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Association of Antibiotic Treatment With Outcomes in Patients Hospitalized for an Asthma Exacerbation Treated With Systemic Corticosteroids

Educational Objective
To determine the association of antibiotic treatment with outcomes among patients hospitalized for asthma and treated with corticosteroids.
1 Credit CME
Key Points

Question  Among patients hospitalized for an asthma exacerbation and treated with corticosteroids, is the addition of antibiotic therapy associated with better outcomes?

Findings  In this cohort study of 21 628 patients hospitalized for an asthma exacerbation and treated with corticosteroids, 8927 (41.3%) received antibiotics on day 1 of hospitalization. Compared with patients who were not treated with antibiotics, treated patients had a statistically significantly longer but not clinically important increase in hospital stay, higher hospital cost, lower rate of treatment failure, and no significant difference in risk of antibiotic-related diarrhea.

Meaning  Antibiotic treatment may be associated with marginally longer length of stay but lower risk of treatment failure in adult patients hospitalized for asthma treated with corticosteroids.

Abstract

Importance  Although professional society guidelines discourage use of empirical antibiotics in the treatment of asthma exacerbation, high antibiotic prescribing rates have been recorded in the United States and elsewhere.

Objective  To determine the association of antibiotic treatment with outcomes among patients hospitalized for asthma and treated with corticosteroids.

Design, Setting, and Participants  Retrospective cohort study of data of 21 628 adults hospitalized for asthma exacerbation and treated with systemic corticosteroids in 540 US acute care hospitals from January 1, 2015, through December 31, 2016.

Exposures  Early antibiotic treatment, defined as treatment with an antibiotic initiated during the first 2 days of hospitalization. Patients not treated with antibiotics or treated on day 2 or later were included in the nontreated/late-treated group. Patients with documented infection diagnosed at admission were excluded.

Main Outcomes and Measures  The primary outcome measure was hospital length of stay. Other outcomes included treatment failure (initiation of mechanical ventilation, transfer to the intensive care unit after hospital day 1, in-hospital mortality, or readmission for asthma within 30 days of discharge), hospital costs, and antibiotic-related diarrhea. Multivariable adjustment, propensity score matching, propensity weighting, and instrumental variable analysis were used to assess the association of antibiotic treatment with outcomes.

Results  Of the 21 628 patients, the median (interquartile range [IQR]) age was 46 (33-59) years, 15 662 (72.4%) were women and 9616 (44.5%) were White, and Medicare was the primary form of health insurance for 5499 (25.4%). Antibiotics were prescribed for 8927 patients (41.3%) on day 1; 3022 patients (14.0%) were started after day 1. Compared with patients not treated with antibiotics or treated after day 1, patients treated with antibiotics on day 1 were older (median [IQR] age, 48 [35-60] vs 45 [32-57] years), more likely to be White (48.7% vs 41.5%) and smokers (4.5% vs 3.2%), and had a higher number of comorbidities (eg, congestive heart failure, 5.7% vs 5.4%). Those treated with antibiotics on day 1 had a statistically significant longer hospital stay compared with those not treated on day 1 (mean [SD], 2.81 [2.27] vs 2.57 [2.45] days; difference, 0.11 days, 95% CI, 0.03 to 0.19; median [IQR] 2 [1-4] vs 2 [1-3] days). In propensity score–matched analysis, receipt of antibiotics on day 1 was associated with a marginally longer but not clinically meaningful increase in hospital stay (length of stay ratio, 1.06; 95% CI, 1.04 to 1.09), higher cost of hospitalization (median [IQR] cost, $4320 [$2754-$6716] vs $3861 [$2479-$6236]) but lower risk of treatment failure (7.1% vs 8.2%; difference, −1.08%, 95% CI, −1.93% to −0.24%; adjusted OR, 0.86; 95% CI, 0.77 to 0.97). Multivariable adjustment, propensity score weighting, and instrumental variable analysis yielded similar results.

Conclusions and Relevance  Among adult patients hospitalized for asthma exacerbation and treated with corticosteroids, antibiotic therapy initiated on day 1 of hospitalization was associated with a slightly longer but not clinically important increase in hospital length of stay, higher hospitalization cost, and lower risk of treatment failure. These findings highlight the need to perform randomized clinical trials to determine the role of antibiotic prescribing among patients hospitalized for asthma exacerbation.

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Article Information

Accepted for Publication: August 20, 2018.

Published Online: January 28, 2019. doi:10.1001/jamainternmed.2018.5394

Retraction and Replacement: This article was retracted and replaced on January 19, 2021, to fix errors in the abstract, key points, text, tables, figure, and Supplement 1 (see Supplement 2 for the retracted article with errors highlighted and Supplement 3 for the replacement article with corrections highlighted).

Corresponding Author: Mihaela S. Stefan, MD, PhD, Institute for Healthcare Delivery and Population Science, Department of Medicine, University of Massachusetts Medical School, Baystate, 3601 Main St, Third Floor, Springfield, MA 01199 (mihaela.stefan@baystatehealth.org).

Author Contributions: Dr Stefan had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Stefan, Au, Lindenauer.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Stefan, Au, Lindenauer.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Stefan, Shieh, Pekow.

Obtained funding: Stefan, Lindenauer.

Administrative, technical, or material support: Stefan, Spitzer, Lindenauer.

Supervision: Stefan, Pekow, Lindenauer.

Conflict of Interest Disclosures: Dr Krishnan reported serving on a data monitoring committee for Sanofi and receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute. Dr Au reported serving on a data monitoring committee for Novartis, serving as a consultant to Gilead Sciences, serving on the pulmonary examination writing committee for the American Board of Internal Medicine, and serving as Deputy Editor for the Annals of the American Thoracic Society. Dr Lindenauer reported receiving grant support from the National Heart, Lung, and Blood Institute. No other disclosures were reported.

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