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The Complete Guide to Vancomycin Dosing in 2020 for Hospital Pharmacists
New vancomycin dosing and therapeutic monitoring guidelines were published in March 2020, marking the first major update to vancomycin dosing standards since 2009, when the first set of consensus guidelines were published.
The recommendations within the new guidelines mark notable shifts in the way clinical pharmacists, ID pharmacists, directors of pharmacy, and other members of the healthcare team should be thinking about and planning for vancomycin dosing and therapeutic drug monitoring.
However, findings from a recent survey of 126 hospital directors of pharmacy and pharmacists showed that 86% of respondents are still using dosing methods that the new guidelines indicate should be discontinued.
We created this comprehensive vancomycin dosing guide to provide you with the information you need to align your institution’s vancomycin dosing practices to the newly released consensus guidelines.
A Brief Review of Basic Vancomycin Pharmacokinetics
This review of vancomycin pharmacokinetics (PK) will help make sure you’re primed to understand the shifts in the new guidelines:
- Peak - The highest serum concentration of vancomycin in the body, with a traditional reference range of 20-40 mg/L at steady state
- Trough - The lowest serum concentration of vancomycin in the body, with a traditional reference range of 15-20 mg/L for serious methicillin-resistant Staphylococcus aureus (MRSA) infections
- Area Under the Curve (AUC) - The area under the curve that relates serum concentration of vancomycin to time
- Minimum Inhibitory Concentration (MIC) - The lowest concentration of vancomycin that will prevent bacterial growth, which is usually assumed at 1 mg/L, often determined by broth microdilution (BMD)
- AUC24/MIC ratio - The 24-hour AUC to MIC ratio, which is most accurate measurement of vancomycin activity
Methods of Vancomycin Dosing and Monitoring
Now, we’ll explore the recommendations for dosing and monitoring vancomycin, according to traditional and newly recommended methods.
Vancomycin Trough Levels—Traditional Method
The original 2009 vancomycin dosing guidelines:
- Ended routine serum peak concentration monitoring
- Established the main measure of vancomycin activity and efficacy as AUC24/MIC >= 400
- Recommended using serum trough levels of 15-20 mg/L as surrogate markers of the AUC24/MIC measure
It’s important to realize that the 2009 recommendation to dose vancomycin based on serum trough levels was one of convenience and practicality. Trough levels merely served as surrogate markers for AUC since historically, AUC had been so difficult to estimate.
But in reality, vancomycin trough levels are not ideal surrogate markers. Trough levels do not correlate well with AUC values. In other words, different vancomycin doses based on a variety of disparate AUC values can actually result in very similar trough levels.
This makes sense if you consider that a trough level gives you a snapshot of one specific moment—the end of the dosing interval—whereas the AUC gives you an idea of the average vancomycin concentration over a 24-hour period.
Given its improved accuracy, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Disease Pharmacists have shifted to recommending an AUC-based dosing approach, rather than a trough-based approach.
Using AUC to Optimize Vancomycin Dosing—Newly Recommended Method
Over the past decade there have been several published studies concluding that AUC vancomycin dosing is a more accurate way to maximize the antibiotic’s efficacy while minimizing the risk of nephrotoxicity, which impacts a quarter or more of vancomycin patients.
As a result, the consensus guideline team came to this conclusion: “To optimize vancomycin use for the treatment of serious infections caused by MRSA, we recommend targeting an AUC/MICBMD ratio of 400-600 for empiric dosing in both adult and pediatric patients to maximize the clinical efficacy and minimize AKI…”
But one major hold-up for pharmacy and hospital teams is figuring out exactly how to switch to AUC-based dosing. The consensus guidelines offer two possible solutions, with the first being preferred.
We’ll investigate each option, as well as its pros and cons.
Vancomycin AUC Dosing: Bayesian method
What is Bayesian Dosing?
Bayesian-guided dosing is based on Bayesian principles and modeling. Bayesian dosing combines known trends in population PK with an individual patient’s data and laboratory results to accurately and precisely simulate patient-specific AUC exposure for a given dose.
Put simply, it combines existing, known populational data with new, patient-specific data to enable clinicians to determine a vancomycin dosing regimen likely to get that specific patient into the ideal AUC range. Because the software is continuously acquiring new patient-specific data, the AUC predictions become more accurate over a patient’s treatment course.
What are the Advantages of Bayesian Dosing?
Clinical teams can only realistically employ Bayesian dosing with the help of Bayesian dosing software. Using this software, no manual calculations are necessary.
Bayesian dosing also offers more flexibility, allowing for use of a 1-level (trough only, or even a “random” level) or 2-level (trough and peak) sampling approach. However, using 2 levels increases the accuracy of the software and is more appropriate in certain populations such as obese, critically ill, and pediatric patients.
The Bayesian method allows for sample collection and potential dose adjustment during the first 24 to 48 hours of a vancomycin regimen. This is in contrast to the trough-based dosing approach, which confines you to sample collection only after steady state is reached.
Vancomycin AUC Dosing: Manual calculations
If you choose to use calculations to estimate AUC, you’ll either perform manual calculations using PK equations, or you’ll use calculators or nomograms based on various PK equations.
In addition to being laborious, the manual calculation method requires two blood draws: a trough and a peak. And as you know, the timing of these blood draws is quite particular.
The peak serum level should ideally be taken at steady state, one to two hours after the vancomycin infusion ends. The trough level is ideally taken within that same dosing interval. If not taken at the optimal times, the samples may be unusable, or risk inaccurate predictions.
Here are two examples of equation-based methods of estimating AUC:
1. Rodvold method - The Rodvold calculation uses first-order PK equations to estimate the AUC based on two steady-state samples. It’s a relatively quick equation to perform—one that you may already be familiar with.
Its major drawback is that it underestimates the true AUC. The likelihood of an inaccurate AUC estimate is even greater if a patient is receiving more than one dose of vancomycin per 24 hours.
Unlike the Bayesian method, the Rodvold calculation does not become more accurate over a patient’s treatment course. Rather, it gives a snapshot of the AUC for that particular sampling period without taking patient-specific physiological changes into account. For example, if a patient’s renal function declines, the AUC estimate will no longer be accurate, which puts the patient at a higher risk of AKI.
2. Trapezoidal method - This calculation is based on the linear-trapezoid rule, where multiple vancomycin concentrations would need to be taken from within the same dosing interval. While it allows for more individualized dosing than the Rodvold calculation, it takes much more time and isn’t as practical.
Vancomycin calculators and nomograms
Online vancomycin calculators and nomograms you may use in your hospital are based on a variety of PK equations, depending on the specific calculator or nomogram. While some of these resources may offer a solid starting point for dosing vancomycin patients, they are not capable of estimating AUC as individually and precisely as Bayesian modeling.
Choosing a Vancomycin Dosing Method
There are several factors you’ll want to consider when it comes to choosing the best vancomycin dosing method for your hospital or health system:
- AUC estimation & prediction accuracy - Your chosen method should allow you to estimate the AUC as accurately as possible so that you can be certain you’re maximizing clinical efficacy and minimizing the risk of adverse events for your patients. In terms of precision and accuracy, the Bayesian method is the clear winner.
Winner: Bayesian method
- Vancomycin concentration sampling and timing - If flexibility and workflow simplification are important to you, you’ll want to select a method that allows you to choose between a 1-level or 2-level approach and is not as restrictive from a timing standpoint. Manual calculations require 2 samples, whereas the Bayesian method can be performed using only a trough level—and even a “random” level can still produce accurate AUC estimates.
Winner: Bayesian method
- Pharmacist time - Pharmacist efficiency is directly impacted by the pharmacy department’s AUC estimation standards and protocols. Manual calculations, calculators, and nomograms can be slow and tedious, requiring significant mental energy and leaving room for human error. Conversely, Bayesian software—when integrated with your institution’s electronic health record (EHR) system—allows for much faster AUC estimation that is more precise with less room for error.
Winner: Bayesian method (if EHR-integrated)
- Financial Costs - Of course, you’ll need to consider your pharmacy’s budget and whether there are funds for Bayesian software. Financial costs will differ, depending on the specific third-party vendor.
Winner: Manual calculations
- Indirect Costs - Monetary costs are not the only costs you should consider. Don’t forget to factor in the cost of nephrotoxicity and AKI, wasted samples, and pharmacist time spent on time-consuming processes. After evaluating financial and time costs, you might find that it is more affordable to invest in Bayesian software.
Winner: Bayesian method
Getting Started with Precision Dosing Software
If you’ve made it this far, you might be wondering how to go about finding these Bayesian dosing software programs the new consensus guidelines recommend. Also known as precision dosing software, these programs have several benefits, including:
- Optimizing patient-specific vancomycin doses
- Maximizing clinical efficacy
- Minimizing risk of nephrotoxicity, such as AKI
- Increasing efficiency of clinical pharmacy teams and ID pharmacists
- Reducing logistical sampling burden of nursing and phlebotomy teams
Potential cost-savings is also apparent when you consider the time saved and the reduction in negative patient health outcomes. In order to realize these cost savings, you’ll of course need to balance the benefits of precision dosing software with the financial costs of the software itself.
Our company, InsightRX, prides itself on offering precision dosing software built by pharmacists, for pharmacists. We use only the most rigorous, high-quality research to inform our Bayesian models and commit to continuously updating and improving our models—as well as developing new ones—so that our hospital and health system partners have constant access to the latest, greatest models.
For a digestible summary of the 2020 vancomycin dosing guidelines to share with your clinical pharmacist colleagues and Director of Pharmacy, read our new vancomycin dosing guidelines white paper.