Patients hospitalized with nonsevere COVID-19 infections who received empiric antibiotics targeting community-acquired pneumonia may not experience clinically meaningful improvement in outcomes and could have a slightly increased risk of clinical deterioration or in-hospital mortality.
In the retrospective cohort study, investigators used a target trial emulation design to analyze data from the Premier Healthcare Database, which includes a large proportion of inpatient admissions from acute care hospitals across the United States. The investigators included 520,405 immunocompetent adult patients admitted to general care for COVID-19 infections between April 2020 and December 2023 at 1,053 hospitals. Patients with nonpneumonia bacterial infections, chronic obstructive pulmonary disease exacerbations, and immunosuppression were excluded. The investigators defined exposure as receipt of a community-acquired pneumonia (CAP) antibiotic regimen on the first day of hospitalization.
The primary outcome was a composite of clinical deterioration or in-hospital mortality beginning on the second day of hospitalization or later. Clinical deterioration included intensive care unit (ICU) admission, vasopressor use, receipt of high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or transfer to intermediate care. Secondary outcomes included hospital length of stay and 30-day all-cause readmission. Adverse antibiotic outcomes included kidney failure, allergic reactions, and Clostridioides difficile infection.
Among the full cohort, nearly 31% of the patients received the CAP antibiotic regimen on their first hospital day. The primary composite outcome occurred among about 21% of the patients treated with antibiotics compared with 18% of those who didn't receive antibiotics. In propensity-matched analyses, antibiotic treatment remained associated with a slightly higher risk of clinical deterioration or mortality. Similar findings were observed in inverse probability treatment weighted and standardized mortality ratio weighted analyses.
In-hospital mortality occurred in about 5% of the patients who received antibiotics compared with 4% of the patients who didn't receive antibiotics. Rates of ICU admission, invasive mechanical ventilation, noninvasive ventilation, and vasopressor use were also numerically higher in the antibiotic treatment group. Median hospital length of stay was longer among the patients treated with antibiotics, while 30-day readmission rates were slightly higher among those who didn't receive antibiotics. The investigators didn't observe meaningful differences in kidney failure, allergic reactions, or C difficile infection.
The investigators also evaluated a subgroup of 33,617 patients with available procalcitonin results at admission. Elevated procalcitonin levels didn't identify a subgroup that appeared to benefit from empiric antibiotics, and they found no statistically significant interaction between procalcitonin status and antibiotic treatment.
The investigators noted several limitations, including the observational design and the possibility of residual confounding despite extensive propensity matching and adjustment. The database didn't include physiologic measures such as oxygen saturation or respiratory rate, limiting adjustment for disease severity at presentation. The investigators also relied on administrative coding to identify diagnoses, comorbidities, and outcomes.
The findings may have added to evidence suggesting low rates of confirmed bacterial coinfection in patients hospitalized with COVID-19 infections, despite ongoing empiric antibiotic prescribing.
“Given the known risks from unnecessary antibiotic treatment, antibiotic stewardship strategies for promoting appropriate antibiotic use among patients admitted with nonsevere COVID-19 [infections] are needed,” wrote lead study author Michael S. Pulia, MD, PhD, of the BerbeeWalsh Department of Emergency Medicine at the University of Wisconsin-Madison School of Medicine and Public Health, and colleagues.
The study was funded by the Agency for Healthcare Research and Quality. Co–study author Lucas T. Schulz, PharmD, reported employment with Cepheid outside the submitted work, and co–study author Penelope Pekow, PhD, reported grants from the National Institutes of Health during the conduct of the study. The study authors reported no other conflicts of interest.
Source: JAMA Network Open
