IE Management: Antibiotic Treatment

by John Fisher, MD

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    00:00 What do you treat a patient who’s got a penicillin susceptible oral strep or group D strep with a low MIC? What’s recommended in the most recent recommendations in the journal, Circulation in 2015 is either a four-week regimen or a two-week regimen. The four-week regimen is going to include penicillin in high doses. Let me stop there and tell you why. You don’t want to give a moderate dose of an antibiotic in any serious infection. As we say, “Send a man to buy the beer.” Jack up the dose to high dose because these vegetations, some of these bugs are deep within the vegetation.

    00:51 You literally have to soak the vegetation in high doses of antibiotics to get the penetration into it.

    00:58 You’d hate to use a moderate dose of an antibiotic and have the patient fail. You’d have to ask yourself, “Well, did they fail because I didn’t give them enough antibiotic?” When you’re treating serious infections, endocarditis and other serious ones, maximize the dose. Give the maximum dose allowable for that patient. That’s a good infectious disease strategy for many diseases. If they can’t take penicillin G, ceftriaxone is okay. Now, the two-week regimen has got a little addition to it.

    01:34 The two-week regimen calls for high dose penicillin or ceftriaxone. But if you’ll notice, gentamicin is added for synergism. There are some patients who aren’t that sick that you could actually consider a two-week regimen. Most of them are going to get longer therapy but a two-weeker is okay.

    01:58 Now, what if you have a relatively resistant organism and with the MIC a little higher? You’re out with the two-week regimen. You’re going to have to give essentially a four-week regimen.

    02:15 In β-lactam allergic patients, you’re going to have to use vancomycin. Now, what if you have native valve Staph aureus endocarditis? Remember Staph aureus is a very aggressive organism.

    02:37 Let’s say it’s methicillin-susceptible Staph aureus. I’m fine with high dose oxacillin or nafcillin.

    02:47 What’s recommended currently is six weeks of IV therapy. Some of that can be given at home.

    02:55 It depends on the response of the patient. If it’s MRSA or in a penicillin-allergic patient, you’re going to be using vancomycin in high dose for the same duration. Let’s say you’ve got prosthetic valve Staph aureus endocarditis. If it’s methicillin-susceptible then you’re going to use oxacillin or nafcillin plus rifampin plus gentamicin for the first two weeks. If it’s methicillin-resistant, it’ll be vancomycin plus rifampin plus gentamicin for the first two weeks. The duration of therapy is six or more weeks. So, how do you know whether the patient is cured? Well, you’re going to have to stop antibiotics at say, the six-week mark. Wait until the antibiotics clear from the system and then redraw the blood cultures. If the blood cultures are positive, you didn’t treat long enough.

    04:11 Now, this enterococcus, enterococcus, an important point that you can take to the bank is that you can inhibit enterococci with β-lactam antibiotics but you can’t kill it. For the treatment of infective endocarditis, you need bactericidal therapy. You have to kill the organisms.

    04:42 You just can’t kill the organisms with a β-lactam antibiotic, you can inhibit it. But if you only used the β-lactam antibiotic after you stopped therapy, the endocarditis would relapse because you only inhibited the organism. So, what you have to do is provide bactericidal therapy for the enterococcus.

    05:07 That means for the whole week, for the whole length of time that you treat rather, you need to give gentamicin along with your β-lactam antibiotic. So, it’s ampicillin or penicillin plus gentamicin.

    05:22 The duration is going to be four to six weeks. Now, if they are allergic to penicillin then you give vancomycin plus gentamicin. That’s another cell wall agent that only inhibits the enterococcus.

    05:37 Tough bug. Now, the worse scenario is if you have an enterococcus that’s resistant to gentamicin, say.

    05:48 There used to be an adage that cephalosporins and the enterococcus don’t mix. I used to preach that you couldn’t treat enterococcal infections at all with cephalosporins. But we found out in this particular group of patients where we had little to treat them with, you got aminoglycoside-resistant enterococci, that they would actually respond. A large number of them would respond to the combination of ampicillin and the cephalosporins, ceftriaxone. The only downside is if they’re β-lactam-allergic then you’ve really got to come up with some kind of concoction.

    06:38 What they recommend is linezolid or daptomycin, all sorts of things. So, you don’t want your patient to have enterococcal endocarditis particularly one that’s resistant to the aminoglycosides.

    06:54 The duration of therapy is going to be at least and probably more than six weeks.

    07:02 Now, what about surgery? The tendency in the last 15 years or so has been early surgery rather than delayed surgery. I remember many surgeons years ago wanted the patient to have a complete course of antibiotics before they were willing to go in and replace a valve, either replace a native valve or remove a prosthetic valve. The problem with that, it sounds nice but the problem with that is that bad things happen while you’re treating. The things can happen precipitously. So, patients can get sick in a hurry if their prosthetic valve dehisces or something or they get an embolus to their brain. So, there’s a movement to do surgery early rather than late. So, the main indications for early surgery would be somebody who’s got congestive heart failure, somebody who has uncontrolled infection. You’ve got them on the right antibiotic but the blood cultures are still positive. That means that there’s a focus somewhere around the valve that’s shedding bugs into the bloodstream or they’ve had a major embolic event. So, those are the reasons when the surgeons need to go in early.

    08:32 How about the mortality of infective endocarditis? It’s substantial, 15% to 22% die in the hospital.

    08:42 The five-year mortality approaches 40%. It’s less for right-sided infective endocarditis or left-sided native valve due to α-strep. It’s less than 10%, so a good outlook for those patients.

    08:59 But look what it is for Staph aureus on a prosthetic valve, greater than 40%. So, there are really several groups of persons who are at risk for mortality from endocarditis. These include higher age, heart failure, someone who’s had a stroke or other embolic event, and then endocarditis that develops in association with healthcare. In other words, the patient has had some severe problem otherwise leading to them getting infective endocarditis.

    About the Lecture

    The lecture IE Management: Antibiotic Treatment by John Fisher, MD is from the course Cardiovascular Infections.

    Included Quiz Questions

    1. Ampicillin + gentamicin
    2. Penicillin G + ampicillin
    3. Vancomycin + gentamicin
    4. Vancomycin + ampicillin
    5. Ceftriaxone + vancomycin
    1. 6 weeks of intravenous therapy
    2. 6 weeks of oral therapy
    3. 2 weeks of intravenous therapy
    4. 4 weeks of combined oral and intravenous therapy
    5. 6 months of intravenous therapy
    1. Vancomycin
    2. Vancomycin + gentamicin
    3. Nafcillin + gentamicin
    4. Ampicillin + gentamicin
    5. Vancomycin + ceftriaxone
    1. New or worsening cardiac murmur
    2. Congestive heart failure
    3. Lack of effective antimicrobial therapy
    4. Embolic stroke
    5. Partially dehisced unstable prosthetic valve
    1. A 70-year-old with baseline congestive heart failure who develops Staphylococcus aureus prosthetic valve infective endocarditis
    2. A 28-year-old intravenous drug user with right sided infective endocarditis
    3. An otherwise healthy 35-year-old with Enterococcus infective endocarditis
    4. An otherwise healthy 70-year-old with native valve Streptococcus viridans infective endocarditis
    5. An asthmatic 50-year-old with endocarditis by a fastidious organism

    Author of lecture IE Management: Antibiotic Treatment

     John Fisher, MD

    John Fisher, MD

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