EFFECTIVE TREATMENT AGAINST PNEUMONIC PLAGUE BY AEROSOLIZED GENTAMICIN

The pathogen Yersinia pestis is the causative agent of pneumonic plague. It is classified by the CDC as a potential bioweapon. Infection occurs upon inhalation of aerosols or droplets containing the pathogen. Without early antibiotic treatment within 24 hours, the disease progresses to respiratory failure, shock, and rapid death. Antimicrobial treatment regimens recommended against plague include parenteral or oral therapy with aminoglycosides, tetracyclines, and fluoroquinolones. As lungs are the primary target organ during pneumonic plague, we evaluated in the present study, the protection afforded by aerosolized gentamicin against respiratory infection with Y. pestis, using a mouse infection model.

Complete protection was achieved when the aerosolized gentamicin treatment (3mg/kg/day in the lungs, for 5 days), began 24 hours post exposure to a lethal Y. pestis intranasal challenge (10LD₅₀). Parenteral treatment with a low dose, equivalent to the inhaled dose of gentamicin failed to protect the animals, emphasizing the advantage of the aerosolized treatment that maximizes drug delivery to the infection site in the lung. The aerosolized gentamicin treatment could be delayed as long as 48 hours post challenge and still provide full protection against the lethal Y. pestis challenge.

Our results provide evidence that inhaled gentamicin treatment is highly effective against pneumonic plague, thus paving the way for evaluation of new combinational treatment modalities against plague.