Abdominal Surgery Patients, Candida, Critically Ill Intensive Care Unit Patients, Intra-Abdominal Infection
Conditions
Keywords
candida, intra-abdominal candidiasis, abdominal surgery, pharmacokinetics, pharmacodynamics
Brief summary
ntra-abdominal candidiasis is a serious infection common in critically ill patients, often leading to high mortality if not treated quickly. Standard antifungal treatments may be less effective due to growing resistance and poor drug penetration into the abdominal cavity. In critically ill patients, drug levels can vary widely due to factors like surgery, inflammation, fluid resuscitation, or extracorporeal support, increasing the risk of underdosing. Rezafungin is a new antifungal agent with a long half-life and broad activity against Candida species, offering potential advantages in this setting. However, there is currently no data on its concentration or effectiveness in the peritoneal fluid of patients with intra-abdominal sepsis. Its long half-life, coupled with repeated pharmacokinetic variations in critical care settings and the risk of insufficient concentrations, may hinder its use in this population.
Interventions
None listed
Sponsors
Central Hospital, Nancy, France
Mundipharma Research GmbH & Co KG
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age \> 18 years * with a suspected intra-abdominal candidiasis requiring abdominal surgery * and receiving the administration of rezafungin as first-line empirical antifungal treatment just before or within 1 hour the abdominal surgery * and having abdominal drain for at least 2 days after the surgery
Exclusion criteria
* death expected within 24h * decline to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peritoneal/Plasma Penetration Ratio of Rezafungin | From 0 to 3 hours after rezafungin administration | Penetration ratio of rezafungin will be calculated as the ratio of the area under the concentration-time curve from 0 to 3 hours (AUC₀-₃h) in peritoneal fluid compared to plasma in critically ill patients undergoing abdominal surgery for suspected or proven intra-abdominal candidiasis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration-Time Profile of Rezafungin | From 0 to 168 hours after the first rezafungin administration | Area under the concentration-time curve (AUC) of rezafungin in plasma will be calculated over three time intervals: AUC₀-₂₄h, AUC₀-₄₈h, and AUC₀-₁₆₈h to describe the evolution of plasma concentrations during treatment |
| Peritoneal Concentration-Time Profile of Rezafungin | From 0 to 48 hours after the first rezafungin administration | Area under the concentration-time curve (AUC) of rezafungin in peritoneal fluid will be calculated over two time intervals: AUC₀-₂₄h and AUC₀-₄₈h to describe the evolution of peritoneal concentrations during treatment. |
| Target Attainment in Peritoneal Fluid at the Time of Surgery | At the time of abdominal surgery (within the first 3 hours after rezafungin administration) | Proportion of patients achieving the pharmacodynamic target in peritoneal fluid, defined as AUC₀-₃h / MIC \> 40, measured at the time of surgery. |
| Postoperative Target Attainment in Plasma | From 0 to 168 hours after the first rezafungin administration | Proportion of patients achieving the pharmacodynamic target in plasma, defined as AUC₀-₁₆₈h / MIC \> 40 |
| Factors Associated with Target Attainment in Peritoneal Fluid | From 0 to 48 hours after the first rezafungin administration | Analysis of clinical and biological covariates associated with pharmacokinetic variability and the achievement of pharmacodynamic targets in peritoneal fluid |
| Association Between Pharmacodynamic Target Attainment and Day-28 In-Hospital Mortality | From rezafungin administration to Day 28 post-treatment | Comparison of Day-28 in-hospital mortality rates between patients who did and did not achieve pharmacodynamic targets in plasma and/or peritoneal fluid |
Countries
France
Contacts
CONTACTEmmanuel NOVY, MD, PhD
Outcome results
None listed