Antimicrobial resistance poses a major threat to public health. There are few comprehensive nationwide studies that quantify long-term trends in infection incidence and antimicrobial resistance for multiple pathogens. We aimed to analyse trends in inpatient infection incidence and antimicrobial resistance for nine pathogens over the past 15 years across the USA.

In this US nationwide retrospective cohort study, we analysed clinical microbiology data from electronic health records from all patients admitted to all 138 Veterans Affairs (VA) Medical Centers with acute care wards across the USA from Feb 1, 2007, to March 31, 2022. We quantified inpatient antibiotic use as days of therapy (DOT) per 1000 patient-days and antimicrobial resistance by resistance proportion (proportion of incident isolates identified as resistant) and phenotypic incidence (incidence of infections per 1000 admissions classified as resistant, susceptible, or missing). To analyse trends before the COVID-19 pandemic and during the COVID-19 pandemic, we used generalised estimating equation models and reported average annual percentage changes (AAPC).

We collected 991 527 30-day incident isolates from 507 760 patients in 138 VA Medical Centers and 50 states in the USA. Between Feb 1, 2007, and Dec 31, 2019, infection incidence and antimicrobial resistance declined for many pathogens and pathogen–drug combinations. The proportion of methicillin resistance in Staphylococcus aureus decreased from 57·7% (11 876 of 20 584 incident isolates) to 44·6% (5916 of 13 257) over these 13 years (AAPC –1·8%; 95% CI –2·4 to –1·2; p<0·0001), and vancomycin-resistant Enterococcus faecium infections decreased from 77·8% (2555 of 3285) to 65·1% (893 of 1371; AAPC –1·2%; 95% CI –2·5 to 0·0; p=0·052). Fluoroquinolone resistance declined in both proportion and incidence for most pathogens. These trends correlated with substantial reductions in fluoroquinolone use, from 125 DOT per 1000 patient-days to 20 DOT per 1000 patient-days. Third generation cephalosporin resistance increased steeply in Escherichia coli infections from 6·7% (942 of 14 042) in 2007 to 15·3% (2153 of 14 053) in 2019 (AAPC 8·5%; 95% CI 6·2 to 10·7; p<0·0001). Carbapenem resistance proportion increased in Enterobacter cloacae infections from 1·1% (30 of 2852) in 2007 to 7·3% (212 of 2919) in 2019 (AAPC 19·8%; 95% CI 13·7 to 26·2; p<0·0001), but remained low for Klebsiella pneumoniae and E coli. During the COVID-19 pandemic between Jan 1, 2020, and March 31, 2022, several pathogen–drug combinations increased in both incidence and resistance for hospital-associated infections. For some pathogen–drug combinations, trends in incidence of resistant and susceptible infections were divergent, whereas for other combinations, these trends were in the same direction.

Significant reductions in methicillin resistance in S aureus, vancomycin-resistant E faecium, and fluoroquinolone resistance across multiple pathogens suggest that control efforts have had an effect on resistance. The rise in extended-spectrum β-lactamases-producing Enterobacterales and recent surge in hospital-associated infections emphasise the need for ongoing surveillance and interventions. Our study highlights how coupling the analysis of phenotypic incidence with resistance proportion can enhance interpretation of antimicrobial resistance data.

US Centers for Disease Control and Prevention.