Study design (if review, criteria of inclusion for studies)
Random allocation. Double blinded. Placebo control. Parallel groups.
Participants
520 participants (54% male). Age from six years, 54% 18 years or older. All infected with P. aeruginosa. Baseline FEV1 25-75% predicted. Criteria for CF were CFF clinical practice guidelines.
Interventions
Tobramycin 300 mg or 0.225 normal saline and 1.25 mg quinine twice daily for three 28-day on-off cycles.
Outcome measures
Lung function (FEV1 and FVC), exacerbations (hospitalisation or IV antibiotics), sputum P. aeruginosa colony count, renal toxicity, ototoxicity.
Main results
The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001). The patients in the tobramycin group were 26 percent (95 percent confidence interval, 2 to 43 percent) less likely to be hospitalized than those in the placebo group. Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum. The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group, as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group.
Authors' conclusions
In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.