[Pharmacokinetics and therapeutic monitoring of piperacillin/tazobactam].

Abstract

Given their wide therapeutic index, beta-lactam antibiotics are commonly used to treat critically ill patients. It is in these patients that significant heterogeneity in pharmacokinetics was noted, compared to the population average, especially in the volume of distribution, drug clearance and biological half-life, with values increasing as much as two-fold or, in the case of biological half-life, as much as four-fold. Significant pharmacokinetic changes also occur in cases of morbid obesity or renal insufficiency and when complex surgical techniques such as extracorporeal circulation are used. Therapeutic monitoring of piperacillin/tazobactam is a way to personalize and optimize therapy for these groups of patients. Preclinical data show a correlation between the probability of therapeutic success and concentrations of the unbound fraction of an antibiotic exceeding the minimum inhibitory concentration (MIC) for 40-50 % of the dosing interval. This time appears to be the preferred pharmacodynamic target for beta-lactam antibiotics. In critically ill patients, however, an even higher target may be required, ideally 100 % fT > 4xMIC. A better pharmacodynamic profile can be obtained using prolonged or continuous infusion. The biggest obstacle to routine TDM in β-lactams is the speed of quality sample determination. Currently, the most widely used method of measuring plasma concentrations is liquid chromatography coupled with UV or MS detection.