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.