Preparing for the New Vancomycin Guidelines – What Should You Be Considering?

The long-awaited updated guidelines for vancomycin dosing and monitoring are forthcoming. You may be considering how to prepare for this significant change from trough-based monitoring of vancomycin to AUC-based dosing strategies. DoseMe has supported hundreds of customers with the transition and have been able to provide insights into overcoming the challenges this change management process may bring.

Now is the time for pharmacists and healthcare providers to prepare for the guideline changes. Topics to consider include:

The proposed new vancomycin guidelines: what’s changing?
The benefit of Bayesian dosing for vancomycin optimization —features and benefits
What should we be doing now to prepare for AUC-based dosing?

The New Vancomycin Dosing Guidelines: What’s Changing?

These guidelines replace the previous version published a decade ago.¹Intravenous vancomycin is one of the most commonly used antibiotics in healthcare. Although vancomycin has been in use for over 60 years, new information is continually emerging on how to maximize the efficacy of the drug while minimizing toxicity.

While it was once standard to monitor both a peak and a trough serum concentration, in the 2009 guidelines, a peak was no longer recommended. The available evidence at the time of the 2009 guidelines indicated monitoring peaks did not reduce vancomycin-induced nephrotoxicity.

The 2009 vancomycin therapeutic guidelines introduced the concept of dosing based on Area Under the Curve (AUC) and established the relationship between the AUC and the minimum inhibitory concentration (MIC) or AUC:MIC as a “useful pharmacodynamic parameter to predict effectiveness.” However, due to the burden of obtaining multiple serum vancomycin levels along with the challenges of performing AUC mathematical calculations, the guideline authors recommended using a vancomycin trough level for use as a possible surrogate.

Since those 2009 guidelines were published, more research has emerged. Thus healthcare is migrating away from trough-based dosing and towards AUC based dosing.

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This will create a huge paradigm shift in how vancomycin therapy will be monitored moving forward, especially for the treatment of methicillin resistant Staphylococcus aureus (MRSA). The upcoming guidelines, which are currently in draft form² are firmly recommending AUC:MIC as the optimal pharmacodynamic target.

The Benefit of Bayesian Dosing for Vancomycin Optimization

Bayesian dosing uses patient data and laboratory results, when available, in conjunction with a published population model, to recommend an individualized dose of vancomycin for that patient. The proposed vancomycin therapeutic guidelines recommend population pharmacokinetic modelling with the use of Bayesian software – what many are now referring to as the gold standard of clinical decision support for vancomycin dosing and monitoring.

In their discussion of the numerous benefits of Bayesian dosing, often referred to as ‘precision dosing,’ the authors identify a few advantages to the modelling approach, such as:

Reduces reliance on timing of timing of drug levels
Less drug levels required to accurately estimate AUC
Drug levels can be taken before steady state
Bayesian models are dynamic – the individualized PK/PD model is continuously learning over time

What Should We Be Doing Now to Prepare?

It is important to begin discussing these upcoming guideline changes with your teams, including nursing, pharmacy, and the medical staff.

Key topics to address include:

Basic definitions

Many of our partners found it helpful to review the basics of pharmacokinetics and pharmacodynamics with their teams, such as half-life, volume of distribution, and AUC. DoseMe provides a vancomycin pharmacokinetics refresher that is a helpful resource for pharmacy staff and clinicians.

Clinical rationale

The new proposed guidelines recommend a Bayesian-derived AUC/MIC_BMD* ratio of 400 to 600 (assuming a vancomycin MIC_BMD90 of 1 mg/L). Prescribers may not be fully aware of the literature highlighting the therapeutic benefit of shifting away from dosing based on a trough level and towards calculation of an AUC to help guide dosing decisions.

*BMD = Broth microdilution

Education

DoseMe customers have recognized that interdisciplinary education about AUC-guided dosing is needed and is a critical component of a successful transition. Assistant Professor Luigi Brunetti, PharmD, MPH Clinical Pharmacist at Robert Wood Johnson University Hospital Somerset, discusses strategies for incorporating AUC-based dosing approaches into clinical workflow in this CE accredited course: Optimizing Vancomycin Therapy: Transitioning from trough based to AUC/MIC based dosing.

Dr. Brunetti advocates for engaging the appropriate partners in the conversation including not only pharmacy, but also physicians (including infectious diseases), laboratory staff, and nursing. Soliciting input from each group will help to identify the topics that need additional education and will help pharmacy to customize training and education ducation towards for each of these audiences. In addition, it is important to start to have conversations with these groups to understand the upcoming changes to your pharmacy workflow in order to adjust to dosing and monitoring based on AUC.

Improved safety benefit

Multiple clinical studies have shown that AUC-based vancomycin therapy can reduce the occurrence of vancomycin associated acute kidney injury (AKI). Vancomycin-associated AKI is commonly defined as 1) an increase in serum creatinine of ≥ 0.5 mg/dL or 2) a 50% increase from baseline in consecutive daily readings, or 3) a decrease in calculated creatinine clearance of 50% from baseline on two consecutive days in the absence of an alternative explanation. Newer studies suggest that a more sensitive threshold of an increase in serum creatinine ≥ 0.3 mg/dL over a 48-hour period may be an indicator of AKI.

There are multiple publications that provide an excellent review of vancomycin associated AKI. These include:

Making the change to area under the curve-based vancomycin dosing (Heil et al., 2018)
Vancomycin and the risk of AKI: a systematic review and meta-analysis (Sinha Ray et al., 2016)
Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter (van Hal, Paterson and Lodise, 2012)

AUC-based Monitoring of Vancomycin Literature Review

We have compiled a list of independent research related to AUC-based monitoring of vancomycin shown to enhance patient outcomes, reduce adverse drug events, and lower healthcare costs. This research also highlights some of the challenges associated with the implementation of an AUC-based approach and evidence supporting the relationship between AUC:MIC and clinical outcomes – read now.

Next steps: Reviewing Bayesian Dosing

Reviewing Bayesian dosing and understanding how a Bayesian dosing software, such as DoseMeRx, can support your vancomycin monitoring program. There is a preference given in the guidelines towards monitoring AUC using Bayesian software. By using a program that is supported by richly sampled vancomycin data (referred to as Bayesian prior), the pharmacist or other individual responsible for monitoring vancomycin can utilize the Bayesian dosing software to calculate doses designed to achieve the targeted AUC range.
Depending on your hospital’s patient population, another advantage of considering a Bayesian program is that it can accommodate multiple vancomycin models. This can assist you across adult, pediatric and neonate patients, including obese and hemodialysis sub populations.

Levels: decreased reliance of timing and counts

Although obtaining two levels (e.g. a trough and then a peak 1-2 hours after the end of the infusion) is optional, Bayesian dosing allows the use of a single level – thus, no nursing or phlebotomy workflow changes are required. Bayesian dosing tools like DoseMeRx can make mathematical accommodations if the level is not drawn at an exact time, preventing a wasted blood draw.

Meet with me: Dr Kristi Kuper, Director of Clinical Pharmacy, DoseMe

If you would like to learn more about how we can support your transition to AUC-based vancomycin dosing, please email me at kkuper@dosemehealth.com or call (832) 358 3308.

I would be happy to share more insights into how we have supported other institutions through this change management process.