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

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

Study 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.

Eligibility

Primary outcome measure(s)

• Determination of continuous extrarenal clearance (CERC) of piperacillin in patients with infection in intensive care — At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
  The cERC clearance of piperacillin will depend on the type of cERC used, thus determining a clearance: * diffusion (dialysis, continuous venomous hemodialysis (CVVHD)), * convection (filtration, continuous venomous hemofiltration (CVVH)), * diffusion and convection (dialysis and filtration, continuous venomous hemodiafiltration (CVVHDF)). Each of these clearances will be characterized by different formulas, based on the collection of the following parameters: pre- and post-filter concentrations, concentration in the dialysate/filtrate/effluent, cERC flow rate for diffusion and convection, hematocrit, and partition coefficient of the substance between whole blood and plasma.

Trial sites (1)

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