Oral Azithromycin and Response to Pulmonary Exacerbations Treated with Intravenous Tobramycin in Children with Cystic Fibrosis

Rationale: Intravenous tobramycin is frequently used to treat pulmonary exacerbations (PExs) in patients with cystic fibrosis (CF), but there is concern that azithromycin may interact with tobramycin, making it less effective against Pseudomonas aeruginosa. Objectives: The objective of this study was to determine whether oral azithromycin use was associated with worse lung function response to intravenous tobramycin treatment for PExs in a cohort of pediatric patients with CF with chronic P. aeruginosa infection. Methods: Pediatric patients from the Toronto CF database were included if they had at least one PEx and had chronic P. aeruginosa infection. Response to treatment was defined as change in forced expiratory volume in 1 second (FEV1) from start to end of treatment as well as recovery of FEV1 to greater than or equal to 90% of baseline (best FEV1 in the previous 6 mo). Response to treatment was compared between patients who had received chronic azithromycin (azithromycin users) and those who had not (azithromycin nonusers), using marginal structural modeling to account for baseline FEV1 as both a confounder and mediator. Results: There were 67 exacerbations (33 patients). Overall, 69% of azithromycin users and 61% of azithromycin nonusers returned to greater than or equal to 90% of baseline FEV1. However, after taking into account that azithromycin users had worse baseline FEV1 than azithromycin nonusers, relative improvement in FEV1 was 9.5% (95% confidence interval, 218.7 to 20.3) lower in azithromycin users than azithromycin nonusers. Conclusions: Although a similar proportion of children with CF with chronic P. aeruginosa infection on azithromycin recovered lung function compared with those not on azithromycin, when we consider these patients are sicker, azithromycin use was associated with less improvement in relative (but not absolute) FEV1 in patients treated with intravenous tobramycin for PExs.