March 5th, 2010

Test Question on MRSA Bacteremia

test_takingI just happened to be taking a test the other day — something I do for fun every now and then, say every 10 years or so — and I came across this question (slightly condensed/changed to protect the innocent):

Man with history of IDU admitted with fever, has bacteremia due to MRSA (MIC 2 mcg/mL confirmed by E-test). Found to have mycotic aneurysm of superficial femoral artery.  Aneurysm is resected surgically on hospital day 3. On vancomycin 1 gm IV q12 hours, vancomycin trough is 15 μg/mL.  Blood cultures drawn on hospital day 4 turn positive the next day; patient is subjectively improved but still febrile. WBC has declined from 16k to 11K.

What is the best next step?

1. Continue current rx
2. Increase vancomycin dose to achieve trough of 20 mcg/mL
3. Change vancomycin to daptomycin
4. Change vancomycin to linezolid

So what’s the answer?

Does anyone really know what the best thing to do here is?  For the record, I got it “wrong.”

17 Responses to “Test Question on MRSA Bacteremia”

  1. Jon says:

    Tough one Paul. Vancomycin effectiveness is likely dependent on MIC even in the lower ranges, but least by current CLSI standards, this strain is considered sensitive and the trough is appropriate. Not sure that this pt yet fits the definition of persistent bacteremia. I’d continue vancomycin at the current dose with a low-threshold for going to the bullpen.

  2. Michael Samarkos says:

    If MIC for vanco is 2 mcg/ml, then AUC/MIC(for a trough of 15)should be around 200. Although typically this is OK (it is >125) for problem pathogens (like staph aureus) some suggest that AUC/MIC should be 400. This is practically impossible with MIC=2 !!!
    Therefore in my opinion the best next step is changing to daptomycin (it is OK even if the patient has right sided endocarditis !).
    PS What is the correct answer according to the examiners ?

  3. Paul Sax says:

    >>PS What is the correct answer according to the examiners ?

    Jon and Michael, correct answer coming soon — I want to wait for a few more responses.

  4. todd ellerin says:

    Tough case. It is not unusual to see recurrent MRSA bacteremia at day 4 and sometimes even longer (even without intravascular seeding) but in recent years we have witnessed an MIC creep. At my hospital most MRSA isolates (>70%) have an MIC>1 and roughly 20% have MIC>2. Although this strain is still considered susceptible by CLSI standards, as Michael pointed out it is not possible to achieve a high enough AUC/MIC ratio with vanco when the MIC is 2. Even when the MIC is 1, the vanco trough needs to be in that 15-20 range to achieve an acceptable ratio. Since this patient has a serious intravascular MRSA bactermia and recurrent bacteremia at day 4, I agree with switch to Daptomycin. We know through observational studies that pts with MRSA bacteremia with MIC b/w 1-2 who are treated with vanco don’t do as well as those with lower MICs. What we still don’t know is whether switching to other agents improves outcomes. Switching to Linezolid is problematic in this scenario since it is bacteriostatic. It is also worth noting that Dapto resistance seems to occur more commonly in the pts who have higher vanco MICs.

  5. Paul Sax says:

    >>…It is also worth noting that Dapto resistance seems to occur more commonly in the pts who have higher vanco MICs.

    Exactly …

    Anyone see this case series?

    Clin Infect Dis. 2009 Aug 1;49(3):395-401.
    Salvage treatment for persistent methicillin-resistant Staphylococcus aureus bacteremia: efficacy of linezolid with or without carbapenem.

  6. Jon says:

    It’s a provocative study, but this pt would not have met the study entry criteria. He’s been bacteremic for 4 days and only 1 day after the main foci of infection’s been removed. Would you consider him a vanco failure at this time?

  7. Paul Sax says:

    …but this pt would not have met the study entry criteria.

    Absolutely. However, given the issue of heteroresistance between vanco and daptomycin, the Korean case series, and admittedly my very-anecdotal experience, I would not be surprised if we start using more linezolid in cases that DO have persistent MRSA bacteremia, even though the drug is not cidal.

    In fact, I remember hearing from a noted expert in the field that vanco-resistant MRSA might have increased susceptibility to linezolid in vitro. (Can’t find a reference on this after a brief search.)

  8. CM says:

    Continue vanco. Not convinced that bacteremia pod #1 represents a failure. Except fever, other parameters are improved. Fever may or may not be related to the bacteremia. Plus, vanco creep likely means dapto creep. Linezolid likely problematic as static and its myriad side effects that manifest with any length of time.

  9. Kimon Zachary says:

    Switch to daptomycin (though above points re: concordance of reduced susceptibility to vancomycin and daptomycin are well taken), ask lab to check MIC for daptomycin and for telavancin…

  10. Wissam says:

    According to the IDSA endorsed new Vancomycin dosing guidelines you should change Vancomycin to something else in this case as with MIC of 2 cannot achieve target AUC/MIC. What the guidelines do not tell us is which method to measure MIC should we adopt, and what to swich to? E-test MIC have shown to be one dilution higher than broth microdilution in at least a couple of studies. Is Vitech/Phoenix MICs ok? How do they compare to broth microdilution and E-test?

    • Paul Sax says:

      E-test MIC have shown to be one dilution higher than broth microdilution in at least a couple of studies.

      Have heard this too. So not sure what the question means when it says, “confirmed by E-test.”

  11. Eli Opacich says:

    Good commentary so far. I would not play around with MRSA bacteremia with an MIC of 2. What to switch to? Daptomycin would be my first choice although there is little definitive data to determine what the go to drug should be (dapto, linezolid, telavancin). What’s the “right” answer?

    • Paul Sax says:

      What’s the “right” answer?

      Eli, am waiting for at least one response (perhaps from a noted expert?) before I divulge it. Thanks for your comment.

  12. Vernon Horst says:

    While we wait for the definitive answer, I’ll add in my 1/2 cent as a 2nd year medical student, confirmed by a conversation with the ID guru at my medical school.

    3. Change vancomycin to daptomycin.
    Explanation (given by ID guru): the patient likely has right-sided endocarditis, and Daptomycin is indicated for endocarditis. If the MIC is less than 2, you can increase Vancomycin to a maximum trough of 15-20 mcg/ml. Since the MIC is 2, you probably want to bring out the “big guns” with Dapto. Additionally, linezolid is bacteriostatic, while dapto is bacteriocidal. All these combined leads us to concur that daptomycin is the DOC for this patient.

    What do the examiners say?

  13. Paul Sax says:

    For those who chose daptomycin, 12% (.65 x .19) of ID doctors agreed, at least as of 2006!

    Note that this was a bit before the comparative study:

  14. Enrique Naveira-Abeigon says:

    Yo personalmente cambiaría a daptomicina, y si la función renalestá comprometida a Linezolid apoyada o no con un Carbapenen

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Paul E. Sax, MD

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