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Long-Acting Lipoglycopeptide Antibiotics for ABSSSI

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Segment Description: Christian Sandrock, MD, MPH, FCCP, discusses the emergence of newer long-acting lipoglycopeptide antibiotics for the treatment of acute bacterial skin and skin structure infections.

Christian Sandrock, MD, MPH, FCCP: The glycopeptide class, which vancomycin (Vancocin) is a poster child for, has certainly been around for a while. Over the past, 20 years plus, there has been a development of the lipoglycopeptides—hence the name lipo- shows that they have a long lipophilic side chain that provides a number of different features associated with them. From a clinical perspective, those features are noted in terms of much more improved or lower what we call MICs, minimum inhibitory concentration levels. For example, where vancomycin may have an MIC of 1 to Staphylococcus aureus, this will be 4-fold lower, 0.012 or lower in some cases. So, to say you have more activity, you just have much lower MICs, which provide better killing when you have marginal tissue distribution, which can happen in necrotic and abscess-based areas. So, it allows for certainly that.

Another feature is with that lipophilic side, or the lipoglycopeptide cases, you actually have a very long half-life. Very often, that half-life is greater than 7 days, so you can give a single dose of this antibiotic IV and then walk away, and that can be the equivalence of 7, even 14 days of IV and/or oral therapy. So, again, it allows a nice option. Rather than having someone come in, getting the standard of care of vancomycin twice daily, IV, you can give them a single dose of dalbavancin. They get their dose, they’re now sent home, and that’s the equivalent of 14 days of IV vancomycin. It does provide some flexibility with these patients, where you can choose to have a patient that’s going to either be non-compliant or their disease is more complicated for oral therapy. But you don’t necessarily have to admit them, and you can send them home.

Now, the clinical trials looking at the lipoglycopeptide class did actually select for moderate severity of illness. So, again, we mentioned some of those, but in the dalbavancin trials, 85% of those patients had a fever, 40% had a leukocytosis, many of them met SIRS criteria based on a New England Journal of Medicine article. Many of them actually were treated as outpatient therapy through the ED. So, we know from the clinical trial, we have some support that these patients do well at home. What we do at our facility is 2-fold. One is, we always get blood cultures on everybody, and we have a mechanism to call them back should something change. Secondly, we make sure that within 5 days, they have a follow-up to have their wound checked, to make sure they’re actually having regression of their disease and improvement, so we know that things are better. That’s often the big issue—yes, you can give them this antibiotic and send them home, but you need that follow-up, so that they can come back and actually get evaluated to make sure the antibiotic is working appropriately. That’s really the big trick for us. We have a great avenue for having them follow-up. I will tell you that many of these patients never show up because they’re just a difficult group to manage. And they really, again, are often homeless, living outdoors, no stable address, active psychiatric and drug use. They just don’t like to come back even if you give them an appointment in 5 days. They just sometimes don’t show up.

The dosing and administration for the lipoglycopeptides is actually really easy. So, again, the glycopeptide class, like a vancomycin, you’re used to giving a single dose, say for example, a gram twice daily, if you have normal kidney function. That dose is usually run in over an hour or longer and it’s IV. The nice thing with the lipoglycopeptide class like dalbavancin; you actually give a single dose once. So rather than a dose twice a day for 14 days, you can give a single dose once, for example, 1500 mg. Instead of it being run in over an hour, it’s actually run in over 30 minutes, and that’s it and you’re done, and you can let the patient go home.

In the studies, that was equivalent of 14 days of IV vancomycin, plus or minus oral therapy, depending on the patient. It’s basically a single dose, providing 14 days of care of therapy, which is again really great. No need to have them admitted and have IV therapy twice daily—no need to worry about compliance and oral therapy when they go home. Again, those patients had a moderate level of severity of illness, with greater than 90% of those patients having some systemic sign of illness, to be enrolled in that study. It actually provides a nice option of a single dose over 30 minutes where they can then be sent home.

There are 2 cases I remember recently of successful outpatient therapy with a long-acting glycopeptide—in this case dalbavancin—at our institution. Recently we had one gentleman who came in, had a moderate abscess on his shoulder. This was an area where he actively was using methamphetamines intravenously. It was about 6 to 7 cm. We did a debridement in the emergency department, admitted him to the medicine service because, unfortunately, with his methamphetamine use he was having active psychiatric disease. Over the ensuing 2 days, he received IV vancomycin, his lesion continued to slowly get better, but, again, he had active psychiatric disease. By 48 hours in the hospital, he was actively suicidal. Generally, that again means he’s not going to be discharged. Even though his skin and soft tissue infection was slowly improving, he was not able to be discharged for his psychiatric disease. We did get lucky in this case where a bed opened up at one of our long-term psychiatric facilities. Unfortunately, that place does not administer IV antibiotics. So, it became a nice opportunity to then transition from IV vancomycin. We gave him a single dose of dalbavancin. That then allowed us to remove the IV and no longer administer IV therapy for his skin and soft tissue infection, and he was able to get the appropriate psychiatric care and detoxification that he needed associated with that. Again, he was admitted but it allowed for an early discharge.

The other patient, which we thankfully have a few per week—and this is a standard patient we will have at UC Davis—is it’s a younger gentleman, early 20s, again usually living outdoors, doesn’t have a stable address, develops a skin and soft tissue infection. This one was actually on the buttocks, and he was mostly sleeping outside, also actively smoking and injecting methamphetamines. The abscess on the buttock was drained by surgery in the emergency department, was well packed with care, and he had access to come back within a few days to get his wound changed on a regular basis in the surgery clinic. But, again, he had really no other comorbidities other than his social issues that limited him; stable blood pressure, normal lactate, was febrile when he came in, but during his time in the emergency department, his fever reduced.
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Big advances in treatment can't make up for an inability to stop new infections, which number 5,000 per day worldwide.