Clinical importance of special aerosol formulation of tobramycin for treatment of chronic pulmonary disease in patients with cystic fibrosis

The aim of this study was to evaluate clinical efficacy and safety of highly concentrated inhaled solution of tobramycin (Bramitob^®, Chiesi Farmaceutici S.p.A., Italy) in patients with cystic fibrosis (CF). This was 24-wk multicenter international double-blind placebo-controlled randomized trial in parallel groups. In this study, 247 patients aged 6–45 yrs with Pseudomonas aeruginosa yielded in sputum and FEV 1 40 % to 80 % pred. were randomized in 2 groups: those inhaling aerosol tobramycin (161 patients, mean age, 14.8 ± 5.7 yrs) or placebo (84 patients, mean age, 14.7 ± 6.6 yrs). Tobramycin 300 mg b.i.d. was given at the time of basic and antipseudomonal therapy. Efficacy criteria were as follows: lung ventilation parameters, sputum culture and yielding P. aeruginosa, rate of exacerbations of pulmonary disease, rate of hospitalisations, number of workoff or school-off days, number of courses of parenteral tobramycin and other antipseudomonal antibiotics, nutritional status (weight, BMI). Safety profile included serum creatinine level, audiometric test, vital signs (heart rate, blood pressure) and adverse events. To the end of the study, FEV1  improved by 7 % in the tobramycin group and by 1 % in the placebo group (p < 0.001), FVC improved by 5.7 and 1.3 %, respectively (p = 0.002), and FEF 25–75 improved by 8.8 % and 0.7 %, respectively (p = 0.001). Frequency of P. aeruginosa eradication differed significantly between the groups to the end of 4th and 20th weeks of the study (30.8 % vs. 14.3 %; p = 0.011, and 33.3 % vs. 16.5 %; p = 0.024, respectively). Exacerbations of pulmonary disease occurred in 39.8 % of tobramycin patients and in 51.2 % of placebo patients (р = 0.09). Hospital admission was required in 18.6 % and 36.9 % of patients, respectively (p = 0.002). Parenteral tobramycin was administered to 6.2 % and 16.7 % of patients, respectively (p = 0.009), other antipseudomonals were given in 55.9 % and 70.2 % of the patients, respectively (p = 0.029). Number of patients with missing work/school days due to exacerbation of pulmonary disease was 32.3 % in tobramycin group and 57.1 % in placebo group (p < 0.001). Serious adverse events related to treatment with tobramycin were not noted. In conclusion, long-term intermittent treatment with inhaled solution of tobramycin additionally to basic and antipseudomonal therapy in CF patients significantly improved lung ventilation and eradication of P. aeruginosa, decreased the rate of exacerbations of pulmonary disease, rate of hospitalisations, and numbers of antipseudomonal courses and missing work days. The treatment was well tolerated and could be recommended for CF patients with P. aeruginosa in culture.

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