Vancomycin dosing in children: what is the question?

Abstract

Vancomycin has been in clinical use for over 60 years, but it is still not clear what dose should be given to children. Effective treatment with vancomycin requires a serum concentration well above the minimum inhibitory concentration (MIC) of the bacteria being treated. This is predicted by the area under the concentration curve (AUC) divided by the MIC being >400 (AUC/MIC). Recent concerns about increasing MIC in staphylococci have lead to recommendations to aim for higher trough vancomycin levels (15-20 mg/L). In current practice, most children do not achieve these trough levels. Modelling and pharmacokinetic studies in children suggest these trough levels may not be necessary if the MIC of the organisms is 1 mg/L or less. Further, large-scale studies are needed to determine the most appropriate dosing of vancomycin in children. While awaiting these, it is time to consider moving to 15 mg/kg 6 h as a standard starting regime for vancomycin. It is also vital to determine the MIC of the organism being treated, as this may give some guidance about suitable trough levels to be aimed for. There is currently little evidence to guide the use of loading doses or continuous vancomycin infusions in children.

Balancing Vancomycin Efficacy and Nephrotoxicity: Should We Be Aiming for Trough or AUC/MIC?

“…There are concerns that patients with a vancomycin MIC C2 lg/mL are more likely to result in treatment failure, along with a greater risk of morbidity and mortality [19]. With trough concentrations \10 lg/mL and the continued use of vancomycin at higher MICs, there is also a possible risk for the emergence of inducible, heterogeneous vancomycin-intermediate S. aureus (hVISA) strains [2,20]. Clinicians are now beginning to consider alternate agents as per guideline recommendations, rather than target higher vancomycin trough concentrations of 15-20 lg/mL when MICs are C2 lg/mL.…”

Evaluation of Vancomycin Dosing and Corresponding Drug Concentrations in Pediatric Patients

“…15 In our study we attempted to investigate this relationship and explore the potential infl uence of age on trough concentrations. Because our review spans the time frame before and after publication of the IDSA dosing guidelines recommending the higher vancomycin dosing strategy, we were also interested to see whether prescribing patterns had changed without an official protocol.…”

Paediatric pharmacokinetics and drug doses

“…Even for vancomycin, for which therapeutic drug monitoring is commonly performed, this information is not available. 15 More information is available regarding the safe and effective concentrations of antiepileptic drugs in children, although therapeutic drug monitoring cannot predict all adverse effects, such as hepatotoxicity with sodium valproate.…”