Target

Therapeutic Drug Monitoring for Piperacillin/Tazobactam

Administration of antibiotics active against the infecting organism is a cornerstone of effective sepsis management. Management is however complicated by increasing antimicrobial resistance with shortage of new antimicrobial substances. Given the paucity of new antibacterial agents to optimize antimicrobial use and bring out the best of the currently available agents is indispensable. Increasing evidence indicates however that antibiotic dosing in critically ill patients is inadequate with fixed-dose regimens. Pharmacokinetic (PK) and pharmacodynamic (PD) studies during pharmaceutical registration trials are usually conducted in healthy, normal weighted young adults in most instances. However, critically ill patients have a gross physiological derangement, which profoundly impacts PK. Patients with sepsis are known to become hyperdynamic, causing increased clearance of ß-lactams; end-organ dysfunction can lead to impaired drug clearances and capillary leak syndrome results in increased interstitial fluid volumes. Inadequate concentrations, however, negatively affect infection-related patient outcomes and promote the development of antibiotic resistance. Methods to optimize administration of ß-lactam antibiotics in these patients are urgently required. Hence, the primary study goal is to investigate whether a therapeutic drug monitoring (TDM) - based dose optimization of piperacillin positively affects outcome in patients with severe sepsis or septic shock.