Testing the effects of combining azithromycin with inhaled tobramycin for in cystic fibrosis: a randomised, controlled clinical trial.

RATIONALE

Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill . This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV) and greater reduction in sputum in response to tobramycin.

METHODS

A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and airway infection.

RESULTS

Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: -0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in density differed in favour of the placebo group (difference: 0.75 log CFU/mL; 95% CI: 0.03 to 1.47; p=0.043).

CONCLUSIONS

Despite having greater reduction in density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin.