Testing the effects of combining azithromycin with inhaled tobramycin for P. aeruginosa in cystic fibrosis: a randomised, controlled clinical trial. Issue 6 (27th October 2021)

• Record Type: Journal Article
• Authors: Nichols, David P; Singh, Pradeep K; Baines, Arthur; Caverly, Lindsay J; Chmiel, James F; GIbson, Ronald L; Lascano, Jorge; Morgan, Sarah J; Retsch-Bogart, George; Saiman, Lisa; Sadeghi, Hossein; Billings, Joanne L; Heltshe, Sonya L; Kirby, Shannon; Kong, Ada; Nick, Jerry A; Mayer-Hamblett, Nicole
• Other Names: author non-byline.; Mogayzel Peter author non-byline.; Brown Perry author non-byline.; Sawicki Gregory author non-byline.; Jain Manu author non-byline.; McPhail Gary author non-byline.; McBennett Kimberly author non-byline.; Mueller Gary author non-byline.; Schultz Karen author non-byline.; Millard Susan author non-byline.; Graff Gavin author non-byline.; Ren Clement author non-byline.; Escobar Hugo author non-byline.; Zanni Robert author non-byline.; Keens Thomas author non-byline.; Antos Nicholas author non-byline.; Egan Marie author non-byline.; Walker Patricia author non-byline.; Livingston Floyd author non-byline.; Milla Carlos author non-byline.; Elidemir Okan author non-byline.; Chittivelu Subramanyam author non-byline.; Varlotta Laurie author non-byline.; Pilewski Joseph author non-byline.; Cairns Anne Marie author non-byline.; MacDonald Kelvin author non-byline.; Voter Karen author non-byline.; Asfour Fadi author non-byline.; Conrad Douglas author non-byline.; Goss Christopher author non-byline.; Albers Gary author non-byline.; Pittman Jessica author non-byline.; Kremer Ted author non-byline.; Bondick Irene author non-byline.; Brassil Maggie author non-byline.; Cianciola Missy author non-byline.; Couture Laurel author non-byline.; Dingledine Jeannette author non-byline.; Doyle Martha author non-byline.; Fogarty Barbra author non-byline.; Jacobs Susan author non-byline.; Johnson Miya author non-byline.; Mathewson Barbara author non-byline.; McDonnell Peter author non-byline.; Mead Anna author non-byline.; Myers Matthew author non-byline.; VanDalfsen Jill author non-byline.;
• Is Part Of: Thorax. Volume 77:Issue 6(2022)
• Page Start: 581
• Page End: 588
• Publication Date: 2021-10-27
• Subjects: cystic fibrosis -- bacterial Infection -- respiratory Infection; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2021-217782
• Languages: English
• ISSNs: 0040-6376

Abstract

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.