Vancomycin, an antibiotic medication used to treat serious bacterial infections, can lead to increased nephrotoxicity without improved efficacy if administered in an excessive dosage, or can fail to achieve the desired therapeutic effect if underdosed.
During a June 2022 Becker's Hospital Review webinar sponsored by InsightRX — a precision medicine software company that empowers life science and provider healthcare organizations to individualize treatment from clinical development to the point of care — Jon Faldasz, PharmD, Senior Director of Product and Customer Experience at InsightRX, and Craig Randall, Antimicrobial Stewardship Manager at Wentworth-Douglass Hospital (Dover, N.H.), discussed how Area Under the Curve (AUC)-guided dosing using a Bayesian software program can improve AUC target attainment for vancomycin.
Three key takeaways were:
- The optimal way to manage vancomycin dosing is through AUC-guided dosing. Per consensus guidelines published in 2020, targeting AUC is both optimal and feasible, allowing patient dosing that maximizes efficacy while minimizing toxicity. The guidance also indicated that the preferred approach to measure AUC is through Bayesian software programs.
Bayesian forecasting as applied to drug dosing is a subset of model-informed precision dosing (MIPD). MIPD constitutes the use of a pharmacokinetic (PK) model to aid in more accurate and more precise dosing. Bayesian forecasting applies MIPD in the setting of measured drug concentrations, balancing the expected and observed values to individualize pharmacokinetic predictions beyond the model and further improve the accuracy of precision of predictions.
"When [we] put these things together in a software, we can convert levels to an exposure metric like AUC very easily," Dr. Faldasz said. "We're able to interpret levels from any time point, regardless of dosing history, and the platform calculates the residual exposure available for each dose." InsightRX's precision dosing software, InsightRX Nova, provides multiple PK models specific to different patient populations. - Teams in charge of dosing protocols can compare different AUC and PK calculators. Various tools that facilitate PK calculations exist on the market and clinical pharmacy teams should do their due diligence when evaluating a best fit for their needs. At Wentworth-Douglass, the clinical pharmacy team researched and evaluated the Epic embedded AUC calculator, InsightRX and other paid and free calculators such as DoseMeRx and ClinCalc.com.
"The biggest reason why we chose InsightRX is that you can use a single random level [versus the traditional two, peak and trough, levels]. AUC levels can be assessed within the first 24 hours of therapy, so we're able to achieve therapeutic targets faster and there's increased accuracy in special populations, such as obesity," Dr. Randall said. He added that the cost of subscribing to InsightRX's software was completely offset by eliminating a duplicative referential database. - Wentworth-Douglass conducted a year-long study to assess the effects of the pharmacy-driven AUC policy. The primary outcome of the study was a comparison between the percentage of therapeutic troughs (pre-protocol) and therapeutic AUC (post-protocol) within 48 hours of protocol initiation. One of the underlying motivations for the study was a recognition that the hospital's pharmacy team had a tendency to under-dose vancomycin. So, while they had done a great job preventing toxicity, they saw many patients with subtherapeutic levels.
The experiment revealed that AUC-based dosing for vancomycin increased the accuracy of appropriately drawn levels from 70 percent to 97 percent. It also led to the creation of an electronic historical database of patients to increase accuracy for subsequent treatments.
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