Efficacy of inhaled amikacin as adjunct to intravenous combination therapy (ceftazidime and amikacin) in cystic fibrosis. Efficacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis.
Eighty-seven patients with cystic fibrosis were admitted to hospital with an acute exacerbation of pulmonary symptoms associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated to receive intravenously administered ceftazidime (250 mg/kg/day) and amikacin (33 mg/kg/day) alone or with inhaled amikacin (100 mg twice a day). Other aspects of the 2-week treatment were constant. The two therapy groups were comparable in all aspects. At the completion of therapy, the addition of aerosolized amikacin produced temporary eradication of P. aeruginosa in 70% of the patients, compared with 41% in the intravenous therapy only group (P less than 0.02). Suppression of P. aeruginosa in sputum cultures was correlated with the amikacin sputum concentrations. However, both regimens resulted in similar improvements in clinical, radiologic, laboratory, and pulmonary function measurements, and within 4 to 6 weeks most patients were recolonized with P. aeruginosa. There was no serious toxicity or adverse effect. In patients with cystic fibrosis, the addition of aerosol aminoglycoside to systemic antipseudomonal combination therapy is not clinically beneficial. Two forms of treatment of acute pulmonary exacerbations in patients with cystic fibrosis were compared: intravenous ticarcillin (300 mg drug per kg per day) and tobramycin (10 mg drug per kg per day) versus the same intravenous antibiotic therapy plus inhaled tobramycin (80 mg three times per day). The 16 patients in the intravenous plus inhaled tobramycin group were similar to the 12 control patients in age, sex, Schwachman scores, pulmonary function and pretreatment colony counts of Pseudomonas aeruginosa in sputum. Treatment resulted in significant improvement in clinical status and pulmonary function without any apparent differences in the two groups. However, intravenous plus inhaled tobramycin resulted in temporary eradication of P. aeruginosa in 63% of the patients compared to 25% in the intravenous only group (P = 0.03). Suppression of P. aeruginosa in sputum cultures did not correlate with clinical response to treatment. No renal toxicity or elevations of serum tobramycin were observed in the intravenous plus inhaled tobramycin group.
There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.