Oral Azithromycin Use and the Recovery of Lung Function from Pulmonary Exacerbations Treated with Intravenous Tobramycin or Colistimethate in Adults with Cystic Fibrosis

Abstract Rationale The potential of azithromycin to alter the antimicrobial and clinical benefits of inhaled tobramycin in patients with cystic fibrosis (CF) has been previously reported. The potential interaction between azithromycin and intravenous antibiotics in the treatment of pulmonary exacerbations is unknown. Objectives To determine if chronic azithromycin use as a concomitant therapy is associated with change in lung function after receiving intravenous antibiotic regimens including tobramycin or colistimethate. Methods This was a retrospective cohort study evaluating the association of azithromycin with intravenous tobramycin or colistimethate in adult patients with CF treated for a pulmonary exacerbation. The primary outcome was relative lung function recovery (forced expiratory volume in 1 s [FEV1]) after exacerbation treatment. Generalized estimating equations were applied to account for repeated events with independent correlation structures and robust standard errors, incorporating several confounders. Results A total of 220 exacerbation events occurred in 121 patients in the tobramycin group (47% using azithromycin), and 207 exacerbation events occurred in 86 patients in the colistimethate group (59% using azithromycin). Azithromycin use was associated with less FEV1% recovery in patients treated with tobramycin (−3% relative FEV1% recovery [95% confidence interval (CI), −7 to 0.2] and −2.64% absolute FEV1% change [95% CI, −4.52 to −0.76]). Azithromycin use was associated with greater recovery of FEV1% when treated with colistimethate (+3% relative FEV1% recovery [95% CI, −0.1 to 7] and 2.00% absolute improvement in FEV1% [95% CI, 0.13 to 3.87]). The odds of 90% or 100% recovery to baseline FEV1% were lower with azithromycin use in the tobramycin cohort and higher with azithromycin use in the colistimethate cohort but were not statistically significant. Conclusions Azithromycin use was associated with a more favorable response in adult patients with CF treated with intravenous colistimethate but a less favorable response in those treated with intravenous tobramycin.