Pharmacokinetics of antibiotics in critically ill neonates, infants and children on extracorporeal membrane oxygenation (ECMO).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
300
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.
blood sampling in patients receiving meropenem as part of routine clinical care.
blood sampling in patients receiving cefazolin as part of routine clinical care.
blood sampling in patients receiving vancomycin as part of routine clinical care.
blood sampling in patients receiving teicoplanin as part of routine clinical care.
blood sampling and urine sampling in patients receiving ciprofloxacin as part of routine clinical care.
blood sampling in patients receiving amikacin as part of routine clinical care.
Queen Fabiola Children's University Hospital
Brussels, Brussels Capital, Belgium
RECRUITINGUniversity Hospital
Ghent, Belgium
RECRUITINGUniversitair hospital
Leuven, Belgium
RECRUITINGAmoxicillin: 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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
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
% 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
Time frame: up to 1 month
Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)
% of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen off extracorporeal membrane oxygenation in steady-state conditions
Time frame: up to 1 month
Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)
% 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
Time frame: up to 1 month
Teicoplanin: probability of target attainment with the target being a mimimal trough concentration
% 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
Time frame: up to 1 month
for teicoplanin: probability of target attainment with the target being an Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration Ratio (AUC/MIC)
% 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
Time frame: up to 1 month
for amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)
% 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
Time frame: up to 1 month
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration
% 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
Time frame: up to 1 month
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration
% of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions
Time frame: up to 1 month
Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)
% 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
Time frame: July 2026
Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)
% of patients in whom a target fAUC/MIC ratio of 399 is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions
Time frame: July 2026
Risk factors for underdosing during extracorporeal membrane oxygenation for beta-lactam antibiotics
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
Time frame: up to 1 month
Risk factors for underdosing during extracorporeal membrane oxygenation for ciprofloxacin
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
Time frame: up to 1 month
Risk factors for under-and overdosing during extracorporeal membrane oxygenation for vancomycin
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
Time frame: up to 1 month
Risk factors for underdosing during extracorporeal membrane oxygenation for teicoplanin
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
Time frame: up to 1 month
Risk factors for under-and overdosing during extracorporeal membrane oxygenation for amikacin
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
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Time frame: up to 1 month
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)
% 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
Time frame: up to 1 month
Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)
% of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions
Time frame: up to 1 month
Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)
% 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
Time frame: up to 1 month
Teicoplanin: probability of target attainment with the target being a mimimal trough concentration
% 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
Time frame: up to 1 month
Amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)
% 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
Time frame: up to 1 month
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration
% 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
Time frame: up to 1 month