Delafloxacin Non-Inferior to Vancomycin/Aztreonam for ABSSSI in Pooled Phase 3 Analysis


Delafloxacin was comparable to vancomycin/aztreonam in eliminating MRSA at 98.1% versus 98.0%, respectively, at follow-up in 2 pooled phase 3 studies.

Acute bacterial skin and skin structure infections (ABSSSIs) are 1 of the most common bacterial infections, accounting for approximately 6.3 million physician visits per year. The cost of treating ABSSSIs can be substantial, particularly among patients who are hospitalized.

Delafloxacin (Baxdela), manufactured by Melinta Therapeutics, was approved by the US Food and Drug Administration (FDA) in 2017 as a new fluoroquinolone to treat ABSSSIs. The drug is an oral or intravenous antibiotic that is indicated for both gram-positive, including methicillin-resistant Staphylococcus aureus (MRSA), and gram-negative organisms.

In a new analysis published in the journal Clinical Infectious Diseases, a team of investigators report on pooled phase 3 efficacy data for delafloxacin in treating ABSSSIs. The analysis includes the results of 2 multicenter, randomized, double-blind trials called PROve Clinical Efficacy and Effect of Delafloxacin (PROCEED), comparing monotherapy delafloxacin with the combination therapy vancomycin/aztreonam.

“Delafloxacin targets both DNA gyrase and topoisomerase through intravenous (IV) administration, but is chemically distinct from other quinolones in size, shape, and its anionic versus zwitterionic charge profile,” the investigators write in the report. “These differences result in an agent with enhanced potency, particularly against gram-positive pathogens.”

The studies enrolled a total of 1510 adult patients who had been diagnosed with ABSSSI. At the point of enrollment, participants were required to have a minimum ABSSSI lesion of 75 cm2 and at least 2 systemic manifestations of infection. Prior antibiotic use was limited to 25%, as specified in the 2013 FDA guidelines.

Participants with a weight greater than 309 pounds or with severe renal impairment were excluded from 1 of the studies, Study 302, while the other study, Study 303, permitted participants weighing up to 441 pounds. A total of 44% of participants were obese across the pooled analysis.

The participants were randomized upon enrollment to the study. Subjects in the vancomycin arm received 15 mg/kg, along with 1-2 grams of aztreonam every 12 hours. For participants in the delafloxacin arm, the drug was dosed at 300 mg IV every 12 hours in Study 302, and at 300 mg IV every 12 hours for 3 days with a mandatory blinded switch to delafloxacin at 450 mg orally very 12 hours in study 303.

The primary endpoint of the trials was objective response, which was defined as >20% reduction of lesion spread of erythema area at the primary infection site at 48 to 72 hours (+ 2 hours), in the absence of clinical failure. Secondary endpoints included investigator-assessed response based on the resolution of signs and symptoms at follow-up (Day 14 + 1) and late follow-up (Day 21-28).

The pooled study results indicate that in the intent-to-treat analysis set, the objective response was 81.3% in the delafloxacin arm and 80.7% in the comparator arm (mean treatment difference 0.8%, 95% confidence interval: -3.2% to 4.7). In the defined subgroups, results for objective response demonstrated that delafloxacin was comparable to vancomycin/aztreonam. The investigator-assessed success was similar between treatment arms at follow-up (84.7% vs 84.1%) and late follow-up (82.0% vs 81.7%).

Overall, delafloxacin was comparable to vancomycin/aztreonam in eliminating MRSA at 98.1% versus 98.0%, respectively, at follow-up, with the frequencies of treatment-emergent adverse events between the groups reported to be similar.

The analysis reports that IV/oral delafloxacin monotherapy was non-inferior to the combination therapy of IV vancomycin/aztreonam. Additionally, the delafloxacin regimen was well-tolerated in both studies, as well as in the pooled analysis.

“Delafloxacin possesses gram-positive/MRSA and gram-negative activity, thus providing coverage for the most important ABSSSI pathogens,” the investigators concluded. “It offers the flexibility of fixed-dose IV and oral treatment of ABSSSI, and does not require therapeutic drug monitoring. These features, in concert with its favorable safety profile, support delafloxacin as an option in the ABSSSI armamentarium.”

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