Antibiotic Use and Bacterial Infection Among Inpatients in the First Wave of COVID-19: A Retrospective Cohort Study of 64,691 Patients

Background: Hospitalized patients with SARS-CoV-2 infection (COVID-19) often receive antibiotics for suspected bacterial co-infection. We estimated the incidence of bacterial co-infection and secondary infection in COVID-19 using clinical diagnoses to determine how frequently antibiotics are administered when bacterial infection is absent. Methods: We performed a retrospective cohort study of inpatients with COVID-19 present on admission to hospitals in the Premier Healthcare Database between April – June 2020. Bacterial infections were defined using ICD-10-CM diagnosis codes and associated “present on admission” coding. Co-infections were defined by bacterial infection present on admission, while secondary infections were defined by bacterial infection that developed after admission. Co-infection and secondary infection were not mutually exclusive. Results: 18.5% of 64,961 COVID-19 patients (n=12,040) presented with bacterial infection at admission, 3.8% (n=2,506) developed secondary infection after admission, and 0.9% (n=574) had both. 76.3% (n=49,551) received an antibiotic while hospitalized, including 71% of patients who had no diagnosis of bacterial infection. Secondary bacterial infection occurred in 5.7% patients receiving steroids in the first 2 days of hospitalization, 9.9% receiving tocilizumab in the first 2 days of hospitalization, and 10.3% patients receiving both. After adjusting for patient and hospital characteristics, bacterial co-infection (aRR 1.15; 95% CI, 1.11 – 1.20) and secondary infection (aRR 1.93; 95% CI, 1.82 – 2.04) were both independently associated with increased mortality. Conclusions: Though 1 in 5 inpatients with COVID-19 present with bacterial infection, secondary infections in the hospital are uncommon. Most inpatients with COVID-19 receive antibiotic therapy, including 71% of those not diagnosed with bacterial infection.