Evaluation of the Dialytic Clearance of the Combination of Peracillin and Tazobactam

Pip-taz is administered intravenously due to non-absorption via the oral route. It is weakly bound to plasma proteins (21%), inducing good clearance of extrarenal clearance (fraction extracted in 4 hours: 23.6% of the administered dose). Its plasma half-life is 60 minutes. This molecule is not metabolized, and is therefore independent of liver function. It is eliminated mainly in active form in the urine (65%) and bile (35%). Thus, the main determinant of pip-taz clearance is renal clearance, or continuous extrarenal clearance (CER) in dialysis patients in intensive care.

Pip-taz is characterized by time-dependent pharmacodynamics, with better coverage with continuous infusions compared to discontinuous infusions. However, there is no well-defined pattern in patients undergoing continuous extra-renal purification. Despite recommendations regarding antibiotic dosages for use in intensive care, the lack of data regarding patients undergoing continuous renal replacement therapy (CRRE) remains a major and complex problem in optimizing treatment, as these patients present with unique pharmacokinetics, with an increased risk of treatment failure and mortality. Furthermore, there has been a change in practices in recent years, with pip-taz being administered by continuous infusion and increasingly less by discontinuous infusion, in accordance with the latest recommendations.

To our knowledge, few studies have examined the pharmacokinetics of the pip-taz combination in patients undergoing cCRRE in intensive care. Most of these rare studies did not use standard pip-taz dosages, did not examine the clinical and biological variables influencing pip-taz clearance, and none have examined the impact of any preserved diuresis. Furthermore, there are no data on the kinetics of tazobactam in this population. It therefore seems relevant, given the frequent use of this antibiotic therapy in patients undergoing cERE, to accurately assess the clearance of piperacillin and tazobactam in this population. From a precision medicine perspective, these data could contribute to the construction of a pharmacokinetic model using a population approach, based on blood, urine, and effluent samples, in order to provide a tool to assist in the prescription of this antibiotic therapy in intensive care to reduce iatrogenicity and optimize its effectiveness.

Inclusion criteria

• Adult patient over 18 years of age;
• Patient admitted to intensive care with a prescription for cREV (CVVH (pre- or post-dilution (convection)), CVVHD (diffusion), CVVHDF);
• Diagnosed or suspected infection sensitive to the piperacillin-tazobactam combination administered by continuous infusion as part of the patient's standard care;
• Concomitant prescription of piperacillin-tazobactam and cREV;
• Patient affiliated with a social security scheme;
• Adult who has read and understood the information letter and has not expressed non-opposition. Due to the potential life-threatening emergency, if the patient is unable to express their non-opposition, the consent of a trusted person or, where applicable, relatives will be sought.

Exclusion criteria

• Documented or suspected allergy to penicillins;
• Opposition from the patient or trusted person;
• Pregnant, childbirth, or breastfeeding woman;
• Minor patient;
• Person deprived of liberty by an administrative or judicial decision;
• Person placed under judicial protection, guardianship, or curatorship.