Dalbavancin Effectively Treats Skin Infections in Patients With Obesity or Diabetes

November 16, 2023

Dalbavancin, a long-acting lipoglycopeptide with activity against gram-positive pathogens, is effective for treatment of acute bacterial skin and skin structure infections (ABSSSI) across body mass index (BMI) strata and in patients with or without diabetes, according to authors of a study in Open Forum Infectious Diseases.

Researchers presented results of a pooled efficacy and safety analysis of 3 clinical trials of dalbavancin as a treatment for adults with ABSSSI.

Data were pooled and summarized separately based on baseline BMI and diabetes status. The data were derived from 2 double-blind, phase 3 trials of dalbavancin (1000 mg IV for 30 minutes on day 1 and 500 mg IV on day 8) vs a comparator treatment (vancomycin 1000 mg IV over 120 minutes every 12 hours for 3 days, with a potential switch to oral linezolid 600 mg every 12 hours from day 4 until treatment completion [10-14 days]; DUR001-301 and DUR001-302) and 1 phase 3b trial of dalbavancin administered as a single dose (1500 mg IV on day 1) or in 2 doses (1000 mg IV on day 1 and 500 mg IV on day 8; DUR001-303).

Post hoc analyses of the study endpoints (≥20% decrease in lesion area at 48 to 72 hours with no rescue antibiotic therapy and investigator assessment of clinical response at end of treatment [day 14] and at day 28) were conducted with use of pooled data in the intent-to-treat (ITT; all randomized patients) and microbiological ITT (microITT; patients in the ITT population with a pathogen identified at baseline) populations.

BMI data were available for 2001 patients (dalbavancin, n=1350; vancomycin, n=651). Diabetes status was available for 2010 patients (dalbavancin, n=1357; vancomycin, n=653); approximately 12% of the participants had diabetes.

Clinical response rates in the overall ITT population 48 to 72 hours after dalbavancin administration decreased with increasing BMI; they were 89.3% (95% CI, 86.3, 92.2), 87.6% (95% CI, 84.6, 90.6), 84.4% (95% CI, 79.9, 89.0), and 78.9% (95% CI, 73.5, 84.2) for the BMI categories less than 25 kg/m², 25 to 30 kg/m², 30 to 35 kg/m², and greater than 35 kg/m², respectively.

Clinical response rates to dalbavancin in the ITT population were 82.4% (95% CI, 76.3, 88.4) for patients with diabetes compared with 86.0% (95% CI, 84.1, 88.0) for patients without diabetes. Clinical response rates were slightly higher at the end of treatment vs 48 to 72 hours from treatment initiation: 90.8% (95% CI, 86.3, 95.4) for patients with diabetes vs 91.6% (95% CI, 90.0, 93.2) for patients without diabetes.

Similar percentages of patients had success regarding these endpoints in the microITT population and in by-pathogen analyses for the 2 treatment groups.

Across BMI strata, the overall percentage of treatment-emergent adverse events (TEAEs) was lower in the dalbavancin group than in the vancomycin group. For both treatment groups, the percentage of patients with TEAEs increased with higher BMI. Among patients with BMI of 35 kg/m²or more, fewer TEAEs were reported for those treated with dalbavancin; 31.7% of patients who received dalbavancin had at least 1 TEAE vs 47.7% of those who received vancomycin.

In their discussion of study limitations, the researchers noted that investigator assessment of clinical success was used, owing to study differences in the definition of programmatically determined clinical success, and that “[A]cross treatment groups and strata, the investigator assessment of clinical success at 28 days was generally several percentage points higher than programmatically determined success based on the definitions.” In addition, the researchers noted that the data reflect patients stratified according to BMI or diabetes status, but not both, and the numbers of patients included (particularly those with diabetes) were insufficient in the vancomycin group to enable meaningful comparisons with dalbavancin.

“The results of this study show that dalbavancin is effective with sustained clinical success rates in patients with obesity or diabetes, with a similar safety profile across patient groups,” the researchers concluded.