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Why Vancomycin Dosing Standards Are About to Change

February 13, 2020
Why Vancomycin Dosing Standards Are About to Change

The new consensus guidelines on vancomycin dosing are due to be released online in March 2020. Is your organization aware of them and starting to prepare?  Have you read any of the peer-reviewed studies that have driven adoption of the guidelines?  If not, it’s not too soon to become educated about the guidelines and begin taking steps to ensure that you can meet the new standard of care. Below is a brief background summary of the draft guidelines and likely recommendations (available at the ASHP website).

Why Vancomycin Dosing Guidelines Are Changing

Vancomycin has become ubiquitous in hospital environments, prescribed to millions of patients each year to treat or prevent serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other susceptible Gram-positive organisms.

However, acute kidney injury (AKI) is a serious problem when administering vancomycin. While definitions and estimation methods vary, one meta-analysis showed that the prevalence of vancomycin-associated AKI is between 5% and 43%, and another showed that patients on vancomycin have a relative risk of AKI of 2.45. The risk of AKI has been shown to increase in a dose-dependent manner as vancomycin concentrations rise.

Current vancomycin dosing guidelines – in place since 2009 -  recommend measuring serum trough levels to determine whether the dosage is within the narrow therapeutic range for this drug, and recommend trough concentrations greater than 10 mg/L for most infections and 15-20 mg/L for more complex infections.

Trough levels, however, have proven to be less than ideal in walking the fine line between efficacy and toxicity. Since the 2009 guidelines were published, a growing number of peer-reviewed studies have demonstrated that dosing to these trough targets puts patients at undue risk of nephrotoxicity and occasional risk of treatment failure. Vancomycin-related acute kidney injuries (AKIs) have been estimated to impact more than 40,000 U.S. patients each year, with about 10,000 people getting more serious Stage 2 or 3 AKIs.

Additional studies have shown that using area-under-the-curve (AUC) methods in place of trough-based dosing provides more precise vancomycin dosing that reduces the likelihood of AKIs without compromising efficacy. A prospective study found that a therapeutic dose could be achieved 70% of the time using AUC compared to 19% of the time when using trough concentrations. Those findings led the Infectious Diseases Society of America (IDSA), American Society of Health-System Pharmacists, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists to develop consensus guidelines that are due to be released online this March and in print this June.

Expected Recommendations

Key recommendations in the new guidelines include AUC-guided dosing and monitoring, with a target AUC/MIC ratio of 400 to 600 for both adults and children, implemented in one of two ways:

●     The preferred approach is to use Bayesian software programs with pharmacokinetic models to estimate AUC based on one or two vancomycin levels.

●     Alternatively, AUC can be calculated using first-order PK equations based on the collection of a steady-state concentration one to two hours post-infusion and a second concentration at trough.

Upcoming Topics

This post has covered the rationale for the change in vancomycin dosing guidelines. In future posts, we’ll cover the following topics:

●     How Will Bayesian-Guided AUC Monitoring Work in Practice?

●     How Will AUC Monitoring With First-Order PK Equations Work in Practice?

●     Deciding Between Vancomycin AUC Monitoring Approaches

For more information on the new guidelines and related topics, reach out to us today.

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