Faculty Collaboration Database

Testing the effects of combining azithromycin with inhaled tobramycin for P. aeruginosa in cystic fibrosis: a randomised, controlled clinical trial. Thorax 2022 Jun;77(6):581-588

Date

10/29/2021

Pubmed ID

34706982

Pubmed Central ID

PMC9043040

DOI

10.1136/thoraxjnl-2021-217782

Scopus ID

2-s2.0-85125627383 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

RATIONALE: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa. 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 (FEV₁) and greater reduction in P. aeruginosa 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 P. aeruginosa airway infection.

RESULTS: Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV₁ 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 P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log₁₀ CFU/mL; 95% CI: 0.03 to 1.47; p=0.043).

CONCLUSIONS: Despite having greater reduction in P. aeruginosa 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.

Author List

Nichols DP, Singh PK, Baines A, Caverly LJ, Chmiel JF, GIbson RL, Lascano J, Morgan SJ, Retsch-Bogart G, Saiman L, Sadeghi H, Billings JL, Heltshe SL, Kirby S, Kong A, Nick JA, Mayer-Hamblett N, TEACH Study Group

Author

Nicholas Antos MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Inhalation
Anti-Bacterial Agents
Azithromycin
Cystic Fibrosis
Forced Expiratory Volume
Humans
Prospective Studies
Pseudomonas Infections
Pseudomonas aeruginosa
Tobramycin