Antibiotic Treatment in Patients Hospitalized for Nonsevere COVID-19.

Importance: Patients hospitalized with nonsevere COVID-19 continue to receive community-acquired pneumonia (CAP) antibiotic treatment despite a low risk of bacterial coinfection. Unnecessary antibiotic prescribing contributes to global antibiotic resistance and also poses a threat to individual patients. Objective: To examine the association of CAP antibiotic treatment started on admission with clinical outcomes among a large sample of patients hospitalized for nonsevere COVID-19 in hospitals across the US. Design, Setting, and Participants: This retrospective cohort study used a target trial emulation design. Participants were adult, immunocompetent patients admitted to general care for COVID-19 from April 2020 to December 2023 at 1053 US-based acute-care hospitals that contribute data to the Premier Healthcare Database. Patients with nonpneumonia bacterial infections present on admission were excluded. Data were analyzed from April to October 2024. Exposure: Receipt of a CAP antibiotic regimen on the day of admission. Main Outcomes and Measures: The primary outcome was a composite measure of deterioration (vasopressor, high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, intermediate care, intensive care unit admission) and in-hospital mortality occurring on day 2 or later. The association between receipt of antibiotic therapy and the primary outcome was assessed using propensity methods while adjusting for a broad set of potential confounders, including cotreatments. Results: The cohort included 520 405 patients with COVID-19 (median [IQR] age, 66 [53-78] years; 266 186 [51.2%] male), including 92 708 Black patients (17.8%), 63 619 Hispanic patients (12.2%), and 304 649 White patients (58.5%); 279 656 patients (53.7%) had Medicare insurance. A total of 160 482 patients (30.8%) were treated with a CAP antibiotic regimen on day 1 of admission. The primary composite outcome was higher in the CAP group (20.8%) compared with the unexposed (no antibiotic) group (18.4%), but the difference did not meet the predefined criteria for clinical significance (ASD, 4.1%). Patients who received CAP antibiotics had higher odds of poor clinical outcomes (propensity matched-odds ratio [OR], 1.03 [95% CI, 1.01-1.05]; P = .003; inverse probability treatment weighted-OR, 1.03 [95% CI, 1.02-1.05]; P < .001; standardized mortality ratio weighted-OR, 1.10 [95% CI, 1.08-1.12]; P < .001). Conclusions and Relevance: In this large cohort study of patients hospitalized with nonsevere COVID-19, there was no clinically meaningful difference in outcomes with early antibiotic treatment. Given the risks associated with unnecessary antibiotic treatment, these results argue against routine antibiotic use in this population.