Delafloxacin Tablets (Baxdela)
August 15, 2017 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a new fluoroquinolone for the treatment of skin and skin structure infections. Delafloxacin is a broad-spectrum agent with activity against gram-positive and gram-negative organisms. The FDA granted delafloxacin priority review because of the drug’s designation as a Qualified Infectious Disease Product. It is marketed as Baxdela.
INDICATIONS
Delafloxacin is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible organisms.1 Gram-positive organisms include Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, the Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, and Enterococcus faecalis. Gram-negative organisms include Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
DOSAGE
The recommended dose is one tablet (450 mg) orally or 300 mg by IV infusion every 12 hours for five to 14 days. Clinicians can switch patients from a 300 mg IV dose to a 450 mg oral dose to complete the treatment course. The tablets may be taken without regard to meals. Delafloxacin is available as 300 mg in a single dose vial and 450 mg tablets.
POTENTIAL ADVANTAGES
The physicochemical properties of delafloxacin enhances its ability to penetrate bacterial cells and enhance activity in acidic pH, such as cutaneous infections.2 Delafloxacin offers IV and oral dosing flexibility with interchangeability of the two dosage forms.
POTENTIAL DISADVANTAGES
Delafloxacin carries the fluoroquinolone class box warning for tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects, and exacerbation of muscle weakness in patients with myasthenia gravis.1 The most frequent adverse reactions are nausea (8%) and diarrhea (8%).
COMMENTS
The safety and efficacy of delafloxacin were evaluated in two double-blind, double-dummy, noninferiority studies in subjects with ABSSSI.1 This condition includes cellulitis, wound infections, burn infections, and major cutaneous abscesses. The overall mean surface area of the infected lesion was 307 cm2 to 353 cm2. In study 1, subjects were randomized to delafloxacin 300 mg via IV infusion every 12 hours (n = 331) or vancomycin (15 mg/kg) and aztreonam (n = 329). In study 2, subjects received six doses of IV delafloxacin and were then switched to oral 450 mg (n = 423) or vancomycin/aztreonam (n = 427). Clinical response was defined as a ≥ 20% decrease in lesion size at 48-72 hours. Investigator assessment of treatment success also was made at follow-up day 14. Success was defined as “cure + improved,” whereby subjects had complete or near resolution of signs and symptoms with no further antibacterial needed.
Response rates at 48-72 hours were 78.2% for delafloxacin, compared to 80.9% for vancomycin/aztreonam in study 1, and 83.7% and 80.6%, respectively, for study 2. Success rates at follow-up were 81.6% for delafloxacin and 83.3% for vancomycin/aztreonam in study 1, and 87.2% compared to 84.8%, respectively, for study 2. These met the FDA criteria for noninferiority (10% margin).3 The most common baseline pathogen was S. aureus (319 isolates) with MRSA, representing 144 isolates. Clinical response and success at follow-up were similar for delafloxacin and comparator vancomycin for these organisms.
CLINICAL IMPLICATIONS
The FDA defines the disease manifestation of ABSSSI as cellulitis/erysipelas, wound infections, and major cutaneous abscesses.4 It does not include less serious conditions such as impetigo or more complicated conditions such as chronic wound infections. The most common pathogens are S. pyogenes and S. aureus including MRSA. This classification does not exactly correspond to practice guidelines developed by the Infectious Diseases Society of America (IDSA), which divided skin and skin structure infections into non-purulent and purulent, with cellulitis and erysipelas falling in the former, and abscesses falling in the latter.4,5 For severe purulent infections, the IDSA lists vancomycin, linezolid, tigecycline, daptomycin, ceftaroline, and telavancin as drugs of choice. Two single-dose IV glycopeptide regimens (dalbavancin and oritavancin) have been approved since the guidelines were published. In the two clinical trials, delafloxacin was found to be noninferior to vancomycin, thus, providing another therapeutic option. Because of the limited clinical experience and the availability of numerous options, the role for delafloxacin remains to be determined. Delafloxacin is under evaluation in comparison to moxifloxacin in community-acquired pneumonia.6 The cost for delafloxacin was not available at the time of this review.
REFERENCES
- Baxdela Prescribing Information. Melinta Therapeutics. June 2017.
- Van Bambeke F. Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones. Ann Med 2014;46:512-529.
- U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for Industry. Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. Available at: http://bit.ly/2tDArfU. Accessed July 24, 2017.
- Russo A, Concia E, Cristini F, et al. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections. Clin Microbiol Infect 2016;22(Suppl 2):S27-36. doi: 10.1016/S1198-743X(16)30095-7.
- Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:147-159.
- ClinicalTrials.gov. Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults With Community-acquired Bacterial Pneumonia (DEFINE-CABP). Available at: http://bit.ly/2tucrI2. Accessed July 24, 2017.
Delafloxacin is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible organisms.
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