Association of Inhaled Antibiotics in Addition to Standard Intravenous Therapy and Outcomes of Pediatric Inpatient Pulmonary Exacerbations

Rationale: Considerable morbidity and disease progression in people with cystic fibrosis (CF) result from pulmonary exacerbations (PExs). PEx guidelines note insufficient evidence to recommend for or against the concomitant use of inhaled and intravenous antibiotics.Objectives: We hypothesize that the addition of inhaled antibiotics for PEx therapy is associated with improvements in lung function and a longer time to next PEx compared with standard intravenous antibiotics alone.Methods: We performed a retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. People with CF were included if they were hospitalized for PEx between 2006 and 2016 and 6 to 21 years of age. Lung function outcomes were assessed by linear mixed effect modeling and generalized estimating equations. The time to next PEx was assessed by Cox proportional hazards regression. To estimate independent causal effects while accounting for indication bias and other confounders, inverse probabilities of treatment weights were calculated based on covariates believed to influence the likelihood of inhaled antibiotic use during PEx treatment.Results: A total of 3,253 children and adolescents contributed 9,040 PEx events for analysis. Inhaled antibiotics were used in 23% of PEx events but were not associated with better pre- to post-PEx percent predicted forced expiratory volume in 1 second responses (mean difference, -1.11%; 95% confidence interval [CI], -1.83 to -0.38; P = 0.003), higher odds of returning to lung function baseline (odds ratio, 0.94; 95% CI, 0.82 to 1.07; P = 0.34), or longer time to next PEx (hazard ratio, 1.05; 95% CI, 0.99 to 1.12; P = 0.098).Conclusions: The addition of inhaled antibiotics to standard intravenous antibiotic PEx treatment was not associated with improved lung function outcomes or a longer time to next PEx.