Cystic fibrosis · Inhaled antibiotics
Intermittent administration of inhaled tobramycin in patients with cystic fibrosis
| Design | Two randomised, double-blind, placebo-controlled trials |
|---|---|
| Treatment | Inhaled tobramycin 300 mg twice daily in alternating 28-day on-off cycles |
| Control | Placebo |
| Population | 520 patients with cystic fibrosis and Pseudomonas aeruginosa infection |
| Follow-up | 24 weeks |
| Primary endpoint | Change in FEV1 at week 20 |
| Result | FEV1 rose by an average of 10% at week 20 in the tobramycin group and fell by 2% with placebo (p<0.001). Sputum Pseudomonas density fell by 0.8 log10 CFU/g with tobramycin and rose by 0.3 log10 CFU/g with placebo (p<0.001). Tobramycin-treated patients were significantly less likely to be hospitalised. |
| Secondary endpoints | Sputum Pseudomonas density, hospitalisation, intravenous antibiotic use, ototoxicity and nephrotoxicity |
In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.
The trial authors, in the published abstract
Established the alternating month-on, month-off cycle that inhaled antibiotic therapy still follows, chosen to limit resistance. A 10% FEV1 gain is large for a chronic suppressive antibiotic. The equivalent strategy in non-CF bronchiectasis has been far less convincing (PROMIS).
Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999 Jan 7;340(1):23-30.