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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.

SUBMITTER: Somayaji R

PROVIDER: S-EPMC6600836 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Project description:Rationale: Pulmonary exacerbations (PExs) are associated with significant morbidity in people with cystic fibrosis (CF). Severe PExs are treated with intravenous 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.Objectives: To determine whether, among PEx treated with intravenous tobramycin, concomitant AZM use is associated with worse clinical outcomes.Methods: Retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System (CFFPR-PHIS)-linked dataset. People with CF age 6-21 years were included if they were hospitalized between 2006 and 2016 for a PEx. Inverse probability of treatment weighing was used 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.Results: Among the 10,660 people with CF included in the CFFPR-PHIS-linked dataset, 2,294 children and adolescents with 5,022 PExs that had intravenous tobramycin use were identified. A little less than half (n = 2,247; 45%) of all PExs were treated concomitantly with AZM and intravenous tobramycin. AZM use both at the most recent outpatient clinic encounter and during PEx treatment in combination with intravenous tobramycin was associated with a significantly lower absolute improvement in percentage-predicted forced expiratory volume in 1 second (ppFEV1) (-0.93%; 95% confidence interval [CI], -1.78 to -0.07; P = 0.033), a lesser odds of returning to 90% or more of baseline ppFEV1 (odds ratio, 0.79; 95% CI, 0.68-0.93; P = 0.003), and a shorter time to next PEx requiring intravenous antibiotics (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < 0.001) compared with intravenous tobramycin use without concomitant AZM.Conclusions: Concomitant AZM and intravenous tobramycin use for in-hospital PEx treatment was associated with poorer clinical outcomes than treatment with intravenous tobramycin without AZM. These results support the hypothesis that an antagonistic relationship between these two medications might exist.

Dataset Information

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

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