Plazomicin is effective in a non-human primate pneumonic plague model
William M Mega1, Melanie Doyle-Eisele1, Robert T Cass2
1Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, United States.
Abstract:
The efficacy of plazomicin for pneumonic plague was evaluated in a non-human primate model. African Green monkeys challenged with a lethal aerosol of Yersinia pestis [median (range) of 98 (15-331) LD50s] received placebo (n=12) or 'humanized' dose regimens (6.25, 12.5 or 25mg/kg every 24h) of plazomicin (n=52) after the onset of fever for a duration of 5 or 10days. All animals treated with placebo died, while 36 plazomicin-treated animals survived through study end. The majority (33/36) were either in the 10-day (high-/mid-/low-dose) or 5-day high-dose groups. The findings suggest an exposure range of plazomicin for treatment of pneumonic/bacteremic Y. pestis infection in humans.
Insights
Plazomicin demonstrated efficacy in treating pneumonic plague in a non-human primate model. Survival rates were significantly higher in animals treated with plazomicin compared to placebo, suggesting its potential for human use.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Pneumonic plague, caused by Yersinia pestis, is a severe and often fatal infection.
- Limited treatment options exist, necessitating the evaluation of novel antimicrobial agents.
Purpose of the Study:
- To evaluate the efficacy of plazomicin in a non-human primate model of pneumonic plague.
- To determine optimal dosing and duration for plazomicin treatment against Yersinia pestis infection.
Main Methods:
- African Green monkeys were challenged with a lethal aerosol of Yersinia pestis.
- Animals received placebo or varying doses of plazomicin (6.25, 12.5, 25 mg/kg every 24h) for 5 or 10 days post-fever onset.
- Survival rates and clinical outcomes were monitored.
Main Results:
- All placebo-treated animals succumbed to infection.
- 36 out of 52 plazomicin-treated animals survived the study.
- Higher survival rates were observed in animals receiving 10-day or high-dose 5-day plazomicin regimens.
Conclusions:
- Plazomicin exhibits significant efficacy against pneumonic plague in a relevant animal model.
- The study suggests potential therapeutic exposure ranges for plazomicin in treating human Yersinia pestis infections.
- Further clinical investigation is warranted to confirm plazomicin's utility in human plague cases.
