Two drugs may make skin structure infections easier to manage

Two new drugs may make acute bacterial skin and skin-structure infections easier to manage, including on an outpatient basis, according to 2 new studies.

In the first paper, researchers reported on 2 trials that randomized a total of 1,303 patients at sites around the world to either vancomycin with the option to cross over to oral linezolid or dalbavancin. Dalbavancin was administered at a dose of 1 g for 30 minutes on day 1, followed on day 8 by 500 mg given intravenously for 30 minutes. Vancomycin was given at a dose of 1 g (or 15 mg per kg of body weight) for 120 minutes every 12 hours for at least 3 days, with an option to switch to oral linezolid, at a dose of 600 mg every 12 hours. The research was funded by the drug's manufacturer, Durata Therapeutics. Results appeared June 5 in the New England Journal of Medicine (NEJM).

In a pooled analysis of both trials, 525 of 659 patients (79.7%) in the dalbavancin group and 521 of 653 (79.8%) in the vancomycin-linezolid group had an early clinical response, defined as cessation of spread of infection-related erythema and the absence of fever at 48 to 72 hours (weighted difference, −0.1 percentage point; 95% CI, −4.5 to 4.2). In individual analyses of the trials, the early clinical response rates were not significantly different between the drugs. The researchers concluded that dalbavancin was noninferior to vancomycin-linezolid in each trial. For patients infected with Staphylococcus aureus, including methicillin-resistant S. aureus, clinical success was seen in 90.6% of the patients treated with dalbavancin and 93.8% of those treated with vancomycin-linezolid.

Fewer patients in the dalbavancin group reported adverse events than those in the vancomycin-linezolid group, and most events were mild and thought to be unrelated to the treatment. The most common treatment-related adverse events were nausea (2.5% in the dalbavancin group and 2.9% in the vancomycin-linezolid group, P=0.062), diarrhea (0.8% and 2.5%; P=0.02), and pruritus (0.6% and 2.3%; P=0.01).

The researchers noted that results were robust in patients with major abscess, cellulitis, or wound infection and in outpatients. “Patients included in the study were ill enough to require intravenous therapy and hospital referral or admission and had a high rate of fever,” the researchers wrote. “Approximately 50% of the patients in our study met the criteria for the systemic inflammatory response syndrome.”

Dalbavancin was recently approved by the FDA to treat acute bacterial skin and skin-structure infections caused by susceptible bacteria, including S. aureus (including methicillin-susceptible and methicillin-resistant strains) and Streptococcus pyogenes.

A second study published in the same issue of NEJM found that a single dose of oritavancin was noninferior to twice-daily IV vancomycin for acute bacterial skin and skin-structure infections caused by gram-positive pathogens.

Funded by the Medicines Company, the double-blind trial randomized 954 adults with acute bacterial skin and skin-structure infections to either a single IV dose of 1,200 mg of oritavancin or IV vancomycin twice daily for 7 to 10 days. All 3 efficacy end points met the prespecified noninferiority margin: early clinical evaluation, 82.3% vs. 78.9% (95% CI, −1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% vs. 80.0% (95% CI, −5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI, −0.5 to 8.6 percentage points). Efficacy was similar when assessed by strain of pathogen, including methicillin-resistant S. aureus. Adverse event rates were also similar, although nausea was more common among those treated with oritavancin. Oritavancin has not yet been approved by the FDA.

An editorial related to both studies commented that while both drugs have been available since the 1990s, they could transform the treatment of acute bacterial skin and skin-structure infection.

“Neither antibiotic is more efficacious than vancomycin, but either agent is certainly easier to administer,” the editorial stated. “These agents make it possible to treat patients with complicated skin and skin-structure infections, who might otherwise require hospitalization, on an outpatient basis without compromising efficacy and without the need for laboratory monitoring or an indwelling intravenous catheter. This approach could profoundly affect how these infections are managed, by reducing or in some cases eliminating costs and risks of hospitalization.”