PK/PD of High Dose Pip/Tazo in Obese Patients

Worldwide rates of obesity have doubled in the last 30 years, and obesity has been associated as a risk factor for hospital-acquired infections and increased occurrence of death in critically-ill patients. Piperacillin/tazobactam is a commonly prescribed antibiotic for critically ill patients with an infection, however, limited information exists for dosing this drug in obese patients. In these limited reports, standard doses of piperacillin/tazobactam given to the small number of obese patients resulted in lower blood concentrations, which could lead to inadequate killing of bacteria. The purpose of this study is to compare blood concentrations from standard piperacillin/tazobactam dosing compared to higher dosing regimens in obese patients. This study will also include information on the safety and tolerability of the higher dose regimens. The study investigators believe that the higher dosing regimen will produce adequate blood levels in obese patients and will not add any more risk of harm to obese patients receiving this higher dose.

pharmacokinetics, obesity, piperacillin-tazobactam combination product, pharmacodynamics, piperacillin/tazobactam

Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Then, they will be switched to higher dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared.

Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Patients will be switched to higher dose after receiving the standard dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared.

Pharmacokinetic parameters for piperacillin of maximum serum concentration (Cmax) will be measured in both standard dosing and high dosing.

Half-life (t1/2) of piperacillin will be calculated from serum concentrations in both standard and high doses

Volume of distribution (Vd) of piperacillin will be calculated from serum concentrations in both standard and high doses

Inclusion Criteria: BMI greater than or equal to 30 kg/m2 Weight at least 105 kg Age 18-89 years of age Prescribed piperacillin/tazobactam at standard doses for suspected or confirmed infection(s) English or Spanish speaking Central line access Exclusion Criteria: Do not meet specified inclusion criteria Hepatic impairment classified by Child-Pugh Class B or greater Documented pre-existing seizure disorder Documented pre-existing hematologic disorder Pregnancy Documented allergy or contraindication to beta-lactams or tazobactam

Veillette JJ, Winans SA, Maskiewicz VK, Truong J, Jones RN, Forland SC. Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin-Tazobactam in Obese Patients. Eur J Drug Metab Pharmacokinet. 2021 May;46(3):385-394. doi: 10.1007/s13318-021-00677-1. Epub 2021 Mar 20.