Abstract
Chronic pulmonary infections are common among patients with cystic fibrosis. By 10 years of age, Pseudomonas aeruginosa is the predominant pathogen. Inhaled levofloxacin solution (MP-376) is a promising new therapy that exhibits rapid antibacterial activity and excellent biofilm penetration against P. aeruginosa. In the largest trial to date, 151 patients were randomized to receive MP-376 or placebo. At the end of the 28-day treatment period, patients who received MP-376 had decreased P. aeruginosa density in sputum, improved lung function parameters and improved respiratory symptoms. MP-376 also appeared to be safe and well tolerated. The results of two recently completed Phase III trials have not yet been released; however, these data will be critical in determining whether MP-376 is a safe and effective maintenance therapy for chronic pulmonary P. aeruginosa infections among patients with cystic fibrosis.
Disclaimer
At the time of writing, the results of two recently completed Phase III trials had not been released. These trials were designed to demonstrate the safety and effectiveness of MP-376 in improving lung function parameters and increasing the time to the next pulmonary exacerbation. The results of these trials are needed before regulators and clinicians can weigh the evidence for the routine clinical use of MP-376 for the treatment of chronic Pseudomonas aeruginosa infections for patients with cystic fibrosis.
Financial & competing interests disclosure
C Stockmann is supported by the American Foundation for Pharmaceutical Education’s Clinical Pharmaceutical Sciences Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
The pulmonary manifestations of cystic fibrosis emerge early in life and are driven by inflammation, impaired mucociliary clearance and the development of chronic infections.
Chronic pulmonary infections are associated with an increase in sputum production, a decline in lung function, weight loss and respiratory distress.
One of the most common bacterial pathogens associated with chronic pulmonary infections among patients with cystic fibrosis is Pseudomonas aeruginosa, which is a biofilm-forming Gram-negative organism that is challenging to eradicate.
Inhaled antibiotics offer the opportunity to achieve targeted drug delivery to the site of infection in the lungs. This results in a higher concentration of drug in the airway and a lower concentration of drug in the systemic circulation, thereby maximizing the antibacterial effectiveness of the drug while minimizing its potential for toxicity.
Levofloxacin is a member of the fluoroquinolone class of broad-spectrum antibiotics. Levofloxacin displays potent activity against biofilm-forming P. aeruginosa.
In several small Phase I and II clinical trials, patients who were randomized to receive inhaled levofloxacin solution (Aeroquin, MP-376) had decreased sputum P. aeruginosa density, improved lung function parameters and improved respiratory symptoms at the end of a 28-day treatment period.
MP-376 was found to feature a favorable safety profile; however, nearly all patients reported dysgeusia after inhalation of the drug.