Lung Concentrations of Ceftazidime in Patients With Ventilator-associated Pneumonia (CEFTALC)

Comparison of Lung Concentrations of Ceftazidime Administered by Continuous Versus Intermittent Infusion in Patients With Ventilator-associated Pneumonia

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. The investigators 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. The investigators chose a predefined threshold of 20 mg/liter for serum concentrations of ceftazidime because of ecological conditions in our center.

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Drug: ceftazidime; Drug: ceftazidime

Detailed Description

Primary objective

The main objective of this study is to show the continuous administration of superiority ceftazidime versus intermittent administration, in terms of lung tissue concentration of ceftazidime in mechanically ventilated patients with pneumonia caused by a bacillus gram negative.

Methods

Trial

Prospective therapeutic trial in parallel groups, controlled, randomized, single center comparing two methods of administration of ceftazidime (continuous administration by self-pulsed syringe versus discontinuous administration regimens to 3 injections per 24 hours) in patients with severe pneumonia in mechanically ventilated due to gram negative bacillus.

Population

Patients will be enrolled in the Intensive Care Unit of the Reims university hospital.

All patients meeting the inclusion criteria and respecting the criteria of non-inclusions (see below) will be consecutively enrolled in the study after obtaining consent. The allocation of one of the 2 treatment modality will be made by randomization.

Variables and parameters collected in the study:

In addition to sociodemographic variables, variables for inclusion in the study and judgment criteria, different blood and urine tests will be collected:

1. Criteria for inclusion and non-inclusion (see above);

2. Outcome:

   i) concentration in the cell film ceftazidime;

   ii) serum concentration of ceftazidime;

   iii) period during which the serum concentration of ceftazidime is higher than 20 mg/l;

3. Socio-demographic variables: Age, Gender;
4. Blood Assays: Blood gas; Blood Urea, créatinimémie and chemistry panel; serum protein; Complete Blood Count; Beta HCG if women of childbearing age; Liver function tests: AST, ALT, GGT, bilirubin, alkaline phosphatase;
5. Urinary Assays: Creatinine clearance and urinary electrolytes.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Reims
    • France, Reims, France, 51092
      • CHU Reims

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age >18 years;
• Patients hospitalized in the general intensive care unit of the University Hospital of Reims;
• Nosocomial pneumonia with Gram-negative.

Exclusion Criteria:

• Weight >110 kg;
• Pregnant or breastfeeding women;
• Known allergy to beta - lactam antibiotics;
• Renal impairment: clearance <60 calculated by the Cockcroft and Gault;
• Known history of pulmonary fibrosis;
• Patients included in another research protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: continuous administration of ceftazidime	Drug: ceftazidime; 20 mg/kg of body weight followed by 60 mg/kg/day; Drug: ceftazidime; 20 mg/kg over 30 min every 8 h
Experimental: intermittent administration of ceftazidime	Drug: ceftazidime; 20 mg/kg of body weight followed by 60 mg/kg/day; Drug: ceftazidime; 20 mg/kg over 30 min every 8 h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
lung tissue concentration of ceftazidime	up to 44 hours

Collaborators and Investigators

• Sponsor: CHU de Reims

Publications and helpful links

General Publications

• Cousson J, Floch T, Guillard T, Vernet V, Raclot P, Wolak-Thierry A, Jolly D. 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (Estimate): July 20, 2016

Study Record Updates

• Last Update Posted (Estimate): July 20, 2016
• Last Update Submitted That Met QC Criteria: July 15, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Anti-Infective Agents; Anti-Bacterial Agents; Ceftazidime
• Other Study ID Numbers: 104R04