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

NCT ID: NCT07167524

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2028-04-01

Brief Summary

Severe bacterial infections, often responsible for sepsis and septic shock, are a major challenge in critical care: approximately 50% of patients are affected, with a mortality rate of up to 40%. Their initial management consists of antibiotic therapy with an adapted spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumopathies, intra-abdominal infections, urinary tract infections, etc.). Mortality rates of up to 40%. Their initial management consists of antibiotic therapy with an appropriate spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumonia, intra-abdominal infections, urinary tract infections, etc.).

Intensive care patients with septic shock exhibit specific pharmacokinetics with an increased volume of distribution, notably due to significant capillary leakage, often disrupted hepatic metabolism, possible hypoalbuminemia, the presence of renal hyperclearance in the initial phase or conversely, the onset of renal failure with altered glomerular filtration rate, sometimes leading to extrarenal clearance, changes that have consequences for the efficacy and toxicity of the administered antibiotic therapy. Sepsis itself also causes renal dysfunction, with the main pathophysiological hypotheses being an alteration of microcirculation, cellular metabolic reprogramming, and deregulation of the inflammatory response. It is therefore essential to focus on the dosages administered and the pharmacokinetics of these patients. Indeed, underdosing is associated with the emergence of resistance and a poorer prognosis in intensive care patients: increased risk of treatment failure, length of stay and mortality. Conversely, significant overdoses can be associated with a poorer renal prognosis, seizures, encephalopathy which can lead to delayed awakening, prolonged duration of mechanical ventilation and intensive care stay.

Detailed Description

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.

Conditions

Sepsis; Severe Bacterial Infections

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

Dosage concentration of piperacillin and tazobactam

The concentration of piperacillin and tazobactam will be quantified by liquid chromatography coupled with tandem mass spectrometry (HPLC-MS² - CIC-CRB 1404) at each of these times by transposition of the method already used in current practice.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Rouen Hospital

Rouen, , France

Countries

France

Central Contacts

Camille CR RENARD, Doctor

Role: CONTACT

Domitille.Renard@chu-rouen.fr

02 32 88 33 27 ext. +33

Facility Contacts

Domitille DR RENARD, Doctor

Role: primary

Domitille.Renard@chu-rouen.fr

02 32 88 33 27 ext. +33

Other Identifiers

2025-A00885-44

Identifier Type: OTHER

Identifier Source: secondary_id

2023/0306/OB

Identifier Type: -

Identifier Source: org_study_id