The Effect of Oral Azithromycin on the Response to Pulmonary Exacerbations Treated with Intravenous Tobramycin in Children with Cystic Fibrosis.

RATIONALE: Intravenous (IV) tobramycin is frequently used to treat pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF), but there is concern that azithromycin may interact with tobramycin making it less effective against Pseudomonas aeruginosa.

OBJECTIVE: 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 CF patients 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 > 90% of baseline (best FEV1 in the previous 6 months). Response to treatment was compared between patients who had received chronic azithromycin (azithromycin users) to those who had not (azithromycin non-users), 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 non-users returned to >90% of baseline FEV1. However, after taking into account that azithromycin users had worse baseline FEV1 compared to azithromycin non-users , relative improvement in FEV1 was 9.5% (95% CI -18.7, -0.3)) lower in azithromycin users compared to azithromycin non-users.

CONCLUSIONS: Although a similar proportion of CF children with chronic P. aeruginosa infection on azithromycin recovered lung function compared to 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 IV tobramycin for PExs.