Posts
NEW YORK (Reuters Health) Dec 12 - Fosfomycin/tobramycin for inhalation (FTI) is a promising treatment for cystic fibrosis patients with chronic Pseudomonas aeruginosa airway infection and reduced lung function, researchers say.
Their phase II safety/efficacy study tested 28 days of FTI against placebo, immediately following 28 days of inhalation therapy with aztreonam.
Such continuous therapy is not typical. As the authors point out, "a 28-days 'on' and 28-days 'off' dosing schedule is used for inhaled antibiotics that are currently approved in the U.S. for airway P. aeruginosa in cystic fibrosis patients.
But the rationale for the "off" period is being questioned because of changing microbiological profiles and the increasing use of two or more inhaled antibiotics in rotation, they wrote online November 17 in the American Journal of Respiratory and Critical Care Medicine.
Both FTI and the aztreonam inhalation solution are being developed by Gilead Sciences, which sponsored the current trial.
Altogether researchers enrolled 119 patients (average age, 32 years) with a mean forced expiratory volume in one second (FEV1) of 49% predicted at screening.
After the 28-day open-label course of inhaled aztreonam three times daily, patients were randomly allocated to twice-daily FTI (60/40 mg or 80/20 mg) or placebo, for another 28 days.
With aztreonam, the mean improvement in FEV1 predicted was 7.0%. This improvement was maintained with FTI, whereas lung function in placebo-treated patients declined toward pre-aztreonam levels. The treatment effect favoring FTI 160/40 mg was 6.2% (p=0.002) and 7.5% favoring FTI 80/20 mg (p<0.001).
In addition, the researchers found reductions in mean P. aeruginosa sputum density in the FTI 80/20 group versus placebo (p=0.01).
FTI "was also effective against methicillin-resistant Staph aureus, for which there are relative fewer drugs," first author Dr. Bruce Trapnell, of University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Ohio, told Reuters Health.
He and his colleagues found that in 13 of 63 patients co-infected with S. aureus and P. aeruginosa, S. aureus could not be cultured from the end of the FTI treatment period (day 28) through the end of follow-up on day 56.
"However, the study was not set up or powered to evaluate this outcome," Dr. Trapnell cautioned. "The data should be considered supportive, but further studies are needed."
Fosfomycin is a phosphonic acid antibiotic active against gram-positive, gram-negative, and anaerobic bacteria. Tobramycin is an aminoglycoside with gram-negative activity.
"Adverse events, primarily cough," were noted, the authors say. Respiratory events, including dyspnea and wheeze, were less common with FTI 80/20 than FTI 160/40. All respiratory events were mild or moderate in severity, and there were no clinically significant changes in laboratory values.
Along with sponsorship by Gilead Sciences, Inc., the study was supported by grants from the FDA and the NIH General Clinical Research Center.
SOURCE: http://bit.ly/vjcVCR
Original article: http://www.medscape.com/viewarticle/755291?src=nl_topic
