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Antimicrobial Agents and Chemotherapy, September 2009, p. 3923-3928, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00268-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Efficacy of Aerosol MP-376, a Levofloxacin Inhalation Solution, in Models of Mouse Lung Infection Due to Pseudomonas aeruginosa{triangledown}

Mojgan Sabet,* Courtney E. Miller, Thomas G. Nolan, Kathy Senekeo-Effenberger, Michael N. Dudley, and David C. Griffith

Mpex Pharmaceuticals, Inc., San Diego, California

Received 26 February 2009/ Returned for modification 5 April 2009/ Accepted 6 June 2009

Progressive respiratory failure due to Pseudomonas aeruginosa is the leading cause of morbidity and mortality in patients with cystic fibrosis. The pulmonary delivery of antimicrobial agents provides high concentrations of drug directly to the site of infection and attains pharmacokinetic-pharmacodynamic 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 models of mouse pulmonary infection. The superiority of aerosol dosing over systemic dosing was demonstrated in models of both acute and chronic lung infection. In a model of acute lung infection, aerosol treatment with MP-376 once or twice daily reduced the lung bacterial load to a greater extent than aerosol tobramycin or aztreonam did when they were administered at similar or higher doses. The bacterial killing by aerosol MP-376 observed in the lung in the model of acute pulmonary infection translated to improved survival (P < 0.05). In a model of chronic pulmonary infection, aerosol MP-376 had antimicrobial effects superior to those of aztreonam (P < 0.05) and effects similar to those of tobramycin (P > 0.05). In summary, these data show that aerosol MP-376 has in vivo activity when it is used to treat acute and chronic lung infections caused by P. aeruginosa.

* Corresponding author. Mailing address: Mpex Pharmaceutical Inc., 11535 Sorrento Valley Road, San Diego, CA 92121-1309. Phone: (858) 875-6679. Fax: (858) 875-2851. E-mail: msabet{at}mpexpharma.com

{triangledown} Published ahead of print on 15 June 2009.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3923-3928, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00268-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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