Association of SARS-CoV-2 status and antimicrobial-resistant bacteria with inadequate empiric therapy in hospitalized patients: a US multicenter cohort evaluation (July 2019 - October 2021)

Background: Antibiotic usage and antimicrobial resistance (AMR) patterns changed during the COVID-19 pandemic. Inadequate empiric antibiotic therapy (IET) is a significant public health problem and contributes to AMR. We evaluated factors associated with IET before and during the COVID-19 pandemic to determine the impact of the pandemic on antibiotic management. Methods: This multicenter, retrospective cohort analysis included hospitalized US adults who had a positive bacterial culture (specified gram-positive or gram-negative bacteria) from July 2019 to October 2021 in the BD Insights Research Database. IET was defined as antibacterial therapy within 48 hours that was not active against the pathogen. AMR results were based on facility reports. Multivariate analysis was used to identify risk factors associated with IET in patients with any positive bacterial culture and AMR-positive cultures, including multidrug-resistant (MDR) pathogens. Results: : Of 278,344 eligible patients in 269 hospitals, 56,733 (20.4%) received IET; rates were higher in patients with AMR-positive (n=93,252) or MDR-positive (n=39,000) cultures (34.9% and 45.0%, respectively). Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients had significantly higher rates of IET (25.9%) compared with SARS-CoV-2-negative (20.3%) or not tested (19.7%) patients overall and in the AMR and MDR subgroups. Patients with AMR- or MDR-positive cultures had more days of therapy and longer lengths of stay. In multivariate analyses, AMR, MDR, SARS-CoV-2-positive status, respiratory source, and prior admissions were identified as key IET risk factors. Conclusions: : IET remained a persistent problem during the COVID-19 pandemic and occurred at higher rates in patients with AMR/MDR bacteria or a co-SARS-CoV-2 infection.