A large cohort study by researchers at the University of Wisconsin School of Medicine and Public Health, published in JAMA Network Open, offers the best evidence to date that routinely prescribing antibiotics to hospitalized COVID-19 patients may cause more harm than good.
Led by Dr. Michael Pulia, associate professor of emergency medicine and director of the Emergency Care for Infectious Diseases research program, the study of more than 520,000 adults hospitalized with COVID-19 between April 2020 and December 2023 showed that patients who received antibiotics were at a slightly higher risk for negative health outcomes than those who did not.
The study team used a target trial emulation design to analyze data from 1,053 U.S. hospitals that contribute de-identified data to the Premier Healthcare Database.
Although COVID-19 is a viral illness and antibiotics are ineffective, about 31% of patients observed received antibiotics on their first hospital day, mainly due to concerns about possible bacterial pneumonia — a rare complication. The study found that 21% of patients given antibiotics either died or experienced worsening health, compared to 18% who did not receive antibiotics. Patients with immune deficiencies, chronic lung disease, confirmed bacterial infections, or critical illness were excluded from the study.
According to Pulia, the findings emphasize the potential risks of unnecessary antibiotic use, including disruption of healthy bacteria, weakened immunity, and detrimental side effects.
The study team also found that procalcitonin, a blood test often used by doctors in cases where a bacterial infection is suspected, was not associated with antibiotic prescribing, potentially indicating a lack of clinical utility for patients with COVID-19.
“We hope our data will help guide clinician decision-making by demonstrating that routine antibiotic use in this population does not seem to offer any benefit and may even pose risks, particularly given the urgent public health threat of antibiotic resistance,” Pulia said.
An accompanying editorial from Australian infectious disease experts commended the research for its large sample size and its value in guiding clinical decision-making when randomized trials are unavailable.
The study authors conclude that antibiotics should not be used routinely in hospitalized COVID-19 patients unless there is clear evidence or high concern for bacterial infection, emphasizing the importance of targeted, evidence-based treatment to protect both individual and public health.
This article was adapted from a release by the UW School of Medicine and Public Health published on July 1, 2025.
Funding for this study was provided by the Agency for Healthcare Research and Quality R01 grant No. HS028669.