Pharmacology and the Treatment of Complicated Skin and Skin-Structure Infections

Published - Written by Daniela Lamas

Treating skin and soft tissue infections isn’t the most glamorous job in medicine. But as these infections – ranging from cellulitis to abscess and often accompanied by fever and other signs of systemic illness – lead to nearly 900,000 hospital admissions annually, it’s an essential one. And with the emergence of strains of methicillin-resistant Staphylococcus aureus (MRSA) in the community in recent years, coupled with toxicity and inconvenience of existing antibiotic options – many of which require twice-daily intravenous dosing, such as with vancomycin – there’s a real need for new therapies.

Two recent articles in NEJM offer hopeful news about a potentially less burdensome course of treatment for the estimated 15 million skin and soft tissue infections that occur yearly in the US.

Both studies test drugs whose mechanism of action is similar to vancomyin – the current go-to in our therapeutic armamentarium for skin and soft tissue infection. These semisynthetic antibiotics, called dalbavancin and oritavancin, do their job by blocking steps in how gram-positive bacteria like staph create their cell walls. Because the drugs have a longer half-life allowing  for weekly+ dosing, they could be a desirable option for patients and providers who would no longer be saddled with twice daily dosing of an intravenous antibiotic.

But do they work as well as our mainstays of treatment? To address that question, Dr. Boucher and colleagues enrolled more than 1200 patients with cellulitis, a major abscess or wound infection associated with erythema and drainage or swelling, along with at least one systemic sign of infection such as a fever or elevated white blood cell count. These patients received either three days of intravenous vancomycin followed by oral linezolid for 10 to 14 days, or the study drug – dalbavancin – given as one IV infusion on day one and then again on day eight. Overall, patients randomly assigned to dalbavancin were just as likely to see a response in their cellulitis to those who received the daily intravenous dosing of vancomycin and a week of daily pills.

An accompanying paper describes similar results with the drug oritavancin. In this study, led by Dr. Corey and colleagues, nearly 1,000 patients with cellulitis, abscess or wound infection received either oritavancin in a single dose, or 7 to 10 days of IV vancomycin given twice daily. Once again, those who received the single dose drug were just as likely for their infection to decrease in size in the first few days and to regress fully after the course of treatment.

While these results are promising, it’s not time to say goodbye to vancomycin for skin and soft tissue infections just yet, writes Dr. Henry Chambers, who heads the Division of Infectious Diseases at University of California in San Francisco, in an accompanying editorial.  He notes that both studies were non-inferiority trials, which allow us to conclude that the drugs aren’t significantly worse than vancomycin, but don’t prove that they are more effective. While no safety concerns were identified during the period of study monitoring, the studies assessed only a small number of patients and the medication effects may linger so we don’t know whether they could cause unforeseen reactions weeks or months after administration. Furthermore, the studies do not address how these drugs might work for patients with more severe staph infections such as pneumonia, infections of bones or joints, or infections of the heart valve.

These are key questions to answer, he writes, as these long-acting antibiotics could “profoundly impact how these infections are managed by reducing or in some cases eliminating costs and risks of hospitalization.”

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