Efficacy of Aerosol MP-376 (Levofloxacin Inhalation Solution) in Mouse Lung Infection Models due to Pseudomonas aeruginosa.

Antimicrob Agents Chemother. 2009 Jun 15. [Epub ahead of print]

Efficacy of Aerosol MP-376 (Levofloxacin Inhalation Solution) in Mouse Lung Infection Models due to Pseudomonas aeruginosa.

Sabet M, Miller CE, Nolan TG, Senekeo-Effenberger K, Dudley MN, Griffith DC.

Mpex Pharmaceuticals, Inc., San Diego, CA.

Progressive respiratory failure due to Pseudomonas aeruginosa is the leading cause of morbidity and mortality in cystic fibrosis patients. Pulmonary delivery of anti-microbial agents provides high concentrations of drug directly at the site of infection and attains PK-PD indices exceeding those which can be achieved with systemic dosing.

MP-376 is a new formulation of levofloxacin that enables the safe aerosol delivery of high concentrations of drug to pulmonary tissues. In vivo studies were conducted to demonstrate the efficacy of MP-376 in mouse models of pulmonary infection. The superiority of aerosol dosing over systemic dosing was demonstrated in both acute and chronic lung infection models. In an acute lung infection model, treatment with single or twice daily dosing of aerosolized MP-376 reduced the lung bacterial load to a greater extent than aerosolized tobramycin or aztreonam at similar or higher doses.

The bacterial killing observed in the lung with aerosolized MP-376 in the acute pulmonary infection model translated to improved survival (p<0.05). style="font-weight: bold; color: rgb(255, 0, 0);">In a chronic pulmonary infection model, aerosolized MP-376 had superior antimicrobial effects compared to aztreonam (p<0.05)>0.05).

In summary, these data show in vivo activity of aerosol MP-376 in the treatment of acute and chronic lung infections caused by P. aeruginosa.