Pulmonary Outcomes Associated with Long-Term Azithromycin Therapy in Cystic Fibrosis

Abstract

Rationale: Chronic azithromycin is commonly used in cystic fibrosis based on short controlled clinical trials showing reductions in pulmonary exacerbations and improved FEV 1 . Long-term effects are unknown. Objectives: Examine pulmonary outcomes among chronic azithromycin users compared with matched controls over years of use and consider combined azithromycin use in cohorts using chronic inhaled tobramycin or aztreonam. Methods: This retrospective cohort study used the U.S. cystic fibrosis Foundation Patient Registry. Incident chronic azithromycin users were compared with matched controls by FEV 1 % predicted rate of decline and rates of intravenous antibiotic use to treat pulmonary exacerbations. Propensity score methods were utilized to address confounding by indication. Predefined sensitivity analyses based on lung function, Pseudomonas aeruginosa (PA) status, and follow-up time intervals were conducted. Measurements and Main Results: Across 3 years, FEV 1 % predicted per-year decline was nearly 40% less in those with PA using azithromycin compared with matched controls (slopes, −1.53 versus −2.41% predicted per yr; difference: 0.88; 95% confidence interval [CI], 0.30–1.47). This rate of decline did not differ based on azithromycin use in those without PA. Among all cohorts, use of intravenous antibiotics was no different between azithromycin users and controls. Users of inhaled tobramycin and azithromycin had FEV 1 % predicted per-year decline of −0.16 versus nonusers (95% CI, −0.44 to 0.13), whereas users of inhaled aztreonam lysine and azithromycin experienced a mean 0.49% predicted per year slower decline than matched controls (95% CI, −0.11 to 1.10). Conclusions: Results from this study provide additional rationale for chronic azithromycin use in PA-positive patients to reduce lung function decline.

Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses

“…This makes the study of SO 2 and how it affects pulmonary function highly important and clinically relevant. With the increasing evidence for the lung protective capabilities of AZM [29][30][31][32], we decided to pre-treat mice with AZM before applying short term SO 2 exposure and analyze the effect of AZM on prevention or attenuation of initial damage responses and the subsequent immunomodulatory effects on the epithelial barrier.…”

Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

“…The molecule showing the most interesting effects in CF patients is Azithromycin, with an improvement of lung parameters, a decrease of P. aeruginosa infection, and hospitalization duration (Clement et al, 2006;Saiman et al, 2010;Nichols et al, 2020). Prolonged use of small dose Azithromycin was related to a beneficial impact on lung disease expression, well ahead of P. aeruginosa infection.…”

Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy

“…The present study aimed to determine the effects of prolonged exposure of P. aeruginosa biofilms to OligoG CF-5/20 with regard to the evolved genotypic and phenotypic characteristics of different colony morphotypes to determine impact on bacterial evolution. This study also determined the acquisition of resistance to azithromycin (AZM) (an antibiotic commonly used in the treatment of CF) in the presence and absence of sublethal concentrations of OligoG CF-5/20 ( 27 ). Positive impacts of selective pressure on biofilm growth (negative impact for the host) by OligoG CF-5/20 might be expected to manifest themselves by increased development of SCVs and mucoid phenotypes, both of which are associated with increased resistance to antimicrobial therapy.…”