• J Christian Widere, Claire Leilani Davis, Johanna Jean Loomba, Taison D Bell, Kyle B Enfield, Andrew Julio Barros, and N3C Consortium.
• Department of Medicine, University of Virginia, Charlottesville, VA.
• Crit. Care Med. 2023 Sep 1; 51 (9): 116811761168-1176.

ObjectiveTo investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19.DesignRetrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database.SettingSixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded.PatientsPatients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission.InterventionsNone.Measurements And Main ResultsOf 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42-3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75-2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78-1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23-1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50-1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99-3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37-1.87).ConclusionsAlthough treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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