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

Not Applicable

Completed

• Conditions: Community-acquired Pneumonia; Amoxicillin; Empyema; Pharmacokinetic; Pleural Infection
• Interventions: Procedure: chest tube drainage; Biological: antibiotic concentration in pleural fluid; Drug: Amoxicillin + clavulanic acid

• Registration Number: NCT04350502
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

Brief Summary

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

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.

Study Timeline

• Study Start: 2020-04-04
• Study First Submitted: 2020-04-09
• Study First Submitted QC: 2020-04-16
• Study First Posted: 2020-04-17
• Status Verified: 2023-09
• Primary Completion: 2023-09-12
• Study Completion: 2023-09-12
• Last Update Submitted: 2023-09-12
• Last Update Posted: 2023-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
complicated pleural infection patients	Amoxicillin + clavulanic acid	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
complicated pleural infection patients	antibiotic concentration in pleural fluid	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
complicated pleural infection patients	chest tube drainage	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

Primary Outcome Measures

Name	Time	Method
Area Under the Pleural Concentration Versus Time Curve (AUC) of "amoxicillin and clavulanic acid"	up to 72 hours after starting chest pleural drainage	Area Under the Pleural Concentration Versus Time Curve (AUC) of "amoxicillin and clavulanic acid" in patients with a complicated pleural infection

Trial Locations

Locations (1)

CHU Amiens; 🇫🇷 Amiens, France