Mythbusting

The Great Vanc-hoax.

There had been some social media buzz about dosing vanco correctly awhile back, primarily based off this post on ALIEM.  The comments section is full of good tidbits as well.  Now, I’m starting to see articles suggesting using CPOE to correctly dose vancomycin.

Cart before the horse much?

This study (403 total patients) showed an insignificant difference in mortality for MRSA bacteremia in an ICU setting when comparing usual care vs weight based vanco dosing.  This one (92 total patients) looked at geriatric MRSA bacteremic patients and also found no difference in morbidity or mortality.  There is literally no study I’ve been able to find that directly looks at morbidity and mortality for weight based vanco dosing in the adult population.

If you want to talk about reaching ideal vanco levels earlier in disease course, that’s fine, but this commonly cited study only looked at the outcomes of 35 patients.   Rather, consider a continuous vancomycin infusion, which to date has more patient-centered data than weight based dosing.

Let’s slow down with these studies showing CPOE makes “appropriate” vanco dosing easier since we already have two studies showing weight based dosing of vancomycin does not make a meaningful clinical difference.

Standard

3 thoughts on “The Great Vanc-hoax.

  1. Hi Patrick!
    I appreciate your comments on what I had previously taken for granted as a relatively non-controversial topic.
    I totally acknowledge that as pharmacists are often the authors of studies, there may be some bias built into the research questions and subsequent conclusions (a bit of job security for clinical pharmacists constructing complex vancomycin dosing regimens.)
    However, I think that this is simply an area that we haven’t had enough data to show the conclusions that logic is pointing to already. Most patients of decent size with normal renal function will have subtherapeutic vancomycin trough levels if everyone gets 1 gram every 12 hours; and we know that subtherapeutic (<10 mcg/mL) vancomycin concentrations are directly correlated with resistant strains of problematic organisms, such as hVISA and VISA (Sakoulas G, Gold HS, Cohen RA et al. Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia. J Antimicrob Chemother. 2006; 57:699-704) and associated with higher rates of treatment failure (Howden BP, Ward PB, Charles PG et al. Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis. 2004; 38:521-8). Furthermore, we know that if patients become infected with one of these resistant strains, there are higher mortality rates (Howden BP, Johnson PD, Ward PB et al. Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2006; 50:3039-47 and Charles PG, Ward PB, Johnson PD et al. Clinical features associated with bacteremia due to heterogeneous vancomycin intermediate Staphylococcus aureus. Clin Infect Dis. 2004; 38:448-51).
    So while I agree that current data are lacking regarding hard patient-centered outcomes when it comes to weight-based dosing, there are documented harms of subtherapeutic dosing (which is often the case with the default 1 gram every 12 hours). Thus it doesn't seem to implausible that we're doing better by our patients if we take the time to put some thought into their vancomycin dosing regimen (but hey, I'm a bit biased as well).
    Respectfully,
    Meghan

    • Hey Meghan!

      Thanks for the reply. Happy to have a good spirited debate!

      Is it really subtherapeutic vanco concentrations that are correlated with problematic organisms, or perhaps that specific resistance and virulence genes are already linked to an elevated vancomycin MIC? As evidenced by Holmes et al (Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates. J Clin Microbiol. 2014 Sep;52(9):3384-93. – http://www.ncbi.nlm.nih.gov/pubmed/25031442), patients with Staph Aureus bacteremia that had SA isolated with an elevated vanco MIC had poor outcomes, regardless of which antibiotic they were prescribed. These findings remain for MSSA with higher vanco MICs.

      In the second study cited (Howden et al, 2004) – there were only 25 patients, 13 of whom were significantly immunosuppressed (on steroids, chemo patients, transplant patients, etc), and only ten had an MIC above 2mg/L. These patients would likely have higher mortality rates to begin with when considering their risk factors.

      While weight based dosing may be the wave of the future, I’d like to see more data before it is rolled out nationwide. In theory, weight based dosing is a great idea – though this does not always play out in practice. If we do see evidence for weight based dosing, I imagine ED bolusing with ICU / floor continuous infusions are not far behind (http://www.ncbi.nlm.nih.gov/pubmed/24887569). I do not think it is fair for small shops such as mine – where we do not have 24/7 staff in the pharmacy (let alone a pharmacist in the ED!) – to be held to the weight based recs that are being SoMe touted without more data to support improved outcomes. Ultimately, long term, I think its reasonable to stock 250mg or 500mg vials of vanco in the ED. However, until there is more evidence suggesting an improved outcome, I have more pressing issues to address (not giving O2 for every chest pain, LR over NS for IVF, timely giving TXA, etc). When there is more convincing lit, I promise to bring it up to the Department!

      Cheers,
      Patrick

  2. Dear Patrick,

    Thank you for publishing this thoughtful post. Those who advocate for weight-based vancomycin dosing don’t alway appreciate the logistical issues of accomplishing that task in community EDs without 24-hour pharmacies (although pre-made vancomycin doses can be purchased all the way up to 2 gm).

    It may be overly-simplistic to call weight-based vancomycin dosing recommendations a “hoax.” Many of the recommendations come from this 2009 guideline: http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=19569969. A separate MRSA guideline also discusses the dosing: http://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.full.pdf+html. While the recommendations for weight-based dosing receive a grade IIIB recommendation, you’ll note that there is a second recommendation to also consider using area-under-the-curve to minimum-inhibitory-concentration ratio (AUC/MIC ratio) as a guiding parameter (also grade IIIB). Updated guidelines on track to be published in 2016 will include much more data on the AUC/MIC ratio and how it impacts clinical outcomes. Without getting too granular here, AUC/MIC ratios > 400 have demonstrated decreased mortality in staph aureus bacteremias and other infections (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623342/ and http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=24867791). A pubmed search will reveal further data on the AUC/MIC ratio; more extensive clinical trials are underway. Troughs, as a standalone parameter of vancomycin ‘efficacy,’ may become a thing of the past.

    And how do we reach these target AUC/MIC ratios? Not with 1 gm q 12 hours. In most cases, the doses needed to obtain the correct AUC/MIC ratio will be higher than traditionally used and weight-based dosing is one way to get us on the right track.

    – Bryan Hayes (@PharmERToxGuy)

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s