Surgery
Conditions
Keywords
antimicrobials, pharmacokinetics, augmented renal clearance, non critically ill
Brief summary
In this prospective observational study, the investigators want to document pharmacokinetic/pharmacodynamic (PK/PD) target attainment of frequently used antimicrobials in an adult non critically ill surgery population (abdominal surgery, traumatology and septic orthopedic surgery). Furthermore, the investigators want to identify risk factors for not attaining predefined PK/PD targets. The antibiotics of interest are amoxicillin(-clavulanic acid), flucloxacillin, piperacillin-tazobactam, meropenem and clindamycin.
Detailed description
In this research proposal, the primary objective is to describe PK parameters (area under the curve (AUC), clearance (Cl), distribution volume (Vd) and half life (T1/2)) for the antibiotics of interest (amoxicillin(-(clavulanic acid), flucloxacillin, piperacillin-tazobactam, meropenem and clindamycin) for this adult non critically ill surgery population. Besides, the investigators want to document pharmacokinetic/pharmacodynamic (PK/PD) target attainment of frequently used ABs in this population and to identify risk factors, for example augmented renal clearance (ARC), for not attaining predefined PK/PD targets.
Interventions
During one dosing interval at steady state of the involved antimicrobials (ABs), AB plasma concentrations will be determined. Besides, the measured creatinine clearance based on an 8-hour urinary collection (CrCl8h) will be used as the primary method for determining kidney function. Based on these values, CrCl8h will be calculated according to the standard formula and normalized to a body surface area (BSA) of 1.73m² .
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Every adult non-critically ill surgery patient admitted at the abdominal, trauma or septic orthopaedic surgery wards from the University Hospitals Leuven treated with multiple doses of one of the antimicrobials of interest (i.e. intravenous (IV) amoxicillin(-clavulanic acid), flucloxacillin, piperacillin-tazobactam, meropenem, oral or IV clindamycin) is eligible for inclusion.
Exclusion criteria
* age ≤ 18 years * treatment restrictions corresponding to a Do Not Reanimate code * pregnancy * lactation * renal replacement therapy * planned discharge or surgery in the coming antimicrobial dosing interval making sampling impossible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The % of time that free concentrations of antimicrobials are above minimal inhibitory concentrations (MIC) or antimicrobial European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | Per antimicrobial of interest, we will determine the % of time that free concentrations are above minimal inhibitory concentrations (MIC) or antimicrobial EUCAST breakpoints |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration versus time curve (AUC) | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | Per antimicrobial of interest, we will determine the pharmacokinetic parameter the area under the plasma concentration versus time curve (AUC). |
| Clearance (Cl) | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | Per antimicrobial of interest, we will determine the pharmacokinetic parameter clearance (Cl). |
| Volume of distribution (Vd) | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | Per antimicrobial of interest, we will determine the pharmacokinetic parameter the volume of distribution (Vd). |
| Half life (T1/2) | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | Per antimicrobial of interest, we will determine the pharmacokinetic parameter the half life (T1/2). |
| Risk factors for target non attainment | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | Multivariate analysis will be performed with target attainment as outcome. This will allow to identify risk factors for target non attainment. |
Countries
Belgium
Contacts
Primary ContactPeter Declercq, PharmD
Backup ContactIsabel Spriet, PhD
Outcome results
None listed