Efficacy of delafloxacin against the biothreat pathogen Bacillus anthracis. (4th February 2023)

• Record Type: Journal Article
• Authors: McCurdy, Sandra; Halasohoris, Stephanie A; Babyak, Ashley L; Lembirik, Sanae; Hoover, Randall; Hickman, Mark; Scarff, Jennifer; Klimko, Christopher P; Cote, Christopher K; Meinig, J Matthew
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 78:Number 3(2023)
• Page Start: 810
• Page End: 816
• Publication Date: 2023-02-04
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkad015
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: To evaluate the in vitro activity and in vivo efficacy of delafloxacin against Bacillus anthracis, the causative agent of anthrax. Methods: MICs were obtained according to CLSI guidelines for 30 virulent isolates and 14 attenuated antibiotic-resistant strains. For the in vivo efficacy study, mice were administered delafloxacin (30–62.5 mg/kg) subcutaneously, or ciprofloxacin (30 mg/kg) intraperitoneally beginning at either 24 or 48 ± 1 h post-challenge (post-exposure prophylaxis) and continued every 12 h for 14 days with study termination on day 30. The mean inhaled dose in the study was approximately 103 × LD50 equivalents, and the range was 87–120 × LD50 . Results: Delafloxacin (MIC90 = 0.004 mg/L) was 16-fold more potent than ciprofloxacin (MIC90 = 0.06 mg/L) against a 30-strain set of virulent B. anthracis . Against a panel of attenuated antibiotic-resistant strains, delafloxacin demonstrated potency ≥128-fold over that observed with ciprofloxacin. When evaluated in vivo, mice treated with all delafloxacin doses tested at 24 h post-challenge demonstrated equivalent survival compared with mice treated with the positive control ciprofloxacin. Because of the high challenge dose of spores, mice treated at 48 h showed rapid and high mortality in all groups including the positive control. Surviving animals in all delafloxacin- and ciprofloxacin-treated groups (24 and 48 h) showed complete splenic clearance of infection and <2.2 × 10 3 cfu/g lung tissue. Conclusions: Given the high bar set by the 100 × LD50 challenge dose in this study, the results from delafloxacin treatment are promising for the treatment of inhaled anthrax.