S13 Antibiotic penetration into the infected pleural space; a PK/PD study

Introduction and ObjectivesPleural infection is a serious clinical condition with an average hospital length of stay of 13 days. Current standard of care defaults to hospital admission for drainage of the infected fluid and intravenous antibiotics. The standard empirical antibiotic choice varies nationally but the ability of these antibiotics to reach the pleura is poorly understood. Previous pharmacokinetics and pharmacodynamics (PK/PD) literature on the penetrance of antibiotics into pleural fluid is extrapolated from non-infected effusions (e.g. malignant effusions) or animal models.The Pleural Antibiotic Concentrations informing Treatment (PACT) study is a single centre PK/PD study that aims to assess the concentration of antibiotics within the infected pleural space to improve the evidence base around antimicrobial choice, route and duration of therapy.MethodsPatients with parapneumonic effusions/empyema planned for pleural drainage were prospectively recruited. Serial pleural fluid samples were collected timed with routine antibiotic administration and paired with synchronous serum sampling. Pleural fluid and serum antibiotic concentrations were measured using a validated high performance liquid chromatography (HPLC) method at the National Antimicrobial Reference Laboratory (Bristol UK).ResultsThis study is ongoing, further results on a wider range of antimicrobials will be available for the conference.At the time of writing, 18 patients had been recruited (15 CPPE, 3 empyema) with over 150 paired serum/fluid samples collected. Ten different antibiotics have been assayed although the majority of timepoints relate to Amoxicillin/Co-amoxiclav (n=36), Metronidazole (n=28) and Piperacillin-Tazobactam (n=22) at this time, see figure 1.Abstract S13 Figure 1Amoxicillin, Metronidazole and Tazocin (Tazobactam) levels in serum and pleural fluid post intravenous administrationFor these antibiotics the peak concentration and area under the curve within the pleural space was equivalent to serum levels. Importantly, across the dosing schedule the pleural antibiotic levels never fell below the minimum inhibitory concentrations (MICs) for bacteria known to cause pleural infection even when given orally. The pleural levels for penicillins persisted beyond the dosing schedule (8 hours) and were not affected by pleural pH or fibrinolytics.ConclusionsFor 3 commonly used antibiotics (Amoxicillin, Metronidazole, Piperacillin-Tazobactam) the pleural fluid concentration of