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

• Conditions: Surgery

• Registration Number: NCT03120663
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

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.

Study Timeline

• Study Start: 2016-11-30
• Status Verified: 2017-04
• Study First Submitted: 2017-04-04
• Study First Submitted QC: 2017-04-14
• Study First Posted: 2017-04-19
• Last Update Submitted: 2017-04-19
• Last Update Posted: 2017-04-20
• Primary Completion: 2018-09-30
• Study Completion: 2018-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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).
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.
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).

Trial Locations

Locations (1)

University Hospitals Leuven; 🇧🇪 Leuven, Belgium