Trial Reveals Safer And Simpler Approach To Treating Children With Cystic Fibrosis

Treating chest infections in young cystic fibrosis patients with an antibiotic once instead of three times daily is as effective and less toxic, conclude the results of a randomised trial published in this week’s issue of THE LANCET.

Aminoglycoside antibiotics are widely used for the management of patients who have cystic fibrosis and chronic chest infection with a bacterium called Pseudomonas aerginosa. Currently patients are given aminoglycosides three times daily. The drugs can cause damage to kidney function and hearing loss.

Alan Smyth (University of Nottingham, UK) and colleagues recruited 219 cystic fibrosis patients (125 children and 94 adults) between 1999 and 2003 in the UK. The patients were randomly assigned to receive an aminoglycoside called tobramycin intravenously once or three times daily for 14 days. The researchers measured changes in lung function and found that the two treatments had a similar effect. However in children, the once daily treatment caused fewer kidney related side effects.

Dr Alan Smyth comments: “Our results are likely to affect aminoglycoside prescription in cystic fibrosis in clinical practice. Once daily treatment may be preferred by patients receiving intravenous antibiotics because of its convenience. Antipseudomonal antibiotics are usually given as combinations of two or more drugs in cystic fibrosis because of concerns of emerging antibiotic resistance. Most other antipseudomonal antibiotics need to be given three times daily and so further development of other once daily antibiotics would be useful.”

In an accompanying commentary Heather VandenBussche (Bronson Methodist Hospital, Michigan, USA) and Michael Klepser (Ferris State University College of Pharmacy, Michigan, USA) write that several unanswered questions persist about once daily aminoglycoside dosing in cystic fibrosis patients.

Dr VandenBussche concludes: “ Smyth and colleagues’ report provides some useful insights into the safety and efficacy of once-daily administration of aminoglycosides in patients with cystic fibrosis. However, we need larger and longer studies that include adequate numbers of children and adults. Future studies should evaluate pharmokinetic variables and organism susceptibilities after multiple courses of tobramycin. Such studies would better address concerns about once-daily dosing and its effects on bacterial resistance in patients with cystic fibrosis