Patients hospitalized with non-severe 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, say Pulia, et al. (2025) who sought to examine the association of CAP antibiotic treatment started on admission with clinical outcomes among a large sample of patients hospitalized for non-severe COVID-19 in hospitals across the U.S.

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).

In this large cohort study of patients hospitalized with non-severe 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.

Reference: Pulia MS, et al. Antibiotic Treatment in Patients Hospitalized for Non-severe COVID-19. JAMA Netw Open. 2025;8(5):e2511499. doi:10.1001/jamanetworkopen.2025.11499