Target Attainment and Pharmacokinetics of Antimicrobials in Non-critically Ill Surgery Patients (TAPAS)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Target Attainment and Pharmacokinetics of Antimicrobials in Non-critically Ill Surgery Patients

Conditions
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Surgery

Intervention / Treatment
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* Drug: amoxicillin-clavulanic acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: amoxicillin-clavulanic acid|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 .|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The % of time that free concentrations of antimicrobials are above minimal inhibitory concentrations (MIC) or antimicrobial European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints | Per antimicrobial of interest, we will determine the % of time that free concentrations are above minimal inhibitory concentrations (MIC) or antimicrobial EUCAST breakpoints | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | Per antimicrobial of interest, we will determine the pharmacokinetic parameter the 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. | 
| Clearance (Cl) | Per antimicrobial of interest, we will determine the pharmacokinetic parameter clearance (Cl). | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | 
| Volume of distribution (Vd) | Per antimicrobial of interest, we will determine the pharmacokinetic parameter the volume of distribution (Vd). | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | 
| Half life (T1/2) | Per antimicrobial of interest, we will determine the pharmacokinetic parameter the half life (T1/2). | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | 
| Risk factors for target non attainment | Multivariate analysis will be performed with target attainment as outcome. This will allow to identify risk factors for target non attainment. | During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antimicrobials, pharmacokinetics, augmented renal clearance, non critically ill