Empiric Antibiotic Therapy for Ventilator-acquired Pneumonia With Gram-negative Bacilli in Intensive Care (TARGET-REA)

Empiric Antibiotic Therapy for Ventilator-acquired Pneumonia With Gram-negative Bacilli in Intensive Care: Pharmacodynamic Evaluation and Impact.

this study aims to verify the adequacy of doses of antibiotics prescribed in clinical practice for the treatment of ventilated acquired pneumonia (VAP) in the intensive care unit (ICU) with the pharmacodynamic efficacy criteria considered relevant literature. The impact of these pharmacodynamic parameters on the clinical and microbiological VAP will be evaluated.

Study Overview

• Status: Unknown
• Conditions: Ventilator-associated Pneumonia

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Olivier Pajot, MD; Phone Number: +33 1 34 23 24 51; Email: olivier.pajot@ch-argenteuil.fr

Study Locations

• France
  • Val d'Oise
    • Argenteuil, Val d'Oise, France, 95100
      • Recruiting
      • CH Victor Dupouy
      • Contact: Olivier Pajot, MD; Phone Number: +33 1 34 23 24 15; Email: olivier.pajot@ch-argenteuil.fr
      • Principal Investigator: Olivier Pajot, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Pneumonia acquired in mechanically ventilated patients (PAVM)

Description

Inclusion Criteria:

1. Use of mechanical ventilation for more than 48 hours

2. Clinical suspicion of ventilation-acquired pneumonia (VAP) defined by new radiological persisting infiltrate (or ARDS) AND one of the following features:

   purulent tracheal aspirates OR temperature ≥ 38.3°C OR leukocytosis> 10 giga/L

3. High risk of multidrug-resistant bacteria, defined as either at least 6 days of mechanical ventilation OR antibiotic treatment in the previous 15 days
4. Implementation of a prior distal respiratory sample for microbiological diagnosis by bronchoalveolar lavage (BAL) OR distal sampling by protected catheter (PDP)
5. Age ≥ 18 years
6. Implementing a medical examination
7. Obtain the written consent of the patient, one of its relatives or trusted person previously designated or emergency clause.

Exclusion Criteria:

1. Pregnant woman
2. Expected death within 72 hours of diagnosis of VAP patient
3. Dialysis
4. No affiliation to a social security scheme (beneficiary or legal)
5. Contraindication to one of classes of molecules used antibiotics (β-lactam / Fluoroquinolones / Aminoglycosides), contained in the Summary of Product Characteristics for authorization on the market.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adequate antibiotics	proportion of patients for whom the pharmacodynamic target defined a priori according to data from the literature is reached for each antibiotic anti Gram-negative bacillus used empirically activity (including β-lactams, fluoroquinolones and aminoglycosides)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death		28 days
Bacterial species	Bacterial species in question, defined as any bacteria isolated in significant amounts on the diagnostic breath sampling	28 days
Distribution of the main pharmacodynamic parameters	ratio of the peak serum level (Cmax) on the minimal inhibitory concentration (MIC), ie Cmax/MIC ratio (for aminoglycosides and fluoroquinolones): distribution in the population and proportion of patients with Cmax/MIC> 10; ratio of the Area Under the serum concentration time Curve (AUC) on the MIC, ie AUC/MIC ratio (for fluoroquinolones) : distribution in the population and proportion of patients with an AUC/MIC ratio> 125; percentage of time spent above the MIC between 2 injections, and trough/MIC ratio (for β-lactams): distribution in the population and proportion of patients with a T>MIC of 100% (intermittent infusion) or trough/MIC> 4 (continuous infusion)	28 days
Eradication of gram negative bacilli responsible for VAP	defined as a bacterial count from distal respiratory sample realized during the third day of treatment, less than the threshold for each isolated Gram negative bacilli initially beyond these thresholds	28 days
Number of days alive without mechanical ventilation		28 days
Clinical recovery	defined as patient alive with Clinical Pulmonary Infection Score (CPIS) <8	28 days
Score of organ failure (SOFA)	repeated measures every 48h for 8 days	8 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: April 29, 2014
• First Posted (Estimate): April 30, 2014

Study Record Updates

• Last Update Posted (Estimate): April 18, 2016
• Last Update Submitted That Met QC Criteria: April 15, 2016
• Last Verified: April 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
• Other Study ID Numbers: P1101137