Researchers recommend that a patient-tailored dosing regimen is used routinely in neonates for continuous infusion therapy of the antibiotic, vancomycin.
Evelyne Jacqz-Aigrain (Hôpital Robert Debré, Paris, France) and team compared three dosing regimens of continuous vancomycin therapy and found that using a loading dose led to fewer neonates with low concentrations of vancomycin. Moreover, target concentrations of the antibiotic were obtained faster than when using intermittent infusion.
Concentrations of vancomycin delivered by continuous infusion in 116 neonates ranged from 5.1 mg/L to 61.5 mg/L.
Only 48 (41.4%) neonates were within the therapeutic range of 15−25 mg/L, 35 had a low (<15 mg/L) or very low (<10 mg/L) serum vancomycin concentration, and 33 had a high serum vancomycin concentration (>20 mg/L).
Low concentrations were observed with dosing regimen 3 (DR3), in which a loading dose was not used, while high concentrations were observed with DR2 using a uniform weight-based dosing regimen with a loading dose of 10−15 mg/kg.
DR1 consisted of a maintenance dose of 20 mg/kg per day at 24−27 weeks' gestation, which rose to 35 mg/kg per day by 32 weeks. DR2 and DR3 both consisted of a maintenance dose of 30 mg/kg per day.
The team then developed an optimized vancomycin dosing regimen taking into account birthweight, current weight, postnatal age, and serum creatinine based on a one-compartment pharmacokinetic model.
A prospective validation study in 58 neonates revealed a higher percentage of neonates reached the therapeutic range and early dosage adaptation (6-12 hours post-dose) using an optimized dosing regimen than those who were on the existing dosing regimen.
After receiving personalized doses, 41 (70.7%) of the neonates in the clinical validation study had reached vancomycin concentrations within the desired therapeutic range of 15−25 mg/L. After dosing adjustment, all neonates achieved the desired therapeutic range, except for three neonates who were not treated with the protocol.
The authors explain that as their study was primarily a pharmacokinetic one, they did not collect efficacy and safety data on vancomycin continuous infusion. They therefore recommend that the next step may be to conduct a randomized controlled trial to compare continuous and intermittent administration of vancomycin.
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