Pharmacokinetic Study on Echinocandins for Patients With Septic Shock Following Secondary Peritonitis (EPI Study)

The secondary objectives of this study are:

* Determine whether the current recommended doses of caspofungin achieve the Pharmacokinetic/Pharmacodynamic (PK/PD) target for this molecule.
* Determine whether the current recommended doses of micafungin achieve the PK / PD target for this molecule
* Describe the peritoneal concentrations of echinocandins in secondary peritonitis complicated with septic shock
* Identify via modeling PK / PD parameters and based on monte Carlo simulations the optimal dosing regimen for caspofungin and micafungin in this population

• Echinocandins (Drug), also known as caspofungin or micafungin: The patients included in this protocol require routine treatment with caspofungin or micafungin. Though this intervention is under study, it is not modified by this protocol.

Primary outcomes

• Antifungal treatment plasmatic clearance (L/h) [Day 1]
• Antifungal treatment plasmatic clearance (L/h) [Days 3-5]
• The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration [Day 1]
• The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration [Days 3-5]
• Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration [Day 1]
• Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration [Days 3-5]
• The area under the curve for plasmatic antifungal treatment concentrations [Day 1]
• The area under the curve for plasmatic antifungal treatment concentrations [Days 3-5]
• The maximum concentration for plasmatic antifungal treatment concentrations [Day 1]
• The maximum concentration for plasmatic antifungal treatment concentrations [Days 3-5]
• The minimum concentration for plasmatic antifungal treatment concentrations [Day 1]
• The minimum concentration for plasmatic antifungal treatment concentrations [Days 3-5]

Secondary outcomes

• The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin [Day 1]: corresponds to: area under the curve / minimum inhibitory concentration >865
• The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin [Days 3-5]: corresponds to: area under the curve / minimum inhibitory concentration >865
• The target Pharmacokinetic/Pharmacodynamic ratio for micafungin [Day 1]: corresponds to: area under the curve / minimum inhibitory concentration >285 et 3000
• The target Pharmacokinetic/Pharmacodynamic ratio for micafungin [Days 3-5]: corresponds to: area under the curve / minimum inhibitory concentration >285 et 3000
• The area under the curve for peritoneal antifungal treatment concentrations [Day 1]
• The area under the curve for peritoneal antifungal treatment concentrations [Days 3-5]
• The maximum concentration for peritoneal antifungal treatment concentrations [Day 1]
• The maximum concentration for peritoneal antifungal treatment concentrations [Days 3-5]
• The minimum concentration for peritoneal antifungal treatment concentrations [Day 1]
• The minimum concentration for peritoneal antifungal treatment concentrations [Days 3-5]
• The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Day 1]
• The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Days 3-5]
• The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Day 1]
• The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Days 3-5]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* The emergency inclusion procedure was correctly applied according to French law (signature of consent form by a patient-designated trusted person or a family member, or a medical decision to proceed with patient inclusion if the latter two persons are unavailable) ---- OR ---- signature of the consent form by the patient
* The patient must be insured or beneficiary of a health insurance plan
* The patient is 18 years of age or older
* The patient has beed admitted to the ICU for septic shock accompanying secondary peritonitis
* Patient requiring antifungal treatment via echinocandins (caspofungin or micafungin)
* A venous or arterial access for blood sampling is already in place for routine care

Exclusion Criteria:

* The patient is participating in an interventional study that may affect the results of the present study, or has participated in such a study within the past 3 months
* The patient is under judicial protection, or is an adult under guardianship
* The patient is pregnant, parturient or breastfeeding
* Moribund patient
* Known positive serology for human immunodeficiency virus (HIV)
* Known positive serology for hepatitis C
* Known diagnosis for tuberculosis

• Results publication: Garbez N, Mbatchi L, Wallis SC, Muller L, Lipman J, Roberts JA, Lefrant JY, Roger C. Prospective Cohort Study of Micafungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-abdominal Infections. Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0230720. doi: 10.1128/AAC.02307-20. Epub 2021 Jun 17. PMID 33846133

• Claire Roger, MD, Principal investigator, Centre Hospitalier Universitaire de Nīmes

NIH grants: 2016