The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Bacillus anthracis Infection in BALB/c Mice and Cynomolgus Macaques

Antimicrob Agents Chemother. 2017 Sep 22;61(10):e01103-17. doi: 10.1128/AAC.01103-17. Print 2017 Oct.


The fluorocycline TP-271 was evaluated in mouse and nonhuman primate (NHP) models of inhalational anthrax. BALB/c mice were exposed by nose-only aerosol to Bacillus anthracis Ames spores at a level of 18 to 88 lethal doses sufficient to kill 50% of exposed individuals (LD50). When 21 days of once-daily dosing was initiated at 24 h postchallenge (the postexposure prophylaxis [PEP] study), the rates of survival for the groups treated with TP-271 at 3, 6, 12, and 18 mg/kg of body weight were 90%, 95%, 95%, and 84%, respectively. When 21 days of dosing was initiated at 48 h postchallenge (the treatment [Tx] study), the rates of survival for the groups treated with TP-271 at 6, 12, and 18 mg/kg TP-271 were 100%, 91%, and 81%, respectively. No deaths of TP-271-treated mice occurred during the 39-day posttreatment observation period. In the NHP model, cynomolgus macaques received an average dose of 197 LD50 of B. anthracis Ames spore equivalents using a head-only inhalation exposure chamber, and once-daily treatment of 1 mg/kg TP-271 lasting for 14 or 21 days was initiated within 3 h of detection of protective antigen (PA) in the blood. No (0/8) animals in the vehicle control-treated group survived, whereas all 8 infected macaques treated for 21 days and 4 of 6 macaques in the 14-day treatment group survived to the end of the study (56 days postchallenge). All survivors developed toxin-neutralizing and anti-PA IgG antibodies, indicating an immunologic response. On the basis of the results obtained with the mouse and NHP models, TP-271 shows promise as a countermeasure for the treatment of inhalational anthrax.

Keywords: Bacillus anthracis; TP-271; anthrax; fluorocycline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthrax / drug therapy*
  • Anthrax / microbiology
  • Anthrax / mortality
  • Anti-Bacterial Agents / therapeutic use*
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antigens, Bacterial / immunology
  • Bacillus anthracis / drug effects*
  • Bacillus anthracis / immunology
  • Bacterial Toxins / immunology
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Macaca fascicularis
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Post-Exposure Prophylaxis / methods
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology
  • Respiratory Tract Infections / mortality
  • Spores, Bacterial
  • Survival Rate
  • Tetracyclines / pharmacokinetics
  • Tetracyclines / therapeutic use*


  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Bacterial Toxins
  • Immunoglobulin G
  • Tetracyclines
  • anthrax toxin
  • TP-271

Supplementary concepts

  • Inhalation anthrax