Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

Assistance Publique - Hôpitaux de Paris70 enrolled

Overview

The study is a prospective open trial conducted in 4 centers, and designed to determine if pharmacokinetic (PK) and pharmacodynamic (PD) parameters of imipenem, associated with amikacin as empirical therapy, impact microbiological and clinical outcome of patients with Gram negative bacilli (GNB) ventilator-associated pneumonia (VAP).

Inappropriate initial antibiotherapy increases mortality of many serious infections. This is the case for ventilator-associated pneumonia, frequently occurring during intensive care unit (ICU) hospitalization, and whose 48 first hours of treatment are decisive. It is well established that pharmacokinetic and pharmacodynamic parameters of antibiotics are correlated with their clinical and microbiological effectiveness. However in ICU patients, pharmacokinetic parameters of antibiotics suffer great variations, and bacteria responsible for these infections are usually less sensitive to antibiotics, especially Gram negative bacilli (GNB). An important pharmacodynamic variability may occur at the initial phase of the antibiotic treatment, decisive for the infection's outcome. We propose to evaluate the correlation between pharmacokinetic and pharmacodynamic profile of the empirical antibiotic therapy and the microbiological and clinical outcome of VAP.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ventilator Associated Pneumonia

Interventions

Imipenem/AmikacinDRUG

patients will received as empirical therapy for VAP imipenem associated with amikacin.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years 2. Mechanical ventilation for more than 48 hours 3. Clinical suspicion of VAP defined by a new persistent radiological infiltrate and one of the following signs: purulent tracheal aspirations, or temperature of 38°3 or higher, or leucocyte count \> 10000/ml 4. Risk of multi resistant bacteria defined as follows: at least 6 days of mechanical ventilation or antibiotic treatment in the 15 previous days 5. Distal pulmonary secretion sample obtained beforehand for microbiological diagnosis by bronchoalveolar lavage via bronchoscopy or blinded protected telescoping catheter via bronchoscopy or blindly 6. Presence of GNB on direct examination of the distal pulmonary secretion sample 7. Realization of a preliminary medical examination. 8- Written inform consent from the patient or relatives. The consent may be obtained after the enrollment if the patient is not able to give consent and if there is no relatives Exclusion Criteria: 1. Time between distal pulmonary secretion sample taking and the 1st administration of imipenem exceeding 24 hours 2. Pregnancy 3. Severely impaired renal function (creatinine clearance lower than 10 mL/mn or renal replacement therapy) 4. Allergy to imipenem or amikacin 5. Treatment in progress with imipenem or amikacin 6. Death expected within 48 hours following diagnosis of VAP 7. Myasthenia 8. Simultaneous administration of others aminoglycosides 9. Association with intravenous polymyxin or botulinum toxin

Locations (1)

Victor Dupouy Hospital

Argenteuil, France

Outcomes

Primary Outcomes

Variation of numeration (cfu per ml) of GNB, for whom culture of pulmonary samples are positive (higher than defined thresholds), between the quantitative endotracheal aspiration (QAE) obtained at H0 (initiation of treatment) and QAE obtained at H48

Time frame: Hour 48

Secondary Outcomes

To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP

Time frame: Hour 24

To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP

Time frame: Hour 24

To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved

Time frame: Hour 24

To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP

Time frame: Hour 24

To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3

Time frame: Day 3

To assess the impact of imipenem and amikacin PK/PD parameters variability on the CPIS, clinical score of VAP, measured 48 hours after initiation of the treatment

Time frame: Hour 48

To assess the impact of imipenem and amikacin PK/PD parameters on the time necessary to observe a CPIS lower or equal to 6

Time frame: Day 8

To assess the impact of imipenem and amikacin PK/PD parameters on clinical evolution of the VAP after 7 days of antibiotic treatment

Data from ClinicalTrials.gov

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