January 22nd, 2019

Unanswerable Questions in Infectious Diseases — Treatment Duration in Endocarditis: 4 Weeks, 6 Weeks, Other?

National Library of Medicine

Time to get back to some tough clinical decisions. It’s been a while.

We’ve done The Abdominal Collection and Duration of Antimicrobial Therapy, Persistent MRSA Bacteremia, and The Positive Cultures for Candida in an ICU Patient.

However, that series of posts appeared here in early 2014, which means it’s been 5 years with no “Unanswerable Questions.”

Lest you think that all Unanswerable Questions have been answered — ha — here’s another one, inspired by a flurry of papers recently on a favorite topic, duration of antimicrobial therapy.

To summarize virtually all of them — shorter is usually as good, if not better, than longer. Nice editorial here.

Before we get to the case, an up-front apology that the question might seem simple. But I assure you, the answer is anything but straightforward. Bold prediction: there will be a substantial divergence in responses.

Additionally, while the question may not seem like such a big deal, there are many interested parties eagerly awaiting our answer — including our hospitalist, cardiology, and primary care colleagues, diverse insurance plans, homecare companies, outpatient pharmacies, and skilled nursing facilities. Most importantly, our patients and their families care a lot, too.

And even though the correct answer to “How long should I treat?” is “Long enough” (thank you, Bob Rubin!), this doesn’t change the fact that consulting services really want to know a precise answer. Ironic, huh?

Here’s the case, an amalgam of many seen over the years:

A 52 year old man is admitted with fever. On exam, he has a temperature of 101.5F and a loud systolic murmur. Two sets of admission blood cultures grow methicillin-sensitive Staph aureus. A cardiac ECHO shows a bicuspid aortic valve with a 0.5-cm vegetation.

He is treated with oxacillin; follow-up blood cultures are negative by hospital day 3, and fevers slowly resolve. A peripherally inserted central catheter (PICC) is placed on hospital day 5, and cefazolin replaces oxacillin in anticipation of discharge home on IV antibiotics.

The patient, the medical team, the homecare company, and your OPAT colleagues all await a specific “stop date” for the IV cefazolin.

The question:

If he has a clinically stable course (no further positive cultures, no recurrent fevers, and no metastatic sites of infection), how long would you treat him with intravenous antibiotics?

Before you answer, you’re welcome to look at the guidelines — this is an open-book blog, after all:

Or, you could just wing it based on your clinical experience and judgment, or cite the POET study if you’re feeling cutting edge. Clock starts the day of the first negative blood culture.

And please defend your choice in the comments section, especially if you choose option 4!

How long would you continue intravenous antibiotic therapy?

View Results

(Apologies to Drs. Wald-Dicker and Spellberg for the Days-of-the-Week Units.)

16 Responses to “Unanswerable Questions in Infectious Diseases — Treatment Duration in Endocarditis: 4 Weeks, 6 Weeks, Other?”

  1. Louie Katz says:

    Old docs treat longer?

  2. Don Branam says:

    I voted for 4 weeks, but I would have made a strong push for the clock to start on day 1 of anti-Staphylococcal therapy instead of the first negative culture. There’s no data to support the “first negative culture” standard.

    • Paul Sax says:

      Hi Don,
      Thanks for your comment!
      1) I think the “no data” comment can apply to lots of things that we do!
      2) Consider one of those patients with persistent MRSA bacteremia. Really don’t start the clock at first negative blood culture?
      Paul

      • Don Branam says:

        No, persistent MRSA bacteremia would be a game changer. Then I would be worried about metastatic foci, looking at MICs, obsessing over vancomycin troughs, and…down the rabbit hole I go.

  3. Adolfo - ID -Bolivia says:

    In POET trial the evidence is for MSSA instead MRSA, I agree with that

  4. MN MD says:

    Any discussion of a surgical plan?

  5. Goffredo ID Italy says:

    Why 6 weeks in a native valve?

  6. Steve Martyak says:

    Goal is to prevent mortality and morbidity (M&M…embolization and valvular destruction/heart failure)

    Size of the vegetation during/after treatment seems to correlate with M & M.

    Duration of treatment would be based on afebrile period AND its impact on the size of vegetation noted on repeat TE’s.

  7. Dick Ellison says:

    Paul – great topic!! You didn’t leave an option for a modified POET’s approach 4 wk IV plus 2 weeks PO for those of us who are impressed by that study’s results but a leary of taking the plunge to giving only 17 days of IV treatment

  8. Sandra Criales says:

    Hello,
    Curious thing
    I answer almost automatically 6 weeks but We all known deeply in our souls that the guidelines … ( here 3 for example) talk about 4 weeks after negatives cultures… I think that maybe The British guidelines , talks 4-6 weeks for sensitive staph. I believe just that we are feeling just playing “safer” with more atb time but … often forgetting the side effects of atbs.. opinions ?

  9. Larry Kurz, M.D. says:

    Shouldn’t we consider those aortic valve leaflets, constantly moving in the high pressure maelstrom of the aortic root? Shouldn’t we marvel that antibiotic molecules can even get into such an area? In the absence of hard data, I would vote for a longer period of treatment.

  10. JOSEP CUCURULL says:

    I answer 2 weeks iv plus vo treatment, because I think antibiotic blood concentrations are enough with a good vo antibiotic when bacterial load is lower after two weeks treatment, I prefer a longer vo treatment if necessary in relation to the evolution of the vegetation

  11. DL MD says:

    Any consideration of the difference in adherence between IV and PO regimens? Unless in a post-acute care setting with confirmed administration, I would wonder about actual vs ideal concentrations achieved.

  12. MGuzman says:

    I will treat 4 weeks. I will be worried of the presente of resístance to cefazolin ni some MSSA strain.
    In that case, Oxacillin should be the treatment for the 4 weeks

  13. Erin Barnes says:

    6 weeks. It seems we figured out the 4 weeks thing from the early studies with penicillin when we found out how short was too short. Is there really a difference between 4 and 6 weeks? Probably not, particularly in such a straight forward case. But this kind of case seems the rare gem. Usually the bacteremia is much longer and the vegetation much bigger. Finally, I have been burned by S aureus enough with it playing possum and then re-emerging (admittedly more in the bone and joint realm) that I tend to almost always favor longer over shorter courses when it is involved.

  14. Peter McKellar says:

    I never want to find out how long was not quite long enough.

Leave a Reply

Note: This is a moderated forum. By clicking on the "Submit Comment" button below, you agree to abide by the NEJM Journal Watch Terms of Use.

Our physician bloggers cannot respond to requests for personal medical advice, and recommend patients discuss health issues with their individual physicians.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

Learn more about HIV and ID Observations.