Pharmacokinetic and pharmacodynamic target attainment of amoxicillin(-clavulanic acid) in pleural empyema fluid and complicated parapneumonic effusion

Rationale: Pleural empyema has a high morbidity and mortality rate, for which timely and adequate treatment is of paramount importance. Unfortunately, to date the optimal antibiotic treatment in terms of dose, duration and route of administration is still subject of debate. Pleural empyema and complicated parapneumonic effusions are treated with prolonged intravenous antibiotic treatment. However, the evidence for and specifications of these recommendations are lacking, leading to inconsistent treatment policies between practitioners and possibly unnecessary patient exposure to the risks of prolonged parenteral antibiotics and prolonged hospitalization. As a prerequisite for recommendations regarding the dose, duration and route of administration, we should first establish whether the current recommended antibiotic agents achieve adequate drug levels at the site of infection to effectively kill the pathogen, by investigating whether the pharmacokinetic and pharmacodynamic target is attained in pleural effusion/empyema.

Objective: To determine the exposure of IV amoxicillin(-clavulanic acid) in pleural empyema fluid or complicated parapneumonic effusion and to assess the probability of PK/PD target attainment in the pleural fluid of patients diagnosed with pleural empyema or complicated parapneumonic effusion, with the currently recommended dosing regimens for the most commonly isolated pathogens

Study design: Prospective, observational study.

Study population: Hospitalized non-critically ill patients diagnosed with pleural empyema or complicated parapneumonic effusion, who are treated with antibiotics and chest tube drainage, with or without flushing.

Intervention: A maximum of 8 blood plasma samples and 12 pleural fluid samples will be collected.

Main study parameters/endpoints: Endpoints are the probability of target attainment in pleural fluid of intravenous amoxicillin(-clavulanic acid) and the penetration ratio of the antibiotics from blood plasma to pleural fluid, expressed as the fAUC0-6/8 of pleural fluid divided by the fAUC0-6/8 of plasma.

To determine the exposure of IV amoxicillin(-clavulanic acid) in pleural empyema fluid or complicated parapneumonic effusion and to assess the probability of PK/PD target attainment in the pleural fluid of patients diagnosed with pleural empyema or complicated parapneumonic effusion, with the currently recommended dosing regimens for the most commonly isolated pathogens

Patients will have one or two study visits, depending on