Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

NCT ID: NCT00950222

Last Updated: 2012-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2012-01-31

Brief Summary

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).

Detailed Description

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.

Conditions

Ventilator Associated Pneumonia

Keywords

Intensive care unit; Ventilator associated pneumonia; Gram negative bacilli infection; Empirical antibiotic therapy; Pharmacokinetic / pharmacodynamic; Imipenem; Amikacin; Gram negative bacilli

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1:Imipenem/Amikacin

patients will receive as empirical therapy for VAP imipenem associated with amikacin.After primary outcome measure, antibiotic therapy will be left at the discretion of the physician in charge of the patient.

Imipenem: recommended usual dosage for VAP treatment, IV (in the vein), every 8 hours

Amikacin: recommended usual dosage for VAP treatment (20mg/kg), IV (in the vein), single dose (at H0) for the 48 first hours of treatment

Group Type: EXPERIMENTAL

Imipenem/Amikacin

Intervention Type: DRUG

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

Interventions

Imipenem/Amikacin

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

Intervention Type: DRUG

Other Intervention Names

Therapy for VAP imipenem associated with amikacin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier PAJOT, MD

Role: PRINCIPAL_INVESTIGATOR

HOPITAL ARGENTEUIL

Locations

Victor Dupouy Hospital

Argenteuil, , France

Countries

France

References

Burdet C, Pajot O, Couffignal C, Armand-Lefevre L, Foucrier A, Laouenan C, Wolff M, Massias L, Mentre F. Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. Eur J Clin Pharmacol. 2015 Jan;71(1):75-83. doi: 10.1007/s00228-014-1766-y. Epub 2014 Oct 21.

Reference Type: DERIVED

PMID: 25327505 (View on PubMed)

Couffignal C, Pajot O, Laouenan C, Burdet C, Foucrier A, Wolff M, Armand-Lefevre L, Mentre F, Massias L. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens. Br J Clin Pharmacol. 2014 Nov;78(5):1022-34. doi: 10.1111/bcp.12435.

Reference Type: DERIVED

PMID: 24903189 (View on PubMed)

Other Identifiers

CRC06049

Identifier Type: OTHER

Identifier Source: secondary_id

P061014

Identifier Type: -

Identifier Source: org_study_id