We compared the individual-level risk of hospital-onset infections with multidrug-resistant organisms (MDROs) in hospitalized patients prior to and during the coronavirus disease 2019 (COVID-19) pandemic. We also quantified the effects of COVID-19 diagnoses and intrahospital COVID-19 burden on subsequent MDRO infection risk.

Multicenter, retrospective, cohort study.

Patient admission and clinical data were collected from 4 hospitals in the St. Louis area.

Data were collected for patients admitted between January 2017 and August 2020, discharged no later than September 2020, and hospitalized ≥48 hours.

Mixed-effects logistic regression models were fit to the data to estimate patients’ individual-level risk of infection with MDRO pathogens of interest during hospitalization. Adjusted odds ratios were derived from regression models to quantify the effects of the COVID-19 period, COVID-19 diagnosis, and hospital-level COVID-19 burden on individual-level hospital-onset MDRO infection probabilities.

We calculated adjusted odds ratios for COVID-19–era hospital-onset Acinetobacter spp., P. aeruginosa and Enterobacteriaceae spp infections. Probabilities increased 2.64 (95% confidence interval [CI], 1.22–5.73) times, 1.44 (95% CI, 1.03–2.02) times, and 1.25 (95% CI, 1.00–1.58) times relative to the prepandemic period, respectively. COVID-19 patients were 4.18 (95% CI, 1.98–8.81) times more likely to acquire hospital-onset MDRO S. aureus infections.

Our results support the growing body of evidence indicating that the COVID-19 pandemic has increased hospital-onset MDRO infections.