Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections

Abstract

Introduction: In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram-negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach. Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin. In addition, recent data on clinical efficacy and safety from clinical trials have been included. Expert opinion: Delafloxacin represents an attractive therapeutic option due to a broad antimicrobial and favorable pharmacokinetic and pharmacodynamic profile. Several in vitro studies have demonstrated the low potential for resistance selection if used in empirical regimens. Delafloxacin is a promising candidate for the treatment of Gram-positive infections, especially if co-infection with other pathogens is suspected. This is because of the very low MIC of the agent for Gram-positive (including MRSA) and anaerobic bacteria and because of the wide spectrum of activity against Gramnegative organisms. For these interesting microbiological and PK/PD characteristics we expect future uses of this drug in other indications such as diabetic foot infection, osteomyelitis, prosthetic joint infections, abdominal infections and central nervous system infections. ARTICLE HISTORY

Development of Lipomer Nanoparticles for the Enhancement of Drug Release, Anti-Microbial Activity and Bioavailability of Delafloxacin

“…This change results in a weak acid property, and therefore, DFL usually exists in a deprotonated form at a neutral pH with a pKa value of 5.4, providing enhanced antibacterial potency in an acidic environment and reducing the minimum inhibitory concentrations (MICs). These properties also lead to increased accumulation and better distribution characteristics into infected target tissues than other marketed fluoroquinolones [6][7][8]. Moreover, the enzyme-inhibiting effects of DFL against DNA gyrase and topoisomerase IV is more balanced in comparison to other fluoroquinolones.…”

“…Therefore, DFL exhibits very low frequencies of spontaneous mutation in vitro as an equipotent enzyme inhibition limit resistance [9,10]. DFL possesses potent and broad-spectrum antibiotic activities against both Gram-positive and negative aerobic and anaerobic bacteria, including bactericidal effects against methicillin-resistant Staphylococcus aureus (MRSA) [6].…”

New Bugs and New Drugs: Updates in Clinical Microbiology

“…The global emergence and spread of extensively resistant bacteria is a high-priority concern. However, it is encouraging that, in recent years, a number of new anti-infective agents with activity against multidrug-resistant bacteria have been approved for clinical use (69,71,72,78,81,(85)(86)(87)(88)90).…”

“…Delafloxacin (trade name, Baxdela ® ) is a fluoroquinolone antibiotic that has broad-spectrum activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus; gramnegative bacteria; atypical organisms, including Mycoplasma species, Chlamydophila pneumoniae, and Legionella; and anaerobic bacteria (85)(86)(87)(88).…”

“…The FDA-approved indication for use of delafloxacin is acute bacterial skin and skin structure infections using oral and intravenous formulations (86,89). Currently there are FDA MIC and disk diffusion breakpoints for S. aureus (methicillin resistant and methicillin susceptible), Staphylococcus haemolyticus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, Enterococcus faecalis, Enterobacteriaceae, and P. aeruginosa (89).…”