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

Antimicrob Agents Chemother. 2015 Apr;59(4):1905-9. doi: 10.1128/AAC.04232-14. Epub 2015 Jan 12.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

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

Substances

  • Anti-Bacterial Agents
  • Ceftazidime