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January 30th, 2014

Unanswerable Questions in Infectious Diseases: Persistent MRSA Bacteremia

White_square_with_question_markOk, here’s a favorite of adult ID specialists everywhere — a real tough one. The case goes something like this:

Older person, many medical problems. Probably is on hemodialysis, with the vascular surgeons having some difficulty with access. There’s diabetes, of course, and cardiovascular disease, and oh yeah, a mechanical aortic valve that’s around 10 years old. Some toes are missing from prior surgical treatment of osteomyelitis.

Now? Fever and mental status changes have brought him/her to the hospital, and 100% of the umpteen blood cultures done since admission are positive for MRSA. They remain positive even though the MIC to vancomycin is 1.0 and the trough concentration of the drug is 18.

Since starting on vancomycin, the patient has improved somewhat, but continues to have fevers and, yes, positive blood cultures. Lots of them — it’s been days. Vancomycin MIC is checked again, and it remains unchanged. Maybe even it’s 0.5 this time. An exhaustive search for a removable focus of infection has yielded nothing — no abscess, no valvular vegetations/root abscess, no spinal osteomyelitis, clots. A cardiac surgeon has been consulted, and passes on the opportunity to replace the valve, thank you very much. The dialysis AV fistula is functioning, for now, but is not red or draining.

So the question is this:

With persistent MRSA bacteremia despite “appropriate” vancomycin therapy, should the antibiotics be changed?

Lots of options out there. Linezolid. Daptomycin. Ceftaroline (off label, of course). Combination therapy, with the idea that more should be better, naturally. You could add gentamicin (really?), or rifampin (biofilms!), or do a vancomycin/beta-lactam combination.

Let’s hear from you — vote on these options (as I said, there are lots of them this time), then comment away.

The MRSA bacteremia won’t go away despite “therapeutic” vancomycin — what to do with the antibiotics?

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6 Responses to “Unanswerable Questions in Infectious Diseases: Persistent MRSA Bacteremia”

  1. George Kandelaki MD says:

    Dapto will be reasonable next move, followed by valve replacement if blood cultures continue to be positive.

  2. Federico says:

    My first thought is that since MRSA is still hanging around in the blood steam, there’s have to be a source, even though there’s isn’t any evidence of it. Valve replacement is indicated in this patient because of multiple causes (DBT, MRSA, etc.). Once surgery is performed, continue with Vanco and take blood cultures would be my best approach; wait until results come and hopefully they will turn out to be negative. If not, I would switch to linezolid. This is a very challenging patient Dr. Sax so please make the next one a little bit easier for us:)

  3. I always believed in “Treat the Patient Not the Level”. In this case I would label it as Therapeutic Failure. Trough of 18 but no microbial eradication means ? Biofilm, glycopeptide non permeability , ph lowering sec to lactic acidosis ,bactericidal failure switching to bacteriostatic status quo etc. I would definitely try Daptomycin but maybe 8mg/kg. Hiwever, I’ve been successful pushing Bicarb before Vanco and trying to re culture when patients don’t seem to be worsening clinically.

  4. Chiaying Liu, MD says:

    From my very personal experience, patients with persistent MRSA bacteremia who had experienced vancomycin treatment failure would not respond to daptomycin either. Even under 8-10mg/kg/day. The MIC of daptomycin would increase after vancomycin treatment. So, it may partly explain this phenomenon. Besides, the optimal dose and PK/PD model are not well-established in H/D patients. So, daptomycin may not be the best option, from my personal experience.

    For these patients with persistent MRSA bacteremia, you may need to contact the lab. If the blood culture time to positivity prolonged gradually, then it is more likely that vancomycin therapy may be successful. However, if the time to positivity remained stable, I tried to use linezolid plus rifampicin for 3-4 patients. MRSA bacteremia were successfully eradicated.

  5. Josh Davis says:

    Changing to Daptomycin will increase the daily cost of treatment by over 20-fold, and is unlikely to work based on the RCTs. Adding nafillin would cost a few dollars per day, and may well work (according to >15 in-vitro studies) . . . jury is still out but I am part of team currently running an RCT on this question

  6. Omar Vesga says:

    Sounds familiar: J. Infect. 2009; 59:277-80.

    These papers address really carefully the “vancomycin problem”:

    1. Antimicrob Agents Chemother. 2010; 54:3271-9.
    2. Antimicrob Agents Chemother. 2012; 56:2824-30.
    3. Antimicrob Agents Chemother. 2012; 56:2819-23.

    There are a couple more, but I disliked the methods.

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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Infectious Diseases

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