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Preventing MRSA from Becoming VMRSA

Miller, Daniel G. MD

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doi: 10.1097/01.EEM.0000490511.14703.27
    All three of these lipoglycopeptide antibiotics are huge molecules. But dalbavancin and oritavancin have long fat-soluble side chains, which increase their volume of distribution and gives them much longer half-lives than vancomycin.

    Oritavancin and dalbavancin have been around since the 1990s, but chances are you have never prescribed either in your ED. That could change soon. Like vancomycin, these lipoglycopeptides are effective against MRSA and other gram-positive bacteria. What distinguishes these drugs from vancomycin, however, is also the source of their novel utility.

    They have incredibly long half-lives. (See figure.) Previously, two options were available if a patient needed IV antibiotics for cellulitis: hospital admission or a PICC line and an arrangement for home infusions. Now, we have a third option: Infuse one of these newer lipoglycopeptides, and your patient can go home with a week's worth of MRSA-effective antibiotic onboard. Where do you think such infusions are going to happen? The ED, of course.

    Acute bacterial skin and skin structure infections (ABSSSIs) are estimated to cause more than 15 million infections and result in more than 800,000 hospital admissions each year. Thanks to the spread of MRSA into the community and other factors, these numbers are on the rise. Combine ABSSSI prevalence with increasing pressures on emergency physicians to keep patients out of the hospital, and it seems likely that EPs are going to start having to use these drugs. The next time you call your hospitalist to admit a cellulitis patient for IV therapy, she might ask why you won't just give a dose of oritavancin and discharge the patient. It's not an unreasonable suggestion, and, in fact, it just might be the best thing for the patient. But there are some things you'll need to know before you adopt this practice.

    Dosing and Half-lives

    The Good News

    Oritavancin and dalbavancin appear to work just as well as vancomycin for ABSSI. The New England Journal of Medicine published two trials in 2014 assessing these antibiotics' efficacy against ABSSSI. One found that dalbavancin, when given in two IV doses one week apart, was non-inferior to a 10- to 14-day course of twice daily vancomycin or IV vancomycin for three days followed by a transition to oral linezolid for completion of the 10- to 14-day course. (N Engl J Med 2014;370[23]:2169.) The other trial found a single 1200 mg dose of IV oritavancin to be non-inferior to a seven- to 10-day course of twice daily IV vancomycin. (N Engl J Med 2014;370[23]:2180.) The results of the latter study were reproduced in a 2015 trial. (Clin Infect Dis 2015;60[2]:254.) Now these were industry-sponsored non-inferiority trials, so some skepticism is warranted, but the data appear rather convincing.

    Causes for Caution

    Such outpatient treatment plans are obviously not appropriate for patients with other problems that necessitate hospital admission. Along those lines, oritavancin will falsely elevate aPTT and INR measurements and increase Coumadin levels. This might not be the best option for patients needing tight control of heparin or Coumadin therapy, and it is worth noting that oritavancin appears not to work as well as vancomycin for osteomyelitis.

    We also have to consider the financial aspects. A single, 1200 mg dose of oritavancin costs more than $2,000. The drug cost will get folded into the DRG charge for the later hospital admission if a patient is admitted within four days of oritavancin administration. This will eat up most of your hospital's reimbursement for the admission, so you'll be sure to hear about it on Monday morning from your hospital's quarterback.

    These are not magic bullets. Studies supporting its use had about a 10 percent failure rate. As with any treatment for ABSSI, it is important to get your patient followed up to make sure the infection has resolved.

    The Dark Side

    Antibiotics with a long half-life are not a new concept. This is the same reason that we can give a five-day course of azithromycin to treat infections that otherwise require one-to-two-week courses of other antibiotics. Long terminal elimination half-life drugs maintain their concentration high enough for long enough to cure the patient. But there's a catch. These antibiotics don't drop to undetectable serum levels as soon as they stop fighting the infection; rather, the concentrations gradually decrease. This means your patients will have several days while these drugs are still in their system at levels below the minimum inhibitory concentration, creating a great environment to breed resistant organisms.

    We saw the emergence of macrolide resistance with the increased use of azithromycin, and it is quite possible oritavancin and dalbavancin use could breed vancomycin-resistant strains of MRSA in the same way, as Ryan Radecki, MD, pointed out in his blog EM Literature of Note. (“Let's Make MRSA Stronger,” 2014; It is of vital importance that we guard against indication creep with these new agents. Strongly consider an alternative if a viable one exists.

    A recent study found that 42 percent of treating physicians stated a need for IV antibiotic therapy as the only reason for admission to the hospital. (West J Emerg Med 2015;16[1]:89.) Some experts have cited this as evidence that we should be using these long-lasting lipoglycopeptides more often. I would put it in the opposite way, however. That study tells me that these are the wrong drugs most of the time. If there is another indication for admission, then admit the patient and select a different agent.

    Responsible ED Use

    If the thought of vancomycin-resistant MRSA isn't enough to scare you off of these antibiotics completely, it's at least a reason to think twice before reaching for them. They have a relatively narrow indication, and emergency physicians will likely be the group that protects against or invites in the indication creep. Go through the following checklist if you are considering giving one of these drugs to make sure you are prescribing it responsibly:

    • Does the patient have an ABSSSI that is known or strongly suspected to be caused by staph or strep species?
    • Are IV antibiotics your only viable option in this patient?
    • Are you confident that your patient does not have osteomyelitis?
    • Can your patient go home after the infusion?
    • Can follow-up can be arranged to ensure complete resolution of infection?

    If you answer no to any of these questions, you should probably pick another antibiotic so we do not have to change MSRA to VMRSA.

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