March 14th, 2010

MRSA Bacteremia Question Redux — and the “Answer”

testAs noted here, I recently had to answer a question on management of MRSA bacteremia as part of an every-10-year cycle of test-taking.

(For more on that joyous process, read this interesting debate here in the New England Journal of Medicine.)

The question seemed to have no obvious right answer, so I did what one is explicitly allowed to do in this phase of the process — in other words, I asked some experts for their advice.

As a reminder, the case is a guy with positive blood cultures for MRSA (vancomycin MIC 2.0) on hospital day 4 despite receiving vancomycin (trough 15) and having undergone resection of a mycotic aneursym on hospital day 3.

Choices were:  1) continue current vancomcyin dose; 2) increase vancomycin to achieve trough of 20; 3) change to daptomycin; 4) change to linezolid.

Expert Number One said the following:

What a terrible question.  A classic case of “what is the writer thinking and how much does he/she know?” 4 is clearly wrong, but I wouldn’t be surprised to hear that this is what they want.  If the MIC is really 2,  you need a trough of 40, which is not an option, so 2 is wrong.  Given that he is only 5 days out and average duration of bacteremia in this setting is 7 days or so, you could consider 1 with reassessment in 2 or 3 days (but this is not really given here) and with MIC of 2, probably won’t work.  That leaves 3 by default, but with MIC of 2,  there is a significant possibility of heteroresistance to bothvanco and dapto.  A terrible question.  I wouldn’t know how to guess what they want!

And Expert Number Two — who kindly allowed me to cite as Dr. Myoung-don Oh, who is the corresponding author of this paper — generously offered:

I think there are several issues to resolve.

#1. Is the patient failing on VCM therapy? I think it is too early to declare VCM failure in this case. (1)The median duration of MRSA bacteremia(or mycotic aneurysm) is >4 days (2) Even if we choose an optimum antibiotic, MRSA bacteremia would persist if infected focus is not removed). In this case, the aneurysm was resected on HD#3. Therefore, I would rather wait 2 more days to see if MRSA bacteremia persist.

#2. VCM MIC=2 can predict worse prognosis? Previous studies have shown that higher VCM MIC was associated with poor outcome. CID 2008;46:193-200; JCM 2004;42:2398-402; Arch Intern Med 2006;166:2138-44. However, I think we still need further data on this issue, because other variables, especially host conditions and site of infection, also affect the outcome.

#3. With VCM MIC=2(assume that it is confirmed by “gold standard test” rather than E-test), would you like to increase VCM dose? It seems to me that rationale for higher dose VCM is favorable AUC/MIC. Recent guideline (CID, 2009) also recommends VCM trough level of 15-20mg/L, because this gives you AUC/MIC greater than 400 in case that MIC= 1 ug/mL. Problems of this recommendation include (1) correlation between PK/PD parameters & clinical outcome still need further data, (2) increased renal toxicity, (3) AUC/MIC not achievable if VCM MIC>2. (Actually, strength of the recommendation is BIII).

# 4. How about daptomycin for this bacteremic patient? Daptomycin is non-inferior to VCM for initial therapy of MRSA bacteremia. However, if you switch to daptomycin, it’s a salvage regimen. And I am not aware of any clinical data regarding salvage therapy. As VCM MIC =2, I am afraid that cross-resistance between VCM & daptomycin might compromise this salvage therapy.

In conclusion, I’d rather wait for 2 more days with the same VCM treatment.

Which certainly made me feel better.  Since the answer the examiners wanted was daptomycin.

3 Responses to “MRSA Bacteremia Question Redux — and the “Answer””

  1. Jon says:

    Nice discussion Paul, I learned quite a bit from just this one question. Too bad the actual boards doesn’t give such nice feedback on the questions we missed. I’ve always wondered why as I’m sure we would find it invaluable.

  2. Paul Sax says:

    >>Too bad the actual boards doesn’t give such nice feedback on the questions we missed.

    Yep. I did think the discussion in the NEJM on recertification was interesting. My own opinion is that recertification is a good thing, but it’s the “closed book” nature of the exam that makes no sense. Since when are doctors asked to respond to clinical problems without having access to reference materials?

  3. Fatma says:

    very nice Q and discussion I learned a lot, I would like to particepate on such problem.
    though I new the answer but I thought still need to contiue vanc because it is just 1 day after removal of source, second thought is LINEZOLID salvage therapy though it is static but sourc remove and daptomycin is not available

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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Infectious Diseases

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