Nebulized antibiotics in cystic fibrosis

Nebulization is a useful administration route in cystic fibrosis (CF) as it delivers antibiotics directly to the endobronchial site of infection and is associated with decreased toxicity because of limited systemic absorption. It is assumed that the concentration of antibiotics in bronchial secretions should be as high as 10 times the minimum inhibiting concentration to allow penetration of antibiotics into biofilms, suppress inhibitory factors and promote bactericidal effectiveness. However, effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles of a size in the respirable range. Three antibiotics are commonly used for inhalation: tobramycin, amikacin and colistin (colomycin). Placebo-controlled studies evaluating antibiotic aerosol maintenance in stable patients chronically infected with Pseudomonas aeruginosa indicate a significant improvement of lung function and a reduction of the number of hospital admissions for an acute exacerbation of CF. TOBI is a recently marketed preservative- and sulfate-free formula of tobramycin, specially designed for diffusion in the bronchioles and optimal tolerance. A wide-scope study involving 520 patients compared TOBI (300 mg twice daily; n = 258) with placebo (n = 262) for three 28-day cycles with each cycle separated by a 28-day period of no treatment. Respiratory function was significantly improved as early as in the second week and remained so for the rest of the trial even during periods without aerosol treatment. There was also a parallel decrease in the relative risk of hospitalization, the number of days of hospitalization and the number of days on intravenous antipyocyanic treatment. Toxicity studies carried out so far have shown no renal or ototoxicity with nebulized tobramycin. Introduction or selection of resistant bacteria is relatively rare but remains a matter of concern. Aerosol maintenance treatment with an appropriate antibiotic in a high enough dosage can be recommended for patients with CF who are chronically infected with P. aeruginosa.