Kidney Failure, Chronic, Antibiotics, Hemodialysis
Conditions
Brief summary
The adequacy of the currently used dosing regimen of glycopeptides (vancomycin and teicoplanin) and beta-lactam antibiotics (amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidim) in patients with end-stage kidney disease receiving intermittent hemodialysis is studied by evaluating pharmacokinetics-pharmacodynamics (PK-PD) target attainment. A population pharmacokinetic study is performed to assist the selection of the optimal individualized dose for patients undergoing intermittent dialysis, taking into consideration as many relevant variables as possible.
Interventions
During a period of maximum 6 days blood is sampled at different time points and urine is collected during documented time intervals.
Sponsors
University Ghent
University Hospital, Ghent
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients with end-stage kidney disease, requiring intermittent hemodialysis * patient receiving antibiotic treatment for documented or presumed infection (vancomycin, teicoplanin, amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidim)
Exclusion criteria
* pregnant woman * absence of written informed consent from the patient * known hypersensitivity or contra-indication to glycopeptides or beta-lactam antibiotics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of ceftazidim in patients undergoing intermittent hemodialysis | 9/2016 - 12/2021 | Population pharmacokinetic modeling is performed based on the measured ceftazidim concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured ceftazidim concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance. |
| Blood concentrations with maximal antimicrobial activity versus current dosing regimens for ceftazidim | 9/2016 - 12/2021 | Measured concentration of the beta-lactam ceftazidim is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%. |
| Pharmacokinetics of vancomycin in patients undergoing intermittent hemodialysis | 9/2016 - 12/2021 | Population pharmacokinetic modeling is performed based on the measured vancomycin concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured vancomycin concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance. |
| Pharmacokinetics of teicoplanin in patients undergoing intermittent hemodialysis | 9/2016 - 12/2021 | Population pharmacokinetic modeling is performed based on the measured teicoplanin concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured teicoplanin concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance. |
| Pharmacokinetics of amoxicillin-clavulanic acid in patients undergoing intermittent hemodialysis | 9/2016 - 12/2021 | Population pharmacokinetic modeling is performed based on the measured amoxicillin-clavulanic acid concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured amoxicillin-clavulanic acid concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance. |
| Pharmacokinetics of piperacillin-tazobactam in patients undergoing intermittent hemodialysis | 9/2016 - 12/2021 | Population pharmacokinetic modeling is performed based on the measured piperacillin-tazobactam concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured piperacillin-tazobactam concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance. |
| Blood concentrations with maximal antimicrobial activity versus current dosing regimens for vancomycin | 9/2016 - 12/2021 | Measured free and total concentration of the glycopeptide vancomycin is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: Area Under the Curve (AUC) from 0-24h in steady-state divided by the Minimum Inhibitory Concentration (MIC) of the suspected pathogen should be \>=400 for vancomycin. |
| Blood concentrations with maximal antimicrobial activity versus current dosing regimens for teicoplanin | 9/2016 - 12/2021 | Measured free and total concentration of the glycopeptide teicoplanin is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: Area Under the Curve (AUC) from 0-24h in steady-state divided by the Minimum Inhibitory Concentration (MIC) of the suspected pathogen should be \>=750 for teicoplanin. |
| Blood concentrations with maximal antimicrobial activity versus current dosing regimens for amoxicillin-clavulanic acid | 9/2016 - 12/2021 | Measured concentration of the beta-lactam amoxicillin-clavulanic acid is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%. |
| Blood concentrations with maximal antimicrobial activity versus current dosing regimens for piperacillin-tazobactam | 9/2016 - 12/2021 | Measured concentration of the beta-lactam piperacillin-tazobactam is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dialyser extraction rate of teicoplanin | 9/2016 - 12/2021 | From dialyser inlet and outlet samples, the extraction ratio is calculated for teicoplanin and entered in the kinetic analysis |
| Dialyser extraction rate of amoxicillin-clavulanic acid | 9/2016 - 12/2021 | From dialyser inlet and outlet samples, the extraction ratio is calculated for amoxicillin-clavulanic acid and entered in the kinetic analysis |
| Dialyser extraction rate of piperacillin-tazobactam | 9/2016 - 12/2021 | From dialyser inlet and outlet samples, the extraction ratio is calculated for piperacillin-tazobactam and entered in the kinetic analysis |
| Dialyser extraction rate of ceftazidim | 9/2016 - 12/2021 | From dialyser inlet and outlet samples, the extraction ratio is calculated for ceftazidim and entered in the kinetic analysis |
| Dialyser extraction rate of vancomycin | 9/2016 - 12/2021 | From dialyser inlet and outlet samples, the extraction ratio is calculated for vancomycin and entered in the kinetic analysis |
Countries
Belgium
Outcome results
None listed