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

Abstract

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.

Emerging antibiotics for community-acquired pneumonia

“…It also has greater affinity for DNA gyrase that older fluoroquinolones [83], which contributes to it having MICs that are consistently three-to five-fold lower. These features mean that delafloxacin not only exhibits a broader spectrum of activity but also confers less resistance compared to other fluoroquinolones.…”

In vitro Susceptibilities of Methicillin-Susceptible and Resistant Staphylococci to Traditional Antibiotics Compared to a Novel Fluoroquinolone

“…In vivo pharmacokinetic and pharmacodynamic studies have demonstrated rapid oral absorption of delafloxacin, high bioavailability (60-70%), and renal excretion [19]. Delafloxacin is a concentration-dependent fluoroquinolone, exhibiting in vivo MICs of ≤ 1 mg/L against P. aeruginosa and 0.25 mg/L for Klebsiella pneumoniae, which predicts , minimum inhibitory concentration at which growth of 90% of organisms is inhibited, expressed in micrograms per milliliter (μg/ml), which were only calculated for microbes with more than 10 isolates efficacy against 75% and 78% of strains respectively [19][20][21].…”

“…In vitro studies have shown MIC levels for delafloxacin to be 3-5 times lower than other fluoroquinolones against Gram-positive microbes [21]. Additionally, multiple groups have shown its higher in vitro efficacy against Gram-positive organisms compared to other in-class agents [22,23].…”

Evaluation of Eravacycline: A Novel Fluorocycline

“…Currently, some available agents used to treat these MDR infections have limitations in their efficacy, spectra of activity, and side effect profile . Fortunately, the past years have produced several agents in the pipeline with novel moieties and a potential to overcome these obstacles …”

“…6,7 Fortunately, the past years have produced several agents in the pipeline with novel moieties and a potential to overcome these obstacles. [8][9][10][11] Historically, tetracyclines (TET) have been used for the management of gram-negative skin and soft tissue and intraabdominal infections (IAI). 12 Although their use had been challenged with the onset of bacterial resistance, the development of new TET-like antibiotics, such as omadacycline and eravacycline (ERV), have the potential to overcome these challenges.…”