Article

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 www.clinicaltrials.gov (NCT00677365).

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    • "In the future, more data will become available as three registered phase 2 trials regarding the treatment of VAP [64] and MRSA infection in CF [65] [66] are under way. As assessed by three randomised trials, inhaled fluoroquinolones showed encouraging results in the treatment of chronic infections in patients with CF [59] and bronchiectasis [60] [61]. This effect will be further investigated by six ongoing, registered phase 3 trials regarding aerosolised levofloxacin [67] [68] and ciprofloxacin [69] [70] [71] [72]. "
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    ABSTRACT: We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. Among several inhaled β-lactams, ceftazidime was used with varying success in the prevention and treatment of ventilator-associated pneumonia (VAP) and improved clinical outcomes in chronic Pseudomonas aeruginosa lower respiratory tract infections (LRTIs) in patients with cystic fibrosis (CF) or bronchiectasis. Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.
    International Journal of Antimicrobial Agents 11/2014; 45(3). DOI:10.1016/j.ijantimicag.2014.10.008 · 4.26 Impact Factor
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    • "MP-376 is a novel solution formulation for aerosol administration of LVX, and was developed for patients with cystic fibrosis who have chronic infections due to P. aeruginosa. In one study, this product was used at three doses (120 mg every day, 240 mg every day, 240 mg twice a day) for 28 days, and was well tolerated and demonstrated significant clinical efficacy in heavily treated patients with cystic fibrosis and pulmonary P. aeruginosa infection.28 All doses of MP-376 resulted in reduced density of P. aeruginosa in sputum at day 28, with MP-376 240 mg twice a day showing a 0.96 log difference compared with placebo (P=0.001). "
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    Therapeutics and Clinical Risk Management 03/2014; 10:217-227. DOI:10.2147/TCRM.S59079 · 1.47 Impact Factor
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    • "One RCT assessed the efficacy and safety of a novel aerosol formulation of levofloxacin (MP-376, Aeroquin) in 151 patients with CF with chronic P. aeruginosa infection [62]. The participants received one of three doses of MP-376 (120 mg OD, 240 mg OD, 240 mg BID) or placebo for 28 days. "
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    ABSTRACT: The optimal antibiotic regimen is unclear in management of pulmonary infections due to pseudomonas and staphylococcus in cystic fibrosis (CF). We systematically searched all the published literature that has considered the evidence for antimicrobial therapies in CF till June 2013. The key findings were as follows: inhaled antipseudomonal antibiotic improves lung function, and probably the safest/most effective therapy; antistaphylococcal antibiotic prophylaxis increases the risk of acquiring P. aeruginosa; azithromycin significantly improves respiratory function after 6 months of treatment; a 28-day treatment with aztreonam or tobramycin significantly improves respiratory symptoms and pulmonary function; aztreonam lysine might be superior to tobramycin inhaled solution in chronic P. aeruginosa infection; oral ciprofloxacin does not produce additional benefit in those with chronic persistent pseudomonas infection but may have a role in early or first infection. As it is difficult to establish a firm recommendation based on the available evidence, the following factors must be considered for the choice of treatment for each patient: antibiotic related (e.g., safety and efficacy and ease of administration/delivery) and patient related (e.g., age, clinical status, prior use of antibiotics, coinfection by other organisms, and associated comorbidities ones).
    The Scientific World Journal 12/2013; 2013:645653. DOI:10.1155/2013/645653 · 1.73 Impact Factor
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