concentration remained above a desired target concentration of 20 mg/l for each regimen. Results. – The mean time (expressed as a percentage) for which plasma ceftazidime concentrations were above 20 mg/l was 100% for the continous infusion group (Group A) and 56 ± 33% for the intermittent administration group (Group B). Conclusion. – These findings show that ceftazidime administered by continuous infusion in critically ill patients under mechanical ventilation with nosocomial pneumonia appears to substantially improve the pharmacodynamic profile of this beta-lactam compared to the intermittent regimen.