Lower respiratory tract infection with Pseudomonas aeruginosa (PA) is associated with increased morbidity in CF patients. Current treatment guidelines for inhaled antibiotics are not universally followed due to the perception of decreased efficacy, increasing resistance, drug intolerance, and high treatment burden with current aerosol antibiotics. New treatment options for CF pulmonary infections are needed.

OBJECTIVE: This study assessed the efficacy and safety of a novel aerosol formulation of levofloxacin (MP-376, AeroquinTM) in a heavily-treated CF population with PA infection.

METHODS: This study randomized 151 CF patients with chronic PA infection to one of 3 doses of MP-376 (120 mg QD, 240 mg QD, 240 mg BID) or placebo for 28 days. The primary efficacy endpoint was the change in sputum PA density. Secondary endpoints included changes in pulmonary function, the need for other anti-PA antimicrobials, changes in patient-reported symptom scores, and safety monitoring.

RESULTS: All doses of MP-376 resulted in reduced sputum PA density at Day 28, with MP-376 240 mg BID showing a 0.96 log difference compared to placebo (P = 0.001). There was a dose-dependent increase in FEV1 (L) for MP-376, with a difference of 8.7% in FEV1 (L) between the 240 mg BID group and placebo (P = 0.003). Significant reductions (61% to 79%) in the need for other anti-PA antimicrobials were observed with all MP-376 treatment groups compared to placebo. MP-376 was generally well tolerated relative to placebo.

CONCLUSION: Nebulized MP-376 was well tolerated and demonstrated significant clinical efficacy in heavily-treated CF patients with PA lung infection.