Individualized treatment for patients with parapneumonic pleural effusion via therapeutic drug monitoring and metagenomic analyses

点击翻译按钮获取中文摘要

Community acquired pneumonia is associated with high morbidity and mortality rates worldwide. It is the world’s leading infectious killer – having claimed 2.5 million lives in 2019. In contrast to tremendous advances in many areas of medicine, little progress has been achieved in pneumonia epidemiology, pathophysiology, or therapy. Accordingly, little has changed in terms of guideline recommendations in the past decades; what we accept as standard of care is often supported by low or moderate quality of evidence. Parapneumonic pleural space infections occur often and are associated with an increased mortality and a higher risk of necessitating intensive care. Current guidelines recommend ß-lactam/ß-lactamase inhibitor combinations for the treatment of this entity. However, the antibiotic pharmacokinetics data for the pleural space are scarce. We plan an in-depth pharmacokinetics characterization of both the protein-bound and free-fractions of the most often used ß-lactams in patients with parapneumonic effusions (Ampicillin/Sulbactam, Piperacillin/Tazobactam, Meropenem) in serum vs. the pleural space compartment. These data will provide much needed guidance concerning choice of antimicrobial substances with optimal penetration in the pleural compartment. Moreover, we aim to develop a prediction algorithm for the attained concentration of free, active antibiotic substance in the pleural compartment based on the trough levels in serum, which are increasingly available in the clinical routine. Such an algorithm will help individualize the dosage regimens in order to obtain optimum pharmacological exposure at the site of infection, thus reducing the risk of treatment failure due to underdosing. Lastly, we will evaluate the added diagnostic value of the 16s rRNA targeted next generation sequencing from parapneumonic pleural fluid compared to the conventional microbiological assays. These data will be further utilized as preliminary results to plan larger ‘Omics’ studies embedded in national cohorts like the Competence Network for Community Acquired Pneumonia (CAPNETZ) with the ultimate aim to attain a better epidemiologic description of this pathology. Achieving these goals would conversely provide support for the choice of empiric treatment.