title: Levofloxacin cures experimental pneumonic plague in African green monkeys.
abstract: BACKGROUND
  Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease.
  
  
  RESULTS
  Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3-145 (mean = 65) 50% lethal (LD(50)) doses of Y. pestis strain CO92. Telemetered body temperature >39 °C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a "humanized" dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53-165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions.
  
  
  CONCLUSIONS
  Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America. CLayton@MRIresearch.org
authors.forename: Robert Colby
authors.initials: RC
authors.lastname: Layton
authors.forename: William
authors.initials: W
authors.lastname: Mega
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.forename: Trevor L
authors.initials: TL
authors.lastname: Brasel
authors.forename: Edward B
authors.initials: EB
authors.lastname: Barr
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Gigliotti
authors.forename: Frederick
authors.initials: F
authors.lastname: Koster
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D064704:Levofloxacin; D008168:Lung / Q000473:pathology; D015242:Ofloxacin / Q000008:administration & dosage*; D010930:Plague / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018419:Primate Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013902:Radiography, Thoracic; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin