Delafloxacin 450mg tablets

The extensive use of fluoroquinolones has been consequently accompanied by the emergence of bacterial resistance, which triggers the necessity to discover new compounds. Delafloxacin is a brand-new anionic non-zwitterionic fluoroquinolone with some structural particularities that give it attractive proprieties: high activity under acidic conditions, greater in vitro activity against Gram-positive bacteria-even those showing resistance to currently-used fluoroquinolones-and nearly equivalent affinity for both type-II topoisomerases (i.e., DNA gyrase and topoisomerase IV). During phases II and III clinical trials, delafloxacin showed non-inferiority compared to standard-of-care therapy in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, which resulted in its approval in 2017 by the Food and Drug Administration for indications. Thanks to its overall good tolerance, its broad-spectrum in vitro activity, and its ease of use, it could represent a promising molecule for the treatment of bacterial infections.

Abstract licence: CC BY

The global spread of antibacterial-resistant strains, especially methicillin-resistant Staphylococcus aureus (MRSA) for acute bacterial skin and skin structure infections (ABSSSIs), has driven the need for novel antibacterials. Delafloxacin [Quofenix™ (EU); Baxdela® (USA)], a new fluoroquinolone (FQ), has a unique chemical structure that enhances its antibacterial activity in acidic environments such as occurs in ABSSSIs (including S. aureus infections). Delafloxacin (intravenous and oral formulations) is approved in several countries for the treatment of adults with ABSSSIs (featured indication). In intent-to-treat analyses in pivotal phase 3 trials in adults with ABSSSIs, including those with comorbid disease, intravenous delafloxacin monotherapy (± oral switch after six doses) twice daily was noninferior to intravenous vancomycin + aztreonam for primary endpoints, as specified by the FDA (objective response rate at 48–78 h after initiation of therapy) and the EMA [investigator-assessed clinical cure rate at the follow-up visit at day 14 (± 1 day)]. Delafloxacin was generally well tolerated, with most treatment-related adverse events mild to moderate in severity and few patients discontinuing treatment because of these events. Relative to vancomycin + aztreonam (a non-FQ regimen), delafloxacin treatment was not associated with an increased risk of FQ-associated AEs of special interest. Given its unique chemical structure that confers novel properties relative to other FQ and its broad spectrum of activity against common clinically relevant Gram-positive pathogens, including against MRSA strains (± FQ-resistance mutations), and Gram-negative pathogens, intravenous delafloxacin (± oral switch) provides a novel emerging option for the treatment of adult patients with ABSSSIs.

Abstract licence: CC BY-NC

Abstract: Delafloxacin (DLX) is a new fluoroquinolone pending approval, which has shown a good in vitro and in vivo activity against major pathogens associated with skin and soft tissue infections and community-acquired respiratory tract infections. DLX also shows good activity against a broad spectrum of microorganisms, including those resistant to other fluoroquinolones, as methicillin-resistant Staphylococcus aureus . Its pharmacokinetic properties and excellent activity in acidic environments make DLX an alternative in the treatment of these and other infections. In this manuscript, a detailed analysis of this new fluoroquinolone is performed, from its chemical structure to its in vivo activity in recently published clinical trials. Its possible place in the current antimicrobial outlook and in other infectious models is also discussed. Keywords: Delafloxacin, fluoroquinolones, methicillin-resistant Staphylococcus aureus , therapy

Abstract licence: CC BY-NC

Delafloxacin (Baxdela™) is a fluoroquinolone antibacterial with activity against both gram-positive and gram-negative pathogens being developed by Melinta Therapeutics. The drug is being investigated or considered as a treatment for various bacterial infections and in June 2017 received approval in the USA for the treatment of acute bacterial skin and skin structure infections. This article summarizes the milestones in the development of delafloxacin leading to this first global approval for the treatment of acute bacterial skin and skin structure infections.

Abstract licence: CC BY-NC

In this study delafloxacin resistance mechanisms in Escherichia coli strains were analyzed. Delafloxacin is a new fluoroquinolone, that is approved for clinical application however, resistance against this agent is scarcely reported. In our study 37 E. coli strains were included and antimicrobial susceptibility testing was performed for ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, imipenem. Six delafloxacin resistant E. coli strains were selected for whole-genome sequencing and all of them exhibited resistance to other fluoroquinonlones and showed an extended-spectrum beta-lactamase phenotype. The six delafloxacin resistant E. coli strains belonged to different sequence types (STs) namely, ST131 (2 strains), ST57 (2 strains), ST162 and ST15840. Each delafloxacin resistant strain possessed multiple mutations in quinolone resistance-determining regions (QRDRs). Notably, three mutations in gyrA Ser83Leu, Asp87Asn and parC Ser80Ile were in strains of ST162, ST57 and ST15840. However, the two strains of ST131 carried five combined mutations namely, gyrA Ser83Leu, Asp87Asn, parC Ser80Ile, Glu84Val, parE Ile549Leu. Association of delafloxacin resistance and production of CTX-M-15 in ST131, CMY-2 in ST162 and ST15840 was detected. In this study a new ST, ST15840 of clonal complex 69 was identified. Our results demonstrate, that at least three mutations in QRDRs are required for delafloxacin resistance in E. coli.

Abstract licence: CC BY