Levofloxacin cures experimental pneumonic plague in African Green monkeys

Robert Colby Layton, William Mega, Jacob D. McDonald, Trevor L. Brasel, Edward B. Barr, Andrew P. Gigliotti, Frederick Koster

Research output: Chapter in Book/Report/Conference proceedingChapter

18 Citations (Scopus)

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.Methods and Results:Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3-145 (mean = 65) 50% lethal (LD50) 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.Conclusion: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.

Original languageEnglish (US)
Title of host publicationPLoS Neglected Tropical Diseases
Volume5
Edition2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Cercopithecus aethiops
Levofloxacin
Plague
Aerosols
Yersinia pestis
Fever
Lethal Dose 50
Bacteremia
Primates
Bioterrorism
Tachypnea
Leukocytosis
Therapeutics
Body Temperature
Intravenous Infusions
Inhalation
Pneumonia
Head
Observation
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Layton, R. C., Mega, W., McDonald, J. D., Brasel, T. L., Barr, E. B., Gigliotti, A. P., & Koster, F. (2011). Levofloxacin cures experimental pneumonic plague in African Green monkeys. In PLoS Neglected Tropical Diseases (2 ed., Vol. 5). [e959] https://doi.org/10.1371/journal.pntd.0000959

Levofloxacin cures experimental pneumonic plague in African Green monkeys. / Layton, Robert Colby; Mega, William; McDonald, Jacob D.; Brasel, Trevor L.; Barr, Edward B.; Gigliotti, Andrew P.; Koster, Frederick.

PLoS Neglected Tropical Diseases. Vol. 5 2. ed. 2011. e959.

Research output: Chapter in Book/Report/Conference proceedingChapter

Layton, RC, Mega, W, McDonald, JD, Brasel, TL, Barr, EB, Gigliotti, AP & Koster, F 2011, Levofloxacin cures experimental pneumonic plague in African Green monkeys. in PLoS Neglected Tropical Diseases. 2 edn, vol. 5, e959. https://doi.org/10.1371/journal.pntd.0000959
Layton RC, Mega W, McDonald JD, Brasel TL, Barr EB, Gigliotti AP et al. Levofloxacin cures experimental pneumonic plague in African Green monkeys. In PLoS Neglected Tropical Diseases. 2 ed. Vol. 5. 2011. e959 https://doi.org/10.1371/journal.pntd.0000959
Layton, Robert Colby ; Mega, William ; McDonald, Jacob D. ; Brasel, Trevor L. ; Barr, Edward B. ; Gigliotti, Andrew P. ; Koster, Frederick. / Levofloxacin cures experimental pneumonic plague in African Green monkeys. PLoS Neglected Tropical Diseases. Vol. 5 2. ed. 2011.
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