Population Pharmacokinetic Modeling to Optimize the Dosage of the Piperacillin / Tazobactam Combination in Patients With Sepsis in Intensive Care

Population pharmacokinetic modeling mathematically describes the pharmacokinetics of a drug and the variables likely to influence it in a "typical" patient population. We propose to model a Bayesian estimator, taking into account the individual factors that influence exposure to the piperacillin / tazobactam combination in a target population of sepsis, to allow for early assessment of serum Piperacillin / Tazobactam concentration profiles. optimization of dosing regimens. Indeed, pharmacokinetic tools of this type are already regularly successfully applied for other classes of antibiotics or immunosuppressants whose therapeutic index is narrow. They reduce the toxic risk and optimize the effectiveness of these treatments.

Inclusion Criteria: * Major patient (age ≥18 years) male or female. * Patient hospitalized in intensive care for sepsis, involving (i) a suspected or proven infection; (ii) a systemic inflammatory response; (iii) dysfunction of at least one organ, according to the international consensus "sepsis-3". * Patient with an arterial catheter that can be used for blood sampling by the time the first dose of piperacillin / tazobactam is administered. * Patient for whom treatment with piperacillin / tazobactam, alone or in combination with another antibiotic, is prescribed according to the following modalities (drug SPC): scheduled antibiotic treatment for at least 48 hours in IV infusion of 4 g of piperacillin and 0.5 g tazobactam over 3 hours, every 6 hours or every 8 hours. * Patient affiliated to a social security scheme. * Patient informed and given his non-opposition. If the patient is unable to do so (emergency situations) the non-opposition will be obtained from the patient's representative. Exclusion Criteria: * Treatment with piperacillin and / or tazobactam within 7 days prior to evaluation. * Patient with a history of allergy to penicillins or β-lactams. * Kidney function of Kdigo score = 3 (3 times baseline plasma creatinine or plasma creatinine ≥ 354μmol / L or extra-renal clearance, or diuresis \