Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with
Pseudomonas aeruginosa.
Author(s): Geller DE, Flume PA, Staab D, Fischer R, Loutit JS, Conrad DJ; Mpex 204 Study
Group.
Collaborators: Dozor A, Gherson I, Berlinski A, Brady P, Stone A, Moen S,
Morrissey B, Vlastelin E, Nickerson B, Yagi N, Conrad C, Dunn C, Davis Z, Daines
C, Molina O, Nakamura C, Melvin T, Yoshikawa R, Brown D, Johnson B, Geller D,
Kesser B, Price A, Stokes D, Culbreath B, Vatter S, Conrad D, Munden B, Homnick
D, Wallace N, Wyman E, Shay G, Lee J, Acton J, Duan L, Royall J, Groff J, Hoag J,
Hillman J, Billings J, Grover T, Rosen J, Mokhiber K, McCoy K, Raterman L, Sindel
L, Cowan T, Hemphill M, Woo M, Keens T, Fukushima L, Maloy K, Salathe M, Cubillos
F, Dubin P, Hartigan E, Hurban S, Flume P, Byars T, Antonio S, Fornos P, Phillips
T, Amaro-Glavez R, Hoeft J, Morton R, Richardson K, Arbor A, Nasr S, Kruse D,
Reyes S, Orf T, Fiel S, Cahill C, Boas S, Jernagin C, Lake S, Liou T, Packer K,
Spencer T, Leone E, Schuler D, Geidel C, Ruckes-Nilges C, Staab D, Nagel C,
Riethmuller J, Evers-Bischoff A, Fischer R, Kerscher M, Wagner T, Wortmann I,
Kohlhaeufl M, Bewig B, Rohweder S, Teschler H, Conrad C, Reijers M, Cuppen F,
Weersink E, Illbrink GJ.
Affiliation(s): Nemours Children's Clinic, Orlando, FL 32801, USA. dgeller@nemours.org
Publication date & source: 2011, Am J Respir Crit Care Med. , 183(11):1510-6
RATIONALE: 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.
OBJECTIVES: 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.
METHODS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: 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).
|