Lung concentration of ceftazidime administered by continuous versus intermittent infusion in ventilator-associated pneumonia.
Fiche publication
Date publication
janvier 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr JOLLY Damien
Tous les auteurs :
Cousson J, Floch T, Guillard T, Vernet V, Raclot P, Wolak-Thierry A, Jolly D
Lien Pubmed
Résumé
Ceftazidime is a beta-lactam compound that exerts a time-dependent bactericidal effect. Numerous arguments are in favour of continuous administration of ceftazidime, both for reasons of clinical efficacy and to preserve bacteriological mutation. We report a prospective, single-centre, parallel-group, randomized, controlled trial comparing two modes of administration of ceftazidime, namely continuous administration (loading dose 20 mg/kg followed by 60 mg/kg/day) versus intermittent administration (20 mg/kg over 30 minutes every 8 hours) in 34 patients with ventilator-associated pneumonia due to Gram negative bacillus. The study was performed over 48 hours with 13 and 18 assessments of serum ceftazidime in the continuous group (group A) and intermittent group (group B) respectively. Bronchoalveolar lavage (BAL) was performed at steady state in both groups at 44 hours to dose ceftazidime levels in the epithelial lining fluid. We chose a predefined threshold of 20 mg/L for serum concentration of Ceftazidime because of ecological conditions in our center. The median percentage of time above 20mg/L (T>20mg) was 100% in group A vs 46% in B. In group A, 14/17 patients had 100% T>20mg, versus only 1/17 patients in B. In the epithelial lining fluid, median concentration of ceftazidime was 12 mg/L in group A vs 6 mg/L in B. A threshold of 8 mg/L in the epithelial lining fluid was achieved twice as often in group A vs B. This study of ceftazidime concentrations in the epithelial lining fluid indicates that continuous infusion presents advantages in terms of pharmacodynamics and predictable efficacy in patients presenting ventilator-associated pneumonia.
Référence
Antimicrob Agents Chemother. 2015 Jan 12. pii: AAC.04232-14.