Predictive Factors of Good Pulmonary Penetration of Antibiotics : AntiBiotics Dosage in Broncho-Alveolar Lavage

Study Overview
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Brief Summary
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Respiratory infections are common and sometimes very severe. An insufficient dosage of the antibiotic could lead to a treatment failure A correct plasmatic antibiotic concentration is not a guarantee of a clinical success as it could not be a reflect of pulmonary concentration. The aim of this study is to determinate the predictive factors of pulmonary penetration of antibiotics in patients with a beta lactamines failure and who undergoes a flexible bronchoscopy.

Detailed Description
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To check if pulmonary concentrations of antibiotic are enough we will measure antibiotic concentration in the broncho-alveolar lavage (BAL). This technique which is clinically relevant and reliable could determinate the pulmonary diffusion level for antibiotics by calculating the ratio between plasmatic and intra-alveolar antibiotic concentration. This ratio will be correlated with potential limitation factors of pulmonary diffusion as respiratory diseases (COPD, cystic fibrosis, fibrosis…), sepsis, hypoalbuminemia. We have chosen to study the beta lactamin antibiotics because they are the most frequently used in pneumonia. Moreover, the beta lactamins pulmonary diffusion is likely to be the lowest. Finally, for patients with a known pathogen, we will divide this pulmonary concentration with minimal inhibitory concentration (MIC). Indeed, in severe pneumonia, to be sure of bactericidal activity, a pulmonary concentration of beta lactamines should be always higher than 4 to 5 times MIC.

Official Title
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Predictive Factors of Good Pulmonary Penetration of Antibiotics : AntiBiotics Dosage in Broncho-Alveolar Lavage

Conditions
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Antibiotics, Pneumonia

Intervention / Treatment
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* Biological: measure of intra-alveolar antibiotic concentration in µg/ml
* Procedure: broncho-alveolar lavage (BAL)
* Biological: blood test to measure plasmatic antibiotic concentration in µg/ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who undergo a flexible bronchoscopic lavage and with a beta lactamines treatment as cephalosporin of 3rd generation (CEFTRIAXONE / CEFOTAXIME, CEFTAZIDIME), of 4th generation (CEFEPIM), or AMOXICILLIN-CLAVULANIC ACID, or PIPERACILLIN-TAZOBACTAM patient major informed and signed consent form Exclusion Criteria: patient under chronic dialysis patient placed under judicial protection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: measure of intra-alveolar antibiotic concentration in µg/ml|included patients will have a broncho-alveolar lavage (BAL) to measure intra-alveolar antibiotic concentration, and a blood test to measure plasmatic concentration|
|Procedure: broncho-alveolar lavage (BAL)|included patients will have a broncho-alveolar lavage (BAL) to measure intra-alveolar antibiotic concentration, and a blood test to measure plasmatic concentration|
|Biological: blood test to measure plasmatic antibiotic concentration in µg/ml|included patients will have a broncho-alveolar lavage (BAL) to measure intra-alveolar antibiotic concentration, and a blood test to measure plasmatic|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary diffusion level for beta lactamins | pulmonary diffusion level for beta lactamins is determined by ratio between bronchoalveolar concentration and plasmatic concentration of tested antibiotics | on the day of the bronco-alveolar lavage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measure of apyrexia duration in days | measure of apyrexia duration in days | from day of inclusion to 15 days after inclusion | 
| duration in days for regression of the biological inflammatory syndrome | duration in days for regression of the biological inflammatory syndrome (CRP concentration in mg/l divided by 2) | from day of inclusion to 15 days after inclusion | 
| measure of length of hospitalisation | measure of length of hospitalisation in days | from day of inclusion to 15 days after inclusion | 
| Number of deaths at 28-day | 28-day mortality will be measured | 28 days after inclusion | 
| virus presence in BAL | virus presence will be detected in bronchoalveolar lavage (BAL) | day of bronchoalveolar lavage (BAL) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotics, Pneumonia, broncho-alveolar lavage