Pharmacokinetics and Pleural Fluid Penetration of Amoxicillin and Clavulanic Acid in Patients With Pleural Infections (PK-plèvre)

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).

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80480
    • CHU Amiens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: complicated pleural infection patients; 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; 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).; Biological: 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; Drug: 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens
• Investigators: Principal Investigator: Damien BASILLE, MD, CHU Amiens

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2019
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetic; amoxicillin; clavulanic acid; Community-acquired Pneumonia; Pleural Infection; Empyema; pneumococcal antigen
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Inflammation; Pneumonia; Suppuration; Pathological Conditions, Signs and Symptoms; Community-Acquired Infections; Empyema; Community-Acquired Pneumonia; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Amides; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Clavulanic Acid; Clavulanic Acids; Ampicillin; Penicillins; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: PI2019_843_0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No