The Argument Against Routine Antibiotics for Patients With Nonsevere COVID-19

Over 500,000 US patients hospitalized with nonsevere COVID-19 saw no clinically significant benefit and potential harm associated with routine early antibiotic treatment, supporting antibiotic stewardship to limit unnecessary use. | Image Credit: Production Perig - stock.adobe.com

Early antibiotic treatment showed no meaningful benefit for hospitalized patients with nonsevere COVID-19 and may even be linked to worse outcomes, challenging the high rates of antibiotic use observed during the pandemic for this patient group, according to a study published in JAMA Network Open.1

Reports indicate that since the COVID-19 pandemic, inpatients have received antibiotics at higher rates (>30%) than the average 5% of cases involving confirmed bacterial coinfections. The World Health Organization has declared antimicrobial resistance a top global public health and development threat.2 The misuse and overuse of antimicrobials in humans, animals, and plants mainly cause the development of drug-resistant pathogens.

The COVID-19 pandemic has introduced unprecedented challenges in primary care. One analysis showed a significant 9.5% increase in antibiotic utilization in primary care.3 Unnecessary antibiotic prescribing also threatens individual patients due to the risk of serious adverse drug events and Clostridioides difficile colitis.1

Researchers conducted a retrospective cohort study using a target trial emulation design to examine the association of community-acquired pneumonia (CAP) antibiotic treatment started on admission with a composite measure of clinical deterioration and in-hospital mortality among a large sample of patients hospitalized in the US for nonsevere COVID-19.

The cohort included 520,405 patients with COVID-19; 51.2% of the population were men, and the median age was 66 years. The study included 17.8% Black patients, 12.2% Hispanic patients, and 58.5% White patients. There were 53.7% patients with Medicare insurance.

A total of 30.8% were treated with a CAP antibiotic regimen on day 1 of admission. The average length of hospital stay was 4 days and 7.9% of patients were readmitted to the same hospital within 30 days. The CAP treatment group used several diagnostic tests and COVID-19 treatments on day 1 substantially more often, including blood culture, lactate, procalcitonin, remdesivir, and systemic steroids. Patients treated with antibiotics were more likely to be admitted to hospitals with fewer than 400 beds, hospitals in the South and West, rural hospitals, and nonteaching hospitals.

The primary composite outcome—in which deterioration was defined by use of a vasopressor, high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, intermediate care, or intensive care unit admission—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 (absolute standardized difference, 4.1%).

Patients who received CAP antibiotics had higher odds of poor clinical outcomes (propensity matched OR [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).

Potential residual confounding despite robust methods and the absence of key physiologic and outpatient comorbidity data are among this study's limitations. Relying on administrative data for COVID-19 diagnosis and lacking a prespecified protocol with a post hoc outcome modification also limit the findings.

“Given the known risks from unnecessary antibiotic treatment, antibiotic stewardship strategies for promoting appropriate antibiotic use among patients admitted with nonsevere COVID-19 are needed,” study authors concluded.

References

1. Pulia MS, Griffin M, Schwei R, et al. Antibiotic treatment in patients hospitalized for nonsevere COVID-19. JAMA Netw Open. 2025;8(5):e2511499. doi:10.1001/jamanetworkopen.2025.11499

2. Antimicrobial resistance. World Health Organization. November 21, 2023. Accessed May 19, 2025. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

3. Koh SWC, Low SH, Goh JC, Hsu LY. Increase in antibiotic utilisation in primary care post COVID-19 pandemic. Antibiotics (Basel). 2025;14(3):309. doi:10.3390/antibiotics14030309