Paediatric vancomycin dosing
KEY POINTS TO REMEMBER: All patients should receive loading doses. Trough concentrations should be done prior to the 2nd maintenance dose. All patients should have a baseline creatinine, or a creatinine taken with the trough concentration prior to the 2nd maintenance dose. Do not dose-adjust vancomycin according to trough concentrations. Clinical Pharmacology should be contacted when vancomycin i
KEY POINTS TO REMEMBER:
- All patients should receive loading doses.
- Trough concentrations should be done prior to the 2nd maintenance dose.
- All patients should have a baseline creatinine, or a creatinine taken with the trough concentration prior to the 2nd maintenance dose.
- Do not dose-adjust vancomycin according to trough concentrations.
- Clinical Pharmacology should be contacted when vancomycin is commenced for assistance with AUC calculations.
Vancomycin, a glycopeptide antimicrobial, inhibits cell wall synthesis by binding to cell wall precursors and inhibiting glycopeptide polymerization.[1] Vancomycin is effective against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, penicillin-resistant streptococci and ampicillin-resistant enterococci.[1]
What are the indications and antibiotic policy for prescribing vancomycin?
Vancomycin should be used for suspected or confirmed methicillin-resistant Staphylococcus aureus. It is important to remember that vancomycin is less effective than beta-lactams against Staphylococcus aureus that is susceptible to cloxacillin/methicillin. All vancomycin prescriptions should be discussed with, and authorized (written signature or telephonic with pharmacy) by the managing consultant. In addition, they should be discussed on weekly stewardship rounds.
Table 1: Vancomycin intermitted dosing in the paediatric population[2–5]
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Click on image to enlarge
How should vancomycin be dosed?
The pharmacokinetic/pharmacodynamic (PK/PD) parameter of efficacy for vancomycin is the area under the concentration-time curve over the minimum inhibitory concentration (AUC/MIC). A loading dose is recommended to achieve optimal AUC/MIC early in the treatment course. This is particularly important for patients who may have a significantly increased volume of distribution and in the setting of severe sepsis and septic shock.
How should vancomycin be administered?
Vancomycin should be diluted to 500 mg/100 mL and given intravenously as a slow infusion over 60 minutes. The infusion should not run at a rate of more than 500 mg per 30 minutes.
How should vancomycin be monitored?
Vancomycin has a narrow therapeutic index. Adequate concentrations are essential for effective clinical response and reduced toxicity. Inappropriate dosing is associated with treatment failure, resistance and toxicity. Traditionally, trough concentrations were used to monitor vancomycin because it is convenient and pragmatic.[5] A trough concentration is the lowest concentration in the dosing interval. However, this is not the best measure to assess exposures of vancomycin.[6,7] An AUC of 400-600 is associated with better outcomes provided that the MIC of the suspected organism is 1 mg/L.[5] This is also a safer way to monitor the exposure and prevent complications.
An AUC can be calculated and used to individualize the vancomycin dose using software that utilizes Bayesian analysis. The Division of Clinical Pharmacology has a license to access this software and can use the trough concentrations to assess the appropriateness of the dose and to predict dosing for individual patients. Trough concentrations should be performed just prior to the 3rd dose and weekly for children in longer term therapy with stable renal function. Vancomycin is eliminated almost exclusively via the kidneys,[1] and therefore a change in renal function could affect vancomycin exposures. Conversely, toxic vancomycin concentrations can cause renal dysfunction and care should be taken when vancomycin is administered with other nephrotoxic drugs.
The Clinical Pharmacologist on call must be consulted when administering vancomycin in a patient with impaired renal function for renally adjusted doses, for AUC/MIC ratio calculations, or for any other vancomycin related queries.
References
- Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th editi. McGraw-Hill Education; 2018.
- Jacqz-Aigrain E, Leroux S, Thomson AH, et al. Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants. J Antimicrob Chemother 2019;74(8):2128–2138. https://doi.org/10.1093/jac/dkz158
- Janssen EJH, Välitalo PAJ, Allegaert K, et al. Towards rational dosing algorithms for vancomycin in neonates and infants based on population pharmacokinetic modeling. Antimicrob Agents Chemother 2016;60(2):1013–1021. https://doi. org/10.1128/AAC.01968-15
- Cristina G, Alves S, Dutra Da Silva S, et al. Determining the optimal vancomycin daily dose for pediatrics: a meta-analysis. https://doi.org/10.1007/s00228-017- 2306-3
- Rybak MJ, Le J, Lodise TP, et al. Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of HealthSystem Pharmacists, the Infectious Diseases Society of A. Pharmacotherapy 2020;40(4):363–367. https://doi.org/10.1002/phar.2376
- Chen Y, Wu D, Dong M, et al. Population pharmacokinetics of vancomycin and AUC-guided dosing in Chinese neonates and young infants. Eur J Clin Pharmacol 2018;74(7):921–930. https://doi.org/10.1007/s00228-018-2454-0
- Lewis P. Vancomycin Area Under the Curve Simplified. 2018.
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