Efficacy of delafloxacin against the biothreat pathogen Bacillus anthracis.
J Antimicrob Chemother
; 78(3): 810-816, 2023 03 02.
Article
em En
| MEDLINE
| ID: mdl-36738250
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 48â±â1 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 (MIC90â=â0.004 mg/L) was 16-fold more potent than ciprofloxacin (MIC90â=â0.06 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 <2.2â×â103 cfu/g lung tissue.CONCLUSIONS:
Given the high bar set by the 100â×âLD50 challenge dose in this study, the results from delafloxacin treatment are promising for the treatment of inhaled anthrax.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bacillus anthracis
/
Antraz
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos