title: 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.affiliation: Reims University Hospital, Robert Debré Hospital, Intensive Care Unit, Reims, France University of Reims Champagne-Ardenne, Faculty of Medicine, EA 4687, Reims, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Cousson
authors.affiliation: Reims University Hospital, Robert Debré Hospital, Intensive Care Unit, Reims, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Floch
authors.affiliation: Reims University Hospital, Maison Blanche Hospital, Bacteriological Laboratory, Reims, France University of Reims Champagne-Ardenne, Faculty of Medicine, EA 4687, Reims, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guillard
authors.affiliation: Reims University Hospital, Maison Blanche Hospital, Bacteriological Laboratory, Reims, France University of Reims Champagne-Ardenne, Faculty of Medicine, EA 4687, Reims, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Vernet
authors.affiliation: Reims University Hospital, Robert Debré Hospital, Intensive Care Unit, Reims, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Raclot
authors.affiliation: Reims University Hospital, Robert Debré Hospital, Clinical Research Department, Reims, France University of Reims Champagne-Ardenne, Faculty of Medicine, EA 3797, Reims, France awolak-thierry@chu-reims.fr.
authors.forename: Aurore
authors.initials: A
authors.lastname: Wolak-Thierry
authors.affiliation: Reims University Hospital, Robert Debré Hospital, Clinical Research Department, Reims, France University of Reims Champagne-Ardenne, Faculty of Medicine, EA 3797, Reims, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Jolly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D001992:Bronchoalveolar Lavage Fluid; D002442:Ceftazidime / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023381:Endpoint Determination; D004848:Epithelium / Q000378:metabolism; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007262:Infusions, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime