Once-daily tobramycin safe for cystic fibrosis

Once-daily treatment with the intravenous antibiotic tobramycin for lung flare-ups in patients with cystic fibrosis appears to be as effective and perhaps less toxic to the kidneys than treatment three times a day, especially in children, British investigators report.

Aminoglycoside antibiotics, such as tobramycin, are widely used to treat bacterial lung infections in cystic fibrosis patients, Dr. Alan Smyth, at the University of Nottingham, and his study group, explain in this week's issue of The Lancet. However, these drugs can be toxic to the kidneys and the inner ear.

Smyth's group theorized that once-daily dosing with tobramycin might be safer and just as effective as dosing three times a day.

To investigate, they enrolled patients with cystic fibrosis being treated for a bacterial lung infection due to Pseudomonas aeruginosa. A total of 107 patients (61 children) were randomly assigned to once-daily treatment and 112 (64 children) were assigned to thrice-daily treatment. The patients also received ceftazidime three times a day during the 14-day trial period.

There appeared to be no difference in the effectiveness between the two treatment schedules, with no differences in results of lung function tests, symptom test scores or clinical findings.

Measures of kidney dysfunction fell during once-daily treatment and rose during thrice-daily treatment, with differences reaching statistical significance in children.

The potential to reduce kidney toxicity is an important advantage of a once-daily regimen of intravenous tobramycin. However, the beneficial effects may not be significant in patients older than 16 years, Smyth and his associates conclude.

While this study "provides some useful insight into the safety and efficacy of once-daily administration of aminoglycosides in patients with cystic fibrosis," larger and longer studies are needed to better address concerns about once-daily dosing, write Dr. Heather L. VandenBussche and Dr. Michael Klepser, at Ferris State University College of Pharmacy in Kalamazoo, Michigan, in an accompanying editorial.

SOURCE: The Lancet, February 12, 2005.