Efficacy and safety of aerosolized tobramycin in cystic fibrosis.

Aerosolized tobramycin has been extensively used in cystic fibrosis (CF) patients in order to directly deliver the antibiotic to the endobronchial site of infection, and decrease toxicity by limiting systemic absorption. Aerosolized tobramycin doses ranging from 80 mg twice or three times daily to 600 mg three times daily have been used in various clinical trials. At an 80-mg dose, preservation of pulmonary function with little or no improvement over the baseline was reported. Tobramycin, nebulized at 600 mg three times daily, significantly improved clinical and pulmonary functions and reduced the density of Pseudomonas aeruginosa in the sputum. No ototoxicity or nephrotoxicity was reported at either dose. TOBI, a tobramycin solution for inhalation, received Food and Drug Administration approval for maintenance treatment of P. aeruginosa lung infections in CF patients at least 6 years of age. Patients received TOBI nebulize 300 mg of tobramycin every 12 hr daily for 28 days, followed by 28 days off the drug in alternating cycles. In phase III trials, TOBI improved pulmonary function and decreased sputum density of P. aeruginosa compared to placebo. Serum creatinine was minimally, transiently elevated in both groups. More patients in the TOBI group reported voice alterations. All reports of tinnitus were in the TOBI group. An increased risk of emergence of resistant strains of P. aeruginosa was noted at all doses, after prolonged use.