Effect of Concomitant Azithromycin and Tobramycin Use on Cystic Fibrosis Pulmonary Exacerbation Treatment.

Pulmonary exacerbations (PEx) are associated with significant morbidity in people with cystic fibrosis (CF). Severe PEx are treated with IV antibiotics, including tobramycin. CF care guidelines recommend continuing chronic maintenance medications during PEx treatment. Azithromycin (AZM) is one of the most widely prescribed chronic medications for CF in the United States. Recent evidence has identified a potential antagonistic relationship between AZM and tobramycin.
To determine if, among PEx treated with intravenous (IV) tobramycin, concomitant AZM use is associated with worse clinical outcomes.
Retrospective cohort study utilizing the CF Foundation Patient Registry- Pediatric Health Information System (CFFPR-PHIS) linked dataset. People with CF age 6-21 years were included if hospitalized between 2006 and 2016 for a PEx. Inverse probability of treatment weighing was utilized to minimize the effects of confounders, including indication bias. Associations of concomitant treatment with AZM and lung function outcomes were determined using linear mixed effect models and generalized estimating equations. Cox proportional hazard regression models were used to evaluate associations with time to next PEx.
Among the 10,660 people with CF included in the CFFPR-PHIS linked dataset, 2,294 children and adolescents with 5,022 PEx that had IV tobramycin use were identified. A little less than half (N=2,247; 45%) of all PEx were treated concomitantly with AZM and IV tobramycin. AZM use both at the most recent outpatient clinic encounter and during PEx treatment in combination with IV tobramycin was associated with a significantly lower absolute improvement in percent predicted forced expiratory volume in 1 second (ppFEV1) (-0.93%, [95% CI -1.78, -0.07]; p=0.033), a lesser odds of returning to ≥90% of baseline ppFEV1 (OR 0.79, [95% CI 0.68, 0.93]; p=0.003), and a shorter time to next PEx requiring IV antibiotics (Hazard Ratio 1.22, [95% CI 1.14, 1.31]; p=<0.001) compared to IV tobramycin use without concomitant AZM.
Concomitant AZM and IV tobramycin use for in-hospital pediatric PEx treatment was associated with poorer clinical outcomes than treatment with IV tobramycin without AZM. These results support the hypothesis that an antagonistic relationship between these two medications might exist.