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Post-exposure prophylaxis of systemic anthrax in mice and treatment with fluoroquinolones
J Steward1, M S Lever, A J H Simpson
1Biomedical Sciences, Dstl Porton Down, Salisbury, Wiltshire SP4 OJQ, UK. jasteward@dstl.gov.uk
Objectives:
To compare the fluoroquinolones gatifloxacin and moxifloxacin with ciprofloxacin for post-exposure prophylaxis of systemic anthrax in a BALB/c mouse model.
Methods:
Treated mice and controls were inoculated subcutaneously with 5 x 10(4) spores/mouse of Bacillus anthracis Ames strain and observed for 37 days after challenge. Treated mice were given 100 mg/kg of antibiotic orally twice daily for 14 days, starting at various times post-challenge.
Results:
Treatment starting 6 h post-challenge resulted in survival rates of 90%, 15% and 40% for gatifloxacin, moxifloxacin and ciprofloxacin, respectively. Treatment commencing 24 h post-challenge resulted in survival rates of 65%, 10% and 5%, respectively. Treatment starting more than 24 h after exposure had little effect on survival.
Conclusions:
Gatifloxacin appeared to be more effective than moxifloxacin or ciprofloxacin, at similar doses, for early post-exposure treatment of murine systemic anthrax. However, these results might be due to differences in potency or pharmacokinetic properties.
Insights
Gatifloxacin demonstrated superior efficacy compared to moxifloxacin and ciprofloxacin for early post-exposure anthrax treatment in mice. Prompt treatment is crucial for effective prophylaxis against systemic anthrax.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Systemic anthrax poses a significant bioterrorism threat.
- Fluoroquinolones are a class of antibiotics used for anthrax prophylaxis.
- Comparative efficacy data for newer fluoroquinolones in anthrax treatment is limited.
Purpose of the Study:
- To evaluate gatifloxacin and moxifloxacin against ciprofloxacin for post-exposure anthrax prophylaxis.
- To assess the impact of treatment timing on survival rates.
Main Methods:
- BALB/c mice were challenged with Bacillus anthracis Ames strain.
- Antibiotics (gatifloxacin, moxifloxacin, ciprofloxacin) were administered orally at 100 mg/kg twice daily for 14 days.
- Treatment initiation varied from 6 to 24 hours post-challenge.
Main Results:
- Gatifloxacin showed the highest survival rates (90% at 6h, 65% at 24h).
- Moxifloxacin and ciprofloxacin demonstrated significantly lower survival rates.
- Treatment initiated >24 hours post-exposure had minimal impact on survival.
Conclusions:
- Gatifloxacin appears more effective than moxifloxacin or ciprofloxacin for early anthrax treatment in mice.
- Efficacy may be influenced by drug potency and pharmacokinetic properties.
- Timely administration of antibiotics is critical for successful anthrax prophylaxis.
