NEW ORLEANS, LA—Intravenous (IV) and oral delafloxacin (DLX), an investigational, full-spectrum anionic fluoroquinolone, exhibits tolerability and efficacy comparable to those for vancomycin/aztreonam (VAN/AZ) among adult patients with acute bacterial and skin structure infections (ABSSSI), according to findings from a randomized, double-blind multicenter Phase 3 study, reported at IDWeek 2016.
“In ABSSSI patients, IV/oral DLX monotherapy was non-inferior to IV VAN/AZ combination therapy for both the objective response (decrease in lesion size ≥20%) at 48–72 hours after initiation of study drug, and the investigator-assessed response rates of cure and success (cure + improved) at followup,” reported coauthor Laura Lawrence, BS, of Melinta Therapeutics, Inc. in New Haven, CT. “The addition of oral DLX appears to maintain the initial clinical response seen with IV DLX.”
The authors enrolled 850 adult patients with major abscesses, cellulitis, or wound or burn infections involving ≥75cm2 erythema and two or more systematic signs. The average age of participants was 50.7 years and the average lesion area was 353cm2. Forty-eight percent of patients had cellulitis, 25% had abscesses, and 26% had wound infections. One percent of participants had burn infections.
Study participants were randomly assigned (1:1) to receive DLX (300mg IV twice daily for 3 days) with switch to 450mg oral DLX (450mg), or VAN (IV 15mg/kg) plus AZ for between 5–14 days.
Objective response at 48–72 hours was the study’s primary endpoint.
In the intent-to-treat (ITT) population, objective response rates were 83.7% and 80.6% for DLX and VAN/AZ, respectively. Investigator-assessed cure rates at followup were 57.7% and 59.7%, respectively. Among patients who could be evaluated for eradication of methicillin-resistant Staphylococcus aureus (MRSA), DLX outcomes were similar to VAN/AZ (96% vs. 97%).
“At least 43.6% DLX and 39.3% VAN patients had at least one treatment-emergent adverse event,” Ms. Lawrence noted. “The most common DLX events were diarrhea and nausea; which were mild and did not lead to discontinuation.”
The DLX and VAN/AZ study arms had similar rates of severe adverse events (DLX: 3.8% vs. VAN/AZ: 4.0%). Adverse events leading to premature study discontinuation occurred in 2.4% of DLX group patients and 2.8% of VAN/AZ patients.
Two patient deaths (0.5%) occurred among patients in the VAN/AZ group.