Recently, the FDA approved a novel flouroquinolone-class drug for the management of acute bacterial skin and soft tissue infections. Known as delafloxacin (brand name Baxdela), this broad-spectrum flouroquinolone has activity against Gram negatives, anaerobes and atypical organisms (Legionella, Mycoplasma, Chlamydia species) similar to that of other quinolones; however unlike other quinolones, this particular drug showed promising activity against Gram-positive organisms, specifically quinolone-resistant Staphylococci, including MRSA.

Data supporting the FDA approval of this drug came from two sequential phase 3 clinical trials via the PROCEED (PROve Clinical Efficacy and Effect of Delvafloxacin) study, which compared delafloxacin to combination vancomycin and aztreonam for the management of acute skin and soft tissue infections. Both trials achieved their primary endpoint of showing that delafloxacin was non-inferior to combination vancomycin/aztreonam in reducing erythema associated with skin/soft tissue infections within a 72 hour period. It also showed that this drug was well tolerated, with only a 0.9% discontinuation rate due to adverse events; interestingly, prolongation of QTc (a common side effect of quinolones) was not noticed with this particular drug, and no significant hepatic, renal or glycemic adverse events were noted either. Moreover, the oral form of the drug (450 mg tablet) achieved a similar area under the curve to the 300 mg IV dose, making both forms bioequivalent.

A subsequent study by McCurdy and colleagues used 685 Staphylococcus aureus isolates obtained from the above trials, and submitted them for susceptibility testing using CLSI guideline breakpoints. Based on analysis of these isolates, it was determined that cure rates of 96-98% were being achieved in cases where both MRSA and levofloxacin-resistant Staph aureus isolates were associated with acute soft tissue infection.

These studies all suggest the delafloxacin could prove to be a useful agent in the treatment of acute skin and soft tissue infections, providing adequate coverage for a wide variety of bacteria (including quinolone-resistant Staphylococci and MRSA) while providing less potential side effects to patients when compared to other drugs. It will be interesting to see how this drug fares with other novel soft tissue infection antibiotics, including linezolid (which can also be given in an oral form), as well as dalbavancin and oritavancin, which can be administered potentially as a one time dose. Further comparison studies of these various drugs with delafloxacin will prove useful in determining its ultimate role in the treatment of acute skin and soft tissue infections.

While there is additional active against MRSA, the drug does not appear to have significantly different spectrum from ciprofloxacin/levofloxacin for Gram negative pathogens (it does appear to be active vs Pseudomonas (unlike moxifloxacin) which is a very rare cause of skin infections. but can complicate diabetic foot infections.  As such, the likely niche for this drug, at least initially, may be as an additional oral MRSA agent and perhaps for diabetic foot infections.  In the future, this may be a usea therapy for more invasive MRSA infections (with an oral drug), however studies demonstrating efficacy in infections such as MRSA bone and joint infections or blood stream infections have not been performed as of yet.

References:

https://www.ncbi.nlm.nih.gov/pubmed/28630189

https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofv133.493/2634989/Results-of-a-Global-Phase-3-Study-of-Delafloxacin

http://melinta.com/melinta-therapeutics-lead-candidate-delafloxacin-yields-positive-top-line-results-in-phase-3-study-in-patients-with-absssi/