Empiric Antibiotic Therapy for Ventilator-acquired Pneumonia With Gram-negative Bacilli in Intensive Care

• Conditions: Ventilator-associated Pneumonia

• Registration Number: NCT02127528
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-07
• Study First Submitted QC: 2014-04-29
• Study First Posted: 2014-04-30
• Study Start: 2014-05
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-15
• Last Update Posted: 2016-04-18
• Primary Completion: 2016-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
adequate antibiotics	28 days	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)

Secondary Outcome Measures

Name	Time	Method
Bacterial species	28 days	Bacterial species in question, defined as any bacteria isolated in significant amounts on the diagnostic breath sampling
Number of days alive without mechanical ventilation	28 days
Clinical recovery	28 days	defined as patient alive with Clinical Pulmonary Infection Score (CPIS) \<8
Death	28 days
Score of organ failure (SOFA)	8 days	repeated measures every 48h for 8 days
Distribution of the main pharmacodynamic parameters	28 days	1. 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; 2. 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; 3. 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)
Eradication of gram negative bacilli responsible for VAP	28 days	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

Trial Locations

Locations (1)

CH Victor Dupouy; 🇫🇷 Argenteuil, Val d'Oise, France