HIV and ID Observations

As 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.