Delafloxacin: what does a new fluoroquinolone offer?

Abstract

Delafloxacin is a novel anionic fluoroquinolone with a different chemical structure from currently marketed fluoroquinolones, which gives it distinct physicochemical characteristics, being active in both acidic and neutral environments. Delafloxacin is also unique in showing a dual-targeted equipotent inhibition of the essential bacterial enzymes DNA gyrase and topoisomerase IV, which may explain the very low frequencies of spontaneous mutations in vitro. It shows potent in vitro activity against a broad spectrum of Gram-negative bacteria, including some fluoroquinolone-resistant strains, and increased efficiency against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, although it is always necessary to determine the in vitro activity of delafloxacin against fluoroquinolone-resistant isolates. Delafloxacin exhibits linear pharmacokinetics, a wide volume of distribution, and a concentration-dependent pattern of antimicrobial killing, a property that allows the use of high doses for greater effectiveness in some difficult-to-treat infections. Delafloxacin is available for clinical use in oral and intravenous formulations and has been approved for the treatment of acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia based on the results from phase II and III clinical trials. Overall, delafloxacin has been well tolerated and has a low profile of drug-drug interactions. Its activity in local acidic environments and biofilms could play a role in the treatment of biofilm-related infections such as osteoarticular and medical device-associated infections, and due to its broad spectrum, it can also be useful in polymicrobial infections. Delafloxacin is an interesting new addition to the therapeutic arsenal against common and difficult-to-treat infections.