Post-exposure therapy of inhalational anthrax in the common marmoset

Int J Antimicrob Agents. 2011 Jul;38(1):60-4. doi: 10.1016/j.ijantimicag.2011.03.003. Epub 2011 May 6.

Abstract

The aim of this study was to compare the pharmacokinetics and efficacy of ciprofloxacin as post-exposure therapy against inhalational anthrax in the common marmoset (Callithrix jacchus) with other non-human primate models in order to determine whether the marmoset is a suitable model to test post-exposure therapies for anthrax. Pharmacokinetic (PK) and efficacy studies with ciprofloxacin were performed in the marmoset. Ciprofloxacin plasma pharmacokinetics were determined in six animals in separate single-dose and multiple-dose studies and were analysed by high-performance liquid chromatography (HPLC). A separate group of marmosets was exposed to ca. 100× the 50% lethal dose (LD(50)) of Bacillus anthracis Ames strain by the airborne route. On Day 5 of a twice-daily dosing regimen of 17.5 mg/kg, the ciprofloxacin half-life (t(1/2)), maximum drug concentration (C(max)) and area under the concentration-time curve (AUC) in marmoset plasma were 1.9 h, 2.1 μg/mL and 7.9 μg/mL/h, respectively. Naïve untreated control animals succumbed to infection by Day 9. All animals treated with ciprofloxacin, started on the day of exposure and continued for 10 days, remained healthy during the treatment period. Two antibiotic-treated animals (33%) died after withdrawal of antibiotic therapy, attributed to the germination of residual spores. In conclusion, in many respects the marmoset appears to respond to B. anthracis in a similar way to the macaque, suggesting that this small non-human primate is an acceptable, practical alternative model for the evaluation of medical countermeasures against respiratory anthrax infection.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anthrax / drug therapy*
  • Anthrax / microbiology
  • Anthrax / mortality
  • Anthrax / pathology
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacillus anthracis / drug effects
  • Bacillus anthracis / pathogenicity
  • Callithrix*
  • Ciprofloxacin / pharmacokinetics
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / therapeutic use*
  • Disease Models, Animal*
  • Female
  • Humans
  • Inhalation Exposure*
  • Male
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology
  • Respiratory Tract Infections / mortality
  • Respiratory Tract Infections / pathology
  • Spores, Bacterial / drug effects

Substances

  • Anti-Bacterial Agents
  • Ciprofloxacin