Effects of COVID-19 on Antimicrobial Resistance in U.S. Hospitals
August 1, 2025 4 minutes read
By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Synopsis: In a retrospective cohort study, researchers found that antimicrobial-resistant (AMR) infections increased during the COVID-19 pandemic from 182 to 193 per 10,000 hospitalizations. Recent antibiotic exposure, increased illness severity, and comorbidities were associated with AMR infections.
Source: Yek C, Mancera AG, Diao G, et al; National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative. Impact of the COVID-19 pandemic on antibiotic resistant infection burden in U.S. hospitals: Retrospective cohort study of trends and risk factors. Ann Intern Med. 2025;178:796-807.
The COVID-19 pandemic has had a significant effect on the U.S. healthcare system. There is evidence that many patients hospitalized for COVID-19 received antibiotics unnecessarily. The overuse and misuse of antibiotics are the main drivers for the spread of antimicrobial resistance (AMR). Yek and colleagues sought to determine the effect of the COVID-19 pandemic on the spread of AMR within U.S. hospitals. They also aimed to identify factors that contributed to the incidence of AMR infections.
The study was a retrospective cohort analysis that included 243 U.S. hospitals. The researchers defined the prepandemic time as January 2018 to December 2019, the peak pandemic as March 2020 to February 2022, and the waning pandemic as March to December 2022. Cases were screened for cultures from any source for growth from Staphylococcus aureus, Enterococcus spp., Acinetobacter spp., Pseudomonas aeruginosa, or Enterobacterales. Resistance phenotypes were identified for methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococci (VRE), extended-spectrum cephalosporin-resistant Enterobacterales (ECR-E), carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant P. aeruginosa (CRPE), and carbapenem-resistant Acinetobacter (CRAB). The investigators classified infections as community-onset if the index culture was collected within three calendar days of admission. Patients were excluded who were younger than 18 years of age, were transferred from another hospital, or were outpatients.
There were 9,995,696 hospitalizations included in the study. Of these, 178,579 infection episodes were associated with one of the six AMR phenotypes. The most common phenotype was MRSA (40.6%), followed by ECR-E (38%). The incidence of AMR was greater among large, urban teaching hospitals, while antibiotic prescribing was higher in rural hospitals in the South and West.
The overall rate of AMR increased from 182 to 193 per 10,000 hospitalizations (6.5%; 95% confidence interval [CI], 5.1% to 8.0%) during the pandemic. Infections with hospital-onset that were caused by the pathogens of interest (regardless of resistance) had greater increases (31.6%; 95% CI, 29.4% to 33.8%) compared to infections of community-onset (0.8%; 95% CI, 0.1% to 1.5%) during the pandemic period. AMR bloodstream infections had proportionally greater increases (21.5%; 95% CI, 17.8% to 25.3%) compared to respiratory AMR infections (9.4%; 95% CI, 5.7% to 13.3%) and urinary AMR infections (8.7%; 95% CI, 6.2% to 11.3%). Notably, AMR skin and soft tissue infections decreased during the pandemic period (-6.4%; 95% CI, -8.8% to 3.9%). As the pandemic waned, community-onset AMR returned to the prepandemic baseline, but hospital-acquired AMR remained elevated at 11.6% (95% CI, 6.8% to 16.7%).
The largest increase in AMR infections was due to CRAB (45.7%; 95% CI, 30.8% to 62.3%). This was followed by CRE (25.1%; 95% CI, 16.4% to 34.3%), ECR-E (19.4%; 95% CI, 16.7% to 22.1%), CRPA (11.4%; 95% CI, 5.6% to 17.6%), and VRE (6.0%; 95% CI, 1.2% to 10.9%). Interestingly, MRSA infections decreased (-6.2%; 95% CI, -8.1% to -4.2%). As the pandemic waned, all of the Gram-negative hospital-onset resistant phenotypes remained above prepandemic baseline levels.
Several patient factors were associated with hospital-acquired AMR infections. These included age ≤ 77 years, male sex, admission from a non-home source, presence of medical comorbidities, presence of respiratory or neurological failure on admission, admission to the intensive care unit (ICU), vasopressors, recent antibiotic exposure, and mechanical ventilation. No hospital factors were associated with AMR infections during the pandemic. Furthermore, patients with COVID-19 had a higher probability of developing hospital-acquired AMR infections than patients without COVID-19.
Commentary
The incidence of AMR infections increased in U.S. hospitals during the COVID-19 pandemic, with hospital-onset Gram-negative infections remaining above their prepandemic baseline. This is an important and disconcerting finding. The increase was likely to have been at least partly driven by antibiotic overprescribing. Clinicians managing patients with respiratory failure from COVID-19 often faced diagnostic uncertainty about whether a concurrent bacterial respiratory infection was present. Often the default strategy was to prescribe empiric antibiotics. The study identified patient factors besides having COVID-19 that increased the risk for an infection due to an AMR pathogen. A greater awareness of these could be used to guide isolation practices and empiric antibiotic choices.
The study had some limitations. Because the investigators used diagnostic codes rather than physiological data, residual confounding could have affected the results. Also, culture positivity was used to define infections, but this may have captured colonization instead. Finally, because antibiotic prescribing and rates of AMR are different in U.S. hospitals compared to other countries, the results might not be generalizable on a global scale.
The COVID-19 pandemic saw an increase in AMR in U.S. hospitals that was associated with preexisting conditions and acute illness severity. Thus, efforts must continue to rebound from this setback and to learn lessons for when the next global pandemic strikes.
Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC, is Professor of Medicine, Division of Infectious Diseases, Northeast Ohio Medical University, Rootstown, OH.
In a retrospective cohort study, researchers found that antimicrobial-resistant (AMR) infections increased during the COVID-19 pandemic from 182 to 193 per 10,000 hospitalizations. Recent antibiotic exposure, increased illness severity, and comorbidities were associated with AMR infections.
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