Lung concentrations of ceftazidime administered by continuous versus intermittent infusion in patients with ventilator-associated pneumonia.

Abstract

Ceftazidime is a beta-lactam compound that exerts a time-dependent bactericidal effect. Numerous arguments are in favor of continuous administration of ceftazidime, both for reasons of clinical efficacy and to preserve bacteriological mutation. We report a prospective, single-center, parallel-group, randomized, controlled trial comparing two modes of administration of ceftazidime, namely, continuous administration (loading dose of 20 mg/kg of body weight followed by 60 mg/kg/day) versus intermittent administration (20 mg/kg over 30 min every 8 h) in 34 patients with ventilator-associated pneumonia due to Gram-negative bacilli. The study was performed over 48 h with 13 and 18 assessments of serum ceftazidime in the continuous-infusion group (group A) and the intermittent-fusion group (group B), respectively. Bronchoalveolar lavage (BAL) was performed at steady state in both groups at 44 h to determine ceftazidime levels in the epithelial lining fluid. We chose a predefined threshold of 20 mg/liter for serum concentrations of ceftazidime because of ecological conditions in our center. The median time above 20 mg/liter (T>20 mg) was 100% in group A versus 46% in group B. In group A, 14/17 patients had 100% T>20 mg, versus only 1/17 patients in group B. In the epithelial lining fluid, the median concentration of ceftazidime was 12 mg/liter in group A versus 6 mg/liter in group B. A threshold of 8 mg/liter in the epithelial lining fluid was achieved twice as often in group A as in group 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.

• Authors: Joël Cousson, Thierry Floch, Thomas Guillard, Véronique Vernet, Pascal Raclot, Aurore Wolak-Thierry, Damien Jolly
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 4 Pg. 1905-9 (Apr 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 25583727 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Ceftazidime

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Area Under Curve
• Bronchoalveolar Lavage Fluid
• Ceftazidime (administration & dosage, pharmacokinetics, therapeutic use)
• Endpoint Determination
• Epithelium (metabolism)
• Female
• Gram-Negative Bacterial Infections (drug therapy, microbiology)
• Humans
• Infusions, Intravenous
• Lung (metabolism)
• Male
• Middle Aged
• Pneumonia, Ventilator-Associated (drug therapy, metabolism)
• Prospective Studies