Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa.

Nemours Children's Clinic, Orlando, FL 32801, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 02/2011; 183(11):1510-6. DOI: 10.1164/rccm.201008-1293OC
Source: PubMed

ABSTRACT Lower respiratory tract infection with Pseudomonas aeruginosa (PA) is associated with increased morbidity in patients with cystic fibrosis (CF). 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.
This study assessed the efficacy and safety of a novel aerosol formulation of levofloxacin (MP-376, Aeroquin) in a heavily treated CF population with PA infection.
This study randomized 151 patients with CF with chronic PA infection to one of three doses of MP-376 (120 mg every day, 240 mg every day, 240 mg twice a day) 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.
All doses of MP-376 resulted in reduced sputum PA density at Day 28, with MP-376 240 mg twice a day showing a 0.96 log difference compared with placebo (P = 0.001). There was a dose-dependent increase in FEV(1) for MP-376, with a difference of 8.7% in FEV(1) between the 240 mg twice a day group and placebo (P = 0.003). Significant reductions (61-79%) in the need for other anti-PA antimicrobials were observed with all MP-376 treatment groups compared with placebo. MP-376 was generally well tolerated relative to placebo.
Nebulized MP-376was well tolerated and demonstrated significant clinical efficacy in heavily treated patients with CF with PA lung infection. Clinical trial registered with (NCT00677365).

  • [Show abstract] [Hide abstract]
    ABSTRACT: Much of the improvement in the survival of individuals with cystic fibrosis (CF) is due to advancements in antimicrobial treatments. New aerosolized antibiotic formulations have recently been introduced (such as inhaled aztreonam), and others are in development (inhaled levofloxacin and liposomal amikacin). Licensed dry powder formulations include tobramycin inhalation powder and dry powder colistimethate (available in Europe). Although inhaled antibiotics have the advantage of being able to deliver high intrapulmonary concentrations of drug, antimicrobial resistance can still develop and is a concern in CF. Antimicrobial resistance might be mitigated by using non-antibiotic treatments, antibiotic adjuvants, which have activity against bacteria. Examples include agents such as gallium, antimicrobial peptides and anti-biofilm compounds such as alginate oligosaccharides (OligoG) and garlic. Vaccination strategies and antibody therapy (IgY) against Pseudomonas aeruginosa have also been attempted to prevent initial infection with this organism in CF. Although aggressive and long-term use of antibiotics has been crucial in slowing lung function decline and improving survival in people with CF, it has added a significant burden of care and associated toxicities in these individuals. Careful surveillance and the use of preventative strategies for antibiotic related toxicity (such as nephrotoxicity and ototoxicity) are essential. Continued development of effective antimicrobial agents that can function in the conditions encountered in the CF lung, such as against bacterial biofilm growth and under anaerobic conditions, is needed. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 02/2015; DOI:10.1016/j.jcf.2015.02.005 · 3.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inhaled antimicrobials provide a promising alternative to the systemically delivered drugs for the treatment of acute and chronic lung infections. The delivery of antimicrobials via inhalation route decreases the systemic exposure while increasing the local concentration in the lungs enabling the use of antimicrobials with severe systemic side effects. The inhalation route of administration has several challenges in pharmacokinetics (PK) and pharmacodynamics (PD) assessments. This review discusses various issues that need to be considered during study, data analysis and interpretation of PK and PD of inhaled antimicrobials. Advancements overcoming the challenges are also discussed. Copyright © 2015. Published by Elsevier B.V.
  • Source