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An oral antibiotic commonly used to treat children's ear infections can also dramatically improve lung function in people with cystic fibrosis, according to a new study published in the Oct. 1 issue of JAMA. The drug, called azithromycin, could potentially lengthen the lives of patients, who usually succumb to chronic lung infections by their early 30s.

"This therapy could be a great benefit," says Dr. Lisa Saiman, professor of clinical pediatrics and the study's lead author and co-principal investigator. "The lung function of patients with cystic fibrosis deteriorates over time and this deterioration is the major cause of morbidity and mortality in the disease. There are no magic bullets in cystic fibrosis, but to improve or stabilize lung function is wonderful."

"Azithromycin is one of the three pivotal new therapies we've had for cystic fibrosis in the past 10 years," says Dr. Lynne Quittell, director of the Cystic Fibrosis Center and associate clinical professor of pediatrics, who was also involved with the study. "We expect it will improve life expectancy because it delays the decline in lung function."

Mortality in people with cystic fibrosis is due in large part to lung infections with the bacteria Pseudomonas aeruginosa. By age 18, about 80 percent of patients are chronically infected with this pathogen, which promotes an inflammatory response that destroys lung tissue.

Even with advances in antibiotic therapies — which have been responsible for increasing the median survival of patients from 14 in 1969 to 33.4 in 2001 — patients still typically lose 2 percent to 3 percent of their lung function each year.

The new study found that 24 weeks of azithromycin, taken three times a week in conjunction with other daily treatments, increased lung function in the study subjects by 6.2 percent. It also improved patients' weights, halved the number of days spent in the hospital, and reduced the total amount of antibiotics (both intravenous and oral) the patients needed to take. The patients, all of whom were 6 years of age or older, had chronic P. aeruginosa infections and took their regular regimen of aerosol medications, such as the antibiotic TOBI (tobramycin solution for inhalation) and the recombinant drug Pulmozyme, during the study.

The researchers say that unlike these other two treatments for cystic fibrosis available in the past decade, azithromycin is relatively cheap and very easy to use, requiring only three pills per week. TOBI and Pulmozyme cost $10,000 per year and each dose must be inhaled in 10- to 15-minute sessions twice daily with a nebulizer. When added to other daily therapies, a person with cystic fibrosis may spend an hour and a half each morning completing their treatment routine. Azithromycin is also available immediately, having gained FDA approval in 1991.

Though available for the past 12 years, azithromycin wasn't considered for treatment of cystic fibrosis until Japanese researchers showed that a related antibiotic (erythromycin) increased the 10-year survival rate in patients with a similar disease, diffuse panbronchiolitis, from 12 percent to 90 percent. Like cystic fibrosis, people with diffuse panbronchiolitis are frequently infected with P. aeruginosa and die from chronic lung disease.

European researchers recognized the link between the two diseases and conducted small-scale studies in the late 1990s. Larger trials in the United Kingdom and in Australia have reported similar benefits as the present U.S. study, but were not large enough to examine side effects and secondary outcomes such as hospitalizations and reduction in CF-related pulmonary exacerbations. Since Dr. Saiman and her co-principal investigator, Dr. Bruce Marshall of the University of Utah, first reported their results at the national cystic fibrosis meeting last October, sales of azithromycin have increased dramatically. Drs. Saiman and Marshall are planning longer-term safety and efficacy trials.

How azithromycin causes the improvement in lung function is still unknown. The antibiotic can kill stationary phase P. aeruginosa in culture but only had a minimal effect on bacterial density in the study's subjects. The drug also may work to reduce the inflammatory response, but none of the clinical trials found any conclusive evidence to support that notion. Another hypothesis is that azithromycin may decrease the viscosity of the patient's sputum, allowing easier clearance of bacteria-laden mucus from the lungs. Dr. Saiman hypothesizes that the drug may reduce the ability of P. aeruginosa to express virulence factors which would subsequently reduce the neutrophil inflammatory response within the CF lung. She is planning studies that investigate how azithromycin works.

– SUSAN CONOVA

This study was supported by the Cystic Fibrosis Foundation.


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