Investigational IV Delafloxacin Effective in Obese Patients with ABSSSI
SAN DIEGO, CA—Delafloxacin (DLX), an investigational broad-spectrum fluoroquinolone antibiotic, may offer an alternative treatment to vancomycin/aztreonam (VAN) in obese patients with acute bacterial skin and skin structure infections (ABSSSI), reported authors of a Phase 3 trial presented at IDWeek 2015.
An added benefit: no dose adjustment or monitoring are required, according to the coauthors.
Early objective responses at 48–72 hours showed “comparable clinical activity to vancomycin” for patients administered DLX, reported study coauthor Sue Cammarata, MD, of Melinta Therapeutics in Lincolnshire, IL. “At followup, a higher percentage of obese patients in the delafloxacin group experienced a cure than did obese patients in the vancomycin/aztreonam group.”
“Obese patients in the clinic are generally therapeutically more challenging than non-obese,” she stated. Previously, a Phase 2 trial found that in patients with a body mass index ≥30kg/m2 who had ABSSSI, delafloxacin showed statistically better outcomes when compared with vancomycin/aztreonam.
In the Phase 3 trial, 660 adults with ABSSSI, defined as lesion size ≥75cm2 and ≥2 signs of systemic infection, were randomly assigned to receive intravenous delafloxacin 300mg twice daily or vancomycin/aztreonam 15mg/kg with aztreonam for 5–14 days. (Aztreonam was discontinued if gram-negative infections were not found, the coauthors reported.)
Among these patients, 214 had BMI ≥30kg/m2, 54% were male, mean age was 48.3 years, and 17% had diabetes. At baseline, the average erythema area was 417 cm2. Those who were obese were older, more likely to be diabetic, and have larger lesions, cellulitis, and lower extremity lesions when compared with non-obese patients, the investigators reported.
The primary endpoint was ≥20% reduction in lesion size at 48–72 hours. The secondary endpoint was investigator-assessed response based on resolution of signs and symptoms, defined as “cure,” at follow-up and late follow-up visits.
At 48 to 72 hours, 75% (90/120 obese patients) in the delafloxacin group had an objective response, compared with 74.5% (70/94) in the vancomycin/aztreonam group; delta (95% confidence interval [CI]: -0.532 (-12.51, 11.05). Investigator-assessed cure at follow-up was 56.7% (68/120) in the delafloxacin group and 44.7% (42/94) in the vancomycin/aztreonam group (delta -11.986 [-25.08, 1.54]; at late follow-up, the outcomes were 71.7% and 57.4%, respectively (delta –14.220 [–26.90, –1.34].
In the microbiologically evaluable population, microbiological response at last follow-up in patients with methicillin-resistant Staphylococcus aureus (MRSA) at baseline was 100.0% (22/22 obese patients) in the delafloxacin group and 93.3% (14/15) in the vancomycin/aztreonam group.
A total of 63.4% of obese patients in the vancomycin/aztreonam group had at least one treatment-emergent adverse event (TEAE), compared with 54.2% in the delafloxacin group. The most common TEAEs in both study arms were nausea and diarrhea.