Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties

Sarah C. J. Jorgensen, Nicholas J. Mercuro, Susan L. Davis, Michael J. Rybak

Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.