Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Studies Using Aminoglycosides
A multicenter trial of aerosolized tobramycin (Lederle Laboratories; Wayne, NJ) was designed to overcome some of the limitations of previous stud-ies. Seventy-one CF patients with stable pulmonary status were enrolled in a multicenter, doubleblind, placebo-controlled, taste-masked, crossover design study of tobramycin, 600 mg tid, delivered by ultrasonic nebulizer (Ultraneb 100/99; Sunrise Medical HHG; Somerset, PA). This dose effectively achieves sputum tobramycin concentrations > 10 times the minimal inhibitory concentration (MIC*) of all tobramycin-susceptible P aeruginosa, a concentration shown necessary to overcome competitive binding of tobramycin by CF sputum. A 10% improvement in FEV1 during the first 28-day treatment period was noted during tobramycin administration compared with placebo; FEV1 increased by 3.72% predicted in the treatment group compared with a 5.97% decline in control subjects (p < 0.001). This effect continued during the three-period crossover analysis, although the difference between treatment and placebo was less, 4.32% predicted (p = 0.002). order antibiotics online
In addition, during the first 28 days of tobramycin therapy, a 100-fold mean reduction in the density of P aeruginosa in sputum was demonstrated.
Although the study demonstrated efficacy, the high dose and cumbersome ultrasonic nebulizer were not acceptable to patients and health-care providers. Subsequently, two identical phase III randomized, placebo-controlled parallel design studies were conducted to examine the safety and efficacy of preservative-free, nonpyrogenic, sterile 300-mg solution of tobramycin (TOBI; PathoGenesis; Seattle, WA) designed for administration by a specific nebulizer (Pari LC Plus Jet Nebulizer; Pari; Midlothian, VA) and compressor (Pulmo-Aide; Sunrise Medical HHG). Selection criteria for subjects included age > 6 years, colonized with P aeruginosa, not colonized with Burkholderia cepacia, and FEVj < 75% and > 25% predicted. The primary end points were assessment of FEV1, and sputum bacterial density at 28 days, as well as at the end of three cycles (20 weeks). Secondary end points included FVC, rate of hospitalization, and IV antibiotic usage over the 6-month (20 weeks) study period. In total, 520 patients were enrolled at 69 centers and 464 patients completed the trial.