A challenge to intermittent vancomycin dosing in young infants is the avoidable delay caused by the need to wait until steady state (i.e. when the drug concentrations are in equilibrium) to measure a vancomycin concentration, as this generally occurs 24 to 48 hours after starting treatment. If the target concentration is not achieved, the dose needs to be adjusted, resulting in further delays in an infant achieving the concentration required to treat their infection. The purpose of this study is to assess the use of early therapeutic drug monitoring (first-dose trough) and, if needed, early dose adjustment, in achieving target vancomycin concentrations at steady state. A dose adjustment calculator (available through a web application) will be used to determine the need for dose adjustment (based on predicted steady state concentration) and recommend an adjusted dose if required.
Infants aged 0 - 90 days old
Suspected infection requiring treatment with vancomycin for 48 hours or more (as determined by the clinical team)
Infants with a corrected gestational age of less than 25 weeks
Infants weighing less than 500g.
Known allergy to any glycopeptide antibiotic
Vancomycin administered within the previous 72 hours
Single group
First-dose trough dose adjustment calculator - using early TDM (first-dose trough) to determine an early dose adjustment if the predicted steady-state trough is outside of target range (10-20mg/L)
Other interventionCALCULATOR: A 'First-dose trough dose adjustment calculator' was developed based on a population pharmacokinetic model. A participant's post-menstrual age, weight, creatinine, target trough concentration, dose, dosing interval and first-dose trough concentration (taken immediately before the second dose is due) are entered into the calculator. The calculator determines if a dose adjustment is required (based on whether the predicted steady-state trough concentration is \<10mg/L or \>20mg/L) and, if required, recommends a new adjusted dose.
Target concentration at first steady-state concentration
The proportion of young infants achieving target trough serum vancomycin concentrations (10 to 20 mg/L) at first steady-state level when model-based dosing is used followed by early therapeutic drug monitoring (and dose adjustment) after the first dose
Sub- and supratherapeutic concentrations at first steady-state concentration
The proportion of young infants with supra- (defined as \>20mg/L) or sub- (defined as \<10mg/L) therapeutic vancomycin concentrations at the first steady state level when model-based dosing is used followed by early therapeutic drug monitoring (and dose adjustment) after the first dose
Drug-related adverse effects
The frequency of drug-related adverse effects (infusion-related and nephrotoxicity).
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Murdoch Childrens Research Institute
Lead sponsor
Royal Children's Hospital
Collaborator
Royal Hospital For Women
Collaborator
Sydney Children's Hospitals Network
Collaborator
Monash Health
Collaborator
