Delafloxacin 300mg powder for solution for infusion vials

AbstractBackgroundDelafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This network meta-analysis (NMA) was conducted to evaluate the relative efficacy of delafloxacin versus other comparators used for managing patients with ABSSSI.MethodsA systematic literature review was conducted to identify randomised controlled trials (RCTs) evaluating adults (≥ 18 years) with ABSSSI, complicated SSSI (cSSSI), complicated skin and soft tissue infections (cSSTI) or severe cellulitis with pathogen of gram-positive, gram-negative, or mixed aetiology. OVID MEDLINE®, Embase, Epub Ahead of Print, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception through 12 April 2019. A feasibility assessment was conducted, followed by an NMA, which was run in a Bayesian framework. The interventions included in the NMA encompassed monotherapy or combination therapies of amoxicillin/clavulanate, ampicillin/sulbactam, ceftaroline, ceftobiprole, dalbavancin, daptomycin, delafloxacin, fusidic acid, iclaprim, linezolid, omadacycline, oxacillin + dicloxacillin, standard therapy, tedizolid, telavancin, tigecycline, vancomycin, vancomycin + aztreonam and vancomycin + linezolid.ResultsA feasibility assessment was performed and evidence networks were established for composite clinical response (n = 34 studies), early clinical response (n = 16 studies) and microbiological response (n = 14 studies) in the overall study population, composite clinical response (n = 4 studies) in obese subpopulation and for composite clinical response (n = 18 studies) and microbiological response (n = 14 studies) in patients with methicillin-resistantStaphylococcus aureus(MRSA) infection. Delafloxacin performed significantly better than fusidic acid, iclaprim, vancomycin, and ceftobiprole for composite clinical response. Delafloxacin was comparable to dalbavancin, daptomycin, fusidic acid, iclaprim, linezolid, omadacycline, tedizolid, vancomycin, vancomycin + aztreonam and vancomycin + linezolid in the analysis of early clinical response, whereas for microbiological response, delafloxacin was comparable to all interventions. In the obese subpopulation, the results favoured delafloxacin in comparison to vancomycin, whilst the results were comparable with other interventions among the MRSA subpopulation.ConclusionsDelafloxacin is a promising new antibiotic for ABSSSI demonstrating greater improvement (composite clinical response) compared to ceftobiprole, fusidic acid, iclaprim, telavancin and vancomycin and comparable effectiveness versus standard of care for all outcomes considered in the study.

Abstract licence: CC BY 4.0

Background: This study aims to assess the clinical efficacy and adverse events of delafloxacin for the treatment of acute bacterial infections in adult patients through meta-analysis.Methods: The PubMed, Embase, Cochrane library, Web of Science, and Clinical trails databases were searched up to 26 March 2022. Only randomized controlled trials (RCTs) that evaluated delafloxacin and comparator antibiotics for treating acute bacterial infections in adult patients were included. The clinical cure rate and microbiological eradication rate at the posttreatment evaluation, while the secondary outcomes included the risk of adverse events (AEs).Results: In total, six randomized controlled trials (RCTs) involving 3,019 patients with acute bacterial infection were included. There were no significant differences in the clinical cure rate between delafloxacin and comparators (OR = 1.06%, 95% CI = 0.89–1.26, I2 = 0%). Overall, the results showed that delafloxacin had a microbiological eradication rate (documented and presumed) similar to the comparators (OR = 1.33%, 95% CI = 0.94–1.88, I2 = 0%) in the pooled analysis of the six studies. Any treatment-emergent adverse events (TEAEs) did not show significant differences between delafloxacin and the comparators (OR = 0.93%, 95% CI = 0.80–1.08, I2 = 75%). Serious adverse events (SAEs) did not differ between the delafloxacin and comparators (OR = 0.94%, 95% CI = 0.67–1.32, I2 = 0%). The results of gastrointestinal disorders were (OR = 1.26%, 95% CI = 1.01–1.56, I2 = 89%), and nausea, vomiting, and diarrhea were (OR = 0.77%, 95% CI = 0.45–1.34, I2 = 79%), (OR = 1.00%, 95% CI = 0.74–1.36, I2 = 72%), and (OR = 2.10%, 95% CI = 1.70–2.96, I2 = 0%), respectively. The results showed that there was no significant difference in the incidence of nausea and vomiting between delafloxacin and the comparator, but the incidence of diarrhea was higher. The analysis of neurological disorders indicated that the incidence of nervous system disorders was lower in the delafloxacin group (OR = 0.71%, 95% CI = 0.50–1.01, I2 = 52%).Conclusion: The clinical efficacy, microbiological eradication rate and the incidence of AEs of delafloxacin in the treatment of acute bacterial infections were similar to those of the comparators, as an alternative therapeutic agent.

Abstract licence: CC BY 4.0

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.

Abstract licence: CC BY 4.0

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 4.0