Drug Clearance After Severe Burn Injury
Conditions
Keywords
burns, cefiderocol, pharmacokinetics, pharmacodynamics, augmented renal clearance, Gram-negative bacterial infections
Brief summary
Cefiderocol is a powerful, broad spectrum antibiotic approved to treat hospital-acquired or ventilator associated pneumonia and urinary tract infections. Although cefiderocol has labeled dosing recommendations, including augmented renal clearance, patients with burn injury remain an unstudied population at high risk for MDR pathogens. The primary objective of this study is to evaluate the pharmacokinetic principles of cefiderocol in patients after acute burn injury. Findings from this study will determine the dose and interval necessary to maintain therapeutic concentrations of cefiderocol in patients after burn injury for adequate bactericidal activity, prevention of resistance, and treatment outcomes.
Detailed description
Twelve patients with burn injuries will be enrolled after written consent is obtained. Six interval-specific samples will be drawn from each patient, depending on the dosing regimen chosen. Inclusion Criteria: 1) age ≥ 18 and ≤ 80 years old, 2) estimated CLCR (eCLCR) ≥ 60 mL/min via Cockcroft-Gault equation Exclusion Criteria 1\) KDIGO classification ≥ 1 at day of screening, 2) known HIV or HBV infection Non-compartmental modeling via WinNonlin and Monte Carlo simulation will be used to determine the probability of cefiderocol dosing regimens achieving the fT\>MIC threshold for P.aeruginosa. Safety monitoring for adverse events will occur daily up to and through the sampling period.
Interventions
DRUGCefiderocol
Cefiderocol will be prescribed according to indication and estimated renal function as either 2g over 3 hours dosed either every 6 or 8 hours.
Sponsors
University of Tennessee
Shionogi Inc.
Regional Medical Center, Regional One Health
Center for Anti-Infective Research and Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* age ≥ 18 and ≤ 80 years old * estimated CLCR (eCLCR) ≥ 60 mL/min via Cockcroft-Gault equation
Exclusion criteria
* KDIGO classification ≥ 1 at day of screening * known HIV or HBV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Appropriateness of package insert-stated dosing regimens | through study completion, an average of 3 days | Steady state blood samples will be collected and analyzed to establish concentration time profiles. Models will be established using body size, renal function, and severity of injury. Dosing regimens will be constructed and tested via Monte Carlo simulation to determine the probability of cefiderocol regimen achieving the fT\>MIC threshold for P.aeruginosa at 75% and 100% fT\>MIC. |
Countries
United States
Outcome results
None listed