Pharmacokinetics and Pleural Fluid Penetration of Amoxicillin and Clavulanic Acid in Patients With Pleural Infections

Study Overview
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Brief Summary
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The incidence of pleural infection is increasing worldwide since the last two decades. Antibiotics are one of the cornerstones of the treatment of this disease and must be associated to a correct evacuation of the pleural effusion. Data concerning the pleural diffusion of antibiotics currently used in community acquired pleural infection are scarce. The main objective of this study is to evaluate the pleural pharmacokinetic of amoxicillin and clavulanic acid in patients with a complicated pleural infection (patients who need a chest tube insertion).

Detailed Description
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Only scarce data are known on the pleural diffusion of antibiotics. Most of these data are concerning antibiotics that are not commonly used for the treatment of community-acquired pleural infections. Moreover, these data are obtained from studies using heterogenous methodologies (single or repeated evaluation of the antibiotic concentration in the pleural effusion, with or without correlation to the serum concentration; animal model or very specific population (i.e. uninfected patients or following lung surgery). The main objective of this study is to evaluate the pleural pharmacokinetic of amoxicillin and clavulanic acid in patients with a community-acquired complicated pleural infection. Patients with a complicated pleural infection will be managed according to the French guideline with a chest tube drainage associated to a treatment with amoxicillin (2g*3 by day) and clavulanic acid (200mg*3 by day). Repeated samples of pleural fluid and serum will be taken to evaluate antibiotics' concentrations at H0; H½; H1; H2; H3; H4; H8 and H24. The follow-up and management of the included patients will not be modified by the study protocol except for the pleural and serum samples. Clinical, biological and radiological (chest x-ray and/or thoracic ultrasound) evaluation will be performed daily. Success of the pleural drainage will be assessed at day 3.

Official Title
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Pharmacokinetics and Pleural Fluid Penetration of Amoxicillin and Clavulanic Acid in Patients With Pleural Infections

Conditions
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Pharmacokinetic, Amoxicillin, Pleural Infection, Empyema, Community-acquired Pneumonia

Intervention / Treatment
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* Procedure: chest tube drainage
* Biological: antibiotic concentration in pleural fluid
* Drug: Amoxicillin + clavulanic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all adult patients (≥ 18 years old) hospitalized for a complicated community acquired pleural infection at University Hospital Amiens-Picardie. Complicated pleural infection is defined by the presence of one of the following criteria: frank pus, loculated pleural fluid, presence of organisms identified by Gram stain and/or culture from a non-purulent pleural fluid sample, pleural fluid pH <7.2, pleural fluid glucose <0.32g/l or large non-purulent effusion. Exclusion Criteria: non-infectious pleural effusion hospital-acquired pleural infection patient treated with amoxicillin and clavulanic acid (if treatment was started more than > 24h ago) Minors, pregnant women, adult patients protected by law. Pleural infection requiring instant thoracic surgery allergy to beta-lactam Injection of contrast agent (Iomeron or Iohexol) during the 24 hours preceding or following the first dose of amoxicillin / clavulanic acid.

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: complicated pleural infection patients<br>Patients with a complicated pleural infection will be managed according to the French guideline with a chest tube drainage associated to a treatment with amoxicillin (2g*3 by day) and clavulanic acid (200mg*3 by day). Repeated samples of pleural fluid and serum will be taken to evaluate antibiotics' concentrations at H0; H½; H1; H2; H3; H4; H8 and H24 | Procedure: chest tube drainage<br>* Patients with a complicated pleural infection will be managed according to the French guideline with a chest tube drainage associated to a treatment with amoxicillin (2g*3 by day) and clavulanic acid (200mg*3 by day).<br>Biological: antibiotic concentration in pleural fluid<br>* Patients with a complicated pleural infection will be managed according to the French guideline with a chest tube drainage associated to a treatment with amoxicillin (2g*3 by day) and clavulanic acid (200mg*3 by day). Repeated samples of pleural fluid and serum will be taken to evaluate antibiotics' concentrations at H0; H½; H1; H2; H3; H4; H8 and H24<br>Drug: Amoxicillin + clavulanic acid<br>* Patients with a complicated pleural infection will be managed according to the French guideline with a chest tube drainage associated to a treatment with amoxicillin (2g*3 by day) and clavulanic acid (200mg*3 by day). Repeated samples of pleural fluid and serum will be taken to evaluate antibiotics' concentrations at H0; H½; H1; H2; H3; H4; H8 and H24<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Pleural Concentration Versus Time Curve (AUC) of amoxicillin and clavulanic acid | Area Under the Pleural Concentration Versus Time Curve (AUC) of amoxicillin and clavulanic acid in patients with a complicated pleural infection | up to 72 hours after starting chest pleural drainage | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pleural Infection, Empyema, Community-acquired Pneumonia, amoxicillin, clavulanic acid, pneumococcal antigen, pharmacokinetic