Pharmacokinetics, Amoxicillin-clavulanate, Piperacillin-tazobactam, Meropenem, Cefazolin, Teicoplanin, Vancomycin, Ciprofloxacin, Amikacin
Conditions
Brief summary
Pharmacokinetics of antibiotics in critically ill neonates, infants and children on extracorporeal membrane oxygenation (ECMO).
Detailed description
The study will investigate whether - with the current dosing regimens of meropenem, piperacillin-tazobactam, amoxicillin-clavulanate, cephazolin, vancomycin, amikacin, teicoplanin and ciprofloxacin - pharmacodynamic targets are attained in a national multicentric clinical setting in pediatric patients on ECMO.
Interventions
blood sampling in patients receiving amoxicillin-clavulanate as part of routine clinical care
blood sampling in patients receiving piperacillin-tazobactam as part of routine clinical care.
OTHERMeropenem
blood sampling in patients receiving meropenem as part of routine clinical care.
OTHERCefazolin
blood sampling in patients receiving cefazolin as part of routine clinical care.
OTHERVancomycin
blood sampling in patients receiving vancomycin as part of routine clinical care.
OTHERTeicoplanin
blood sampling in patients receiving teicoplanin as part of routine clinical care.
OTHERCiprofloxacin
blood sampling and urine sampling in patients receiving ciprofloxacin as part of routine clinical care.
OTHERAmikacin
blood sampling in patients receiving amikacin as part of routine clinical care.
Sponsors
University Hospital, Ghent
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 15 Years
Healthy volunteers
No
Inclusion criteria
* patients admitted to the pediatric intensive care unit or cardiac intensive care unit * patient age : 1,8 kg-15 years * patient receiving antibiotic treatment (piperacillin-tazobactam, meropenem, amoxicillin-clavulanate, cephazolin, vancomycin, teicoplanin, ciprofloxacin, amikacin) * intra-arterial or intravenous access other than the drug infusion line available for blood sampling (arterial line is preferred) * extracorporeal membrane oxygenation circuit
Exclusion criteria
* no catheter in place for blood sampling * absence of parental/patient consent * known hypersensitivity to beta-lactam antibiotics and ciprofloxacin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amoxicillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism | up to 1 month | % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions |
| Cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism | up to 1 month | % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions |
| Meropenem: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism | up to 1 month | % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions |
| Piperacillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism | up to 1 month | % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions |
| Amoxicillin, piperacillin, meropenem, cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism | up to 1 month | % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions |
| Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC) | up to 1 month | % of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen off extracorporeal membrane oxygenation in steady-state conditions |
| Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC) | up to 1 month | % of patients in whom a AUC/MIC target 400-600 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions |
| Teicoplanin: probability of target attainment with the target being a mimimal trough concentration | up to 1 month | % of patients in whom a trough concentration between 20 to 30 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions |
| for teicoplanin: probability of target attainment with the target being an Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration Ratio (AUC/MIC) | up to 1 month | % of patients in whom an AUC/MIC of 900 is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions |
| for amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC) | up to 1 month | % of patients in whom a target peak/MIC ratio of 8 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions |
| Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration | up to 1 month | % of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions |
| Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC) | July 2026 | % of patients in whom a target fAUC/MIC ratio of 399 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Risk factors for underdosing during extracorporeal membrane oxygenation for beta-lactam antibiotics | up to 1 month | The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a percentage of time during which the unbound concentration remains above the Minimal Inhibitory Concentration (MIC) of the micro-organism of at least 50% and a maximum concentration of 10 x MIC |
| Risk factors for underdosing during extracorporeal membrane oxygenation for ciprofloxacin | up to 1 month | The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of ciprofloxacin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a free Area-under the concentration-Time Curve of 86 |
| Risk factors for under-and overdosing during extracorporeal membrane oxygenation for vancomycin | up to 1 month | The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of vancomycin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a free Area-under the concentration-Time Curve of 200 to 300 |
| Risk factors for underdosing during extracorporeal membrane oxygenation for teicoplanin | up to 1 month | The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of teicoplanin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is an Area-under the concentration-Time Curve of 900 |
| Risk factors for under-and overdosing during extracorporeal membrane oxygenation for amikacin | up to 1 month | The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of amikacin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a peak over Minimal Inhibitory Concentration Ratio of 8 to 10, trough concentration below 5 mg/L and Area under the Concentration Time Curve/MIC\>399 |
| Beta-lactam antibiotics (amoxicillin, piperacillin, meropenem, cefazolin): probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) | up to 1 month | % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in first dose conditions |
| Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC) | up to 1 month | % of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions |
| Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC) | up to 1 month | % of patients in whom a AUC/MIC target 400-600 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions |
| Teicoplanin: probability of target attainment with the target being a mimimal trough concentration | up to 1 month | % of patients in whom a trough concentration between 20 to 30 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions |
| Amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC) | up to 1 month | % of patients in whom a target peak/MIC ratio of 8 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions |
| Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration | up to 1 month | % of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions |
Countries
Belgium
Contacts
CONTACTPieter De Cock, PharmD
PRINCIPAL_INVESTIGATORAnnick de Jaeger, MD
University Hospital, Ghent
Outcome results
None listed