Assessment of Appropriateness of an Initial Dosing Regimen of Vancomycin and Development of a New Dosing Nomogram

Abstract

Vancomycin is a glycopeptide antibiotic used to treat Gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The objectives of this study were to evaluate the appropriateness of the initial dosing regimen of vancomycin, identify factors to be considered in regimen selection and develop a new dosing nomogram. Therapeutic drug monitoring (TDM) data of vancomycin obtained from Seoul National University Hospital from 2011 to 2013 were included in this analysis. The vancomycin trough concentrations at steady-state were estimated using Abbott's PKS software program and then categorized into three levels: subtherapeutic, therapeutic and toxic. The newly developed nomograms were evaluated by analysing the percentage of patients with target vancomycin trough concentration using the data of 2,570 patients of the first TDM cases. Therapeutic level was achieved only in approximately one-fifth of the cases, while 56.0% and 23.8% of the TDMs were considered subtherapeutic and toxic, respectively. As body-weight and creatinine clearance (CrCL) increased, the proportion of patients with a subtherapeutic level increased. Using the newly developed nomogram increased the proportion of patients who achieved therapeutic levels from 23.1% to 45.0% or 13.8% to 36.2% (target, 10-15 and 15-20 mg/L, respectively). These results suggest that the vancomycin concentrations fail to reach the therapeutic level or exceed the safe upper margin of the therapeutic level depending on age, body-weight and CrCL. Considering these factors, the new nomograms provide a strategy to achieve target concentrations of vancomycin more rapidly than existing regimens.

Study on the Structure-Activity Relationship of an Antimicrobial Peptide, Brevinin-2GUb, from the Skin Secretion of Hylarana guentheri

“…The higher TI value represents a higher specificity to the microbes, which means it is safer [ 9 ]. For example, the TI of diazepam, which is viewed as a relatively safe drug, is 100:1 [ 39 ], while some antibiotics only have a narrow therapeutic window, such as gentamicin and vancomycin [ 40 ]. However, the TI of tB2U-6K is 158.02, which is the highest among these peptides.…”

Genetic Algorithms as a Tool for Dosing Guideline Optimization: Application to Intermittent Infusion Dosing for Vancomycin in Adults

“…National consensus guidelines that recommended troughs of 15–20 mg/L for patients with serious infections 16–18 has resulted in many new guidelines and nomograms to support vancomycin dosing 19–24 . The methodologies used to create these guidelines ranged from local experience, 21,24–26 regression analysis, 19,23,27,28 simulations based on traditional or population PK models 20,22 to more sophisticated approaches using Monte Carlo simulation 29,30 . In most cases, the numbers of patients used to develop and validate these guidelines was relatively small and the methodology used to choose the dose amounts and intervals unclear.…”

“…In most cases, the numbers of patients used to develop and validate these guidelines was relatively small and the methodology used to choose the dose amounts and intervals unclear. Furthermore, although these guidelines typically improved target achievement when compared with previous approaches, they often focused on specific patient groups or excluded patients outside restricted ranges of weight or renal function 19 …”

Development of a mobile application for vancomycin dosing calculation: A useful tool for the rational use of antimicrobials

“…Therefore, individualization of drug dosage regimens must be performed based on clinical characteristics of each patient, such as weight and estimated creatinine clearance. 3 …”