Delafloxacin (Baxdela) for Acute Bacterial Skin Infections

December 6, 2017

Delafloxacin (Baxdela) for treatment of acute bacterial skin and skin structure infections including cellulitis, wound infection, major cutaneous abscess, and burn infection.

The FDA has approved delafloxacin (Baxdela) from Melinta for treatment of acute bacterial skin and skin structure infections (ABSSSI).

Delafloxacin is a fluoroquinolone antibiotic that inhibits DNA gyrase and topoisomerase IV enzymes. The spectrum of activity of delafloxacin includes gram positive and negative organisms, including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Efficacy

The efficacy of delafloxacin was shown in two phase III trials with patients with ABSSSIs including cellulitis, wound infection, major cutaneous abscess, and burn infection. In both, patients were randomized to receive either delafloxacin or vancomycin 15 mg/kg/dose plus aztreonam for 5 to 14 days. A patient was considered a responder if there was >20% reduction in the lesion erythema area compared to baseline at 48 to 72 hours after treatment initiation. In both trials, delafloxacin was proven to be non-inferior to vancomycin plus aztreonam.1

In the first trial, patients were randomized to receive delafloxacin 300 mg IV every 12 hours or vancomycin 15 mg/kg/dose plus aztreonam. In the delafloxacin arm, 78.2% of patients were responders, compared to 80.9% in the vancomycin plus aztreonam arm. In the second trial, patients were randomized to receive delafloxacin 300 mg IV every 12 hours for 6 doses, then delafloxacin 450 mg oral tablet every 12 hours for a minimum of 10 and up to a maximum of 28 doses total or vancomycin 15 mg/kg/dose plus aztreonam. In the delafloxacin arm, 83.7% of patients were responders, compared to 80.6% in the vancomycin plus aztreonam arm.2,3

Safety

The most common adverse reactions with delafloxacin include nausea, diarrhea, headache, transaminase elevations, and vomiting. Adverse effects are consistent with other fluoroquinolones including tendinitis, tendon rupture, peripheral neuropathy, central nervous system effects, and exacerbation of myasthenia gravis. It is recommended that use be avoided in patients with myasthenia gravis.

Safety and efficacy in patients  under age 18  have not been established for delafloxacin. Geriatric patients are at increased risk for severe tendon disorders, including rupture. The risk for tendon disorders is increased in patients receiving concomitant corticosteroid therapy.

Limited data is available on the any increased risk of major birth defects or miscarriage with delafloxacin in pregnant women. No data is readily available on the presence of delafloxacin in human milk; however, it is excreted in breast milk in animal models.

Dosing

The recommended dosing of delafloxacin is 300 mg IV over 60 min every 12 hours, or 450 mg tablet every 12 hours for 5 to 14 days. It should be administered at least 2 hours before or 6 hours after antacids containing magnesium, aluminum with sucralfate, metal cations such as iron, multivitamins containing zinc or iron, or didanosine-buffered tablets for oral suspension.

There are no renal dose adjustments for oral delafloxacin, but use is not recommended for patients with estimated glomerular filtration rate (eGFR) <15. The IV formulation adjustments for eGFR between 15 and 29  is 200 mg every 12 hours or 200 mg every 12 hours, and then switch to 450 mg oral tablet every 12 hours.

References

1. Delafloxacin [package insert] Lincolnshire, IL: Melinta Therapeutics, Inc.; 2017

2. Cammarata, S., Gardovskis, J., Farley, B., et.al. Results of a global phase 3 study of delafloxacin (dlx) compared to vancomycin with aztreonam (VAN) in acute bacterial skin and skin structure infections (ABSSSI). Open Forum Infectious Dis. Dec. 2015. 2;1;776.

3. ClinicalTrials.gov [Internet]. 2013 November 15. Identifier NCT01984684, Delafloxacin vs Vancomycin and Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections. Available at: https://clinicaltrials.gov/ct2/show/results/NCT01984684.