antibiotics and healthcare-associated infections in outpatient care and the medical-social sector. The 2021 national data on antibiotic resistance in outpatient settings and nursing homes focus on three bacterial species of interest (Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus). Method: From January 1 to December 31, 2021, susceptibility testing results for E. coli, K. pneumoniae, and S. aureus isolated from diagnostic specimens were collected from a network of 1,564 clinical laboratories (LBM) spread across the 13 regions of mainland France as well as the islands of Guadeloupe and Martinique. The Spares initiative collected susceptibility testing data from long-term care facilities and healthcare institutions. Antibiogram data for strains isolated from patients living at home or nursing home residents were included in the analysis. Screening samples and samples from healthcare facilities were excluded. Antibiotic resistance was compared between C3G-susceptible and C3G-resistant strains. The proportions of pan-susceptible strains and strains resistant to one or more antibiotics (multidrug-resistant bacteria) were calculated. Statistical analyses were performed using Student’s t-test or analysis of variance. Results: In 2021, 715,938 susceptibility test results for Enterobacteriaceae strains isolated from urine samples were collected by the Primo and Spares initiatives (of which 85.9% were E. coli and 9.3% were K. pneumoniae). Among patients living at home, 3.2% of isolated E. coli strains were resistant to third-generation cephalosporins (C3G) and 2.8% produced extended-spectrum beta-lactamases (ESBLs). Among nursing home residents, resistance to 3G was observed in 9.2% of E. coli strains, and 8.4% were ESBL-producing. Resistance to fluoroquinolones (FQ) in E. coli was 12.7% for strains isolated from community-dwelling patients and 19.5% for those isolated from nursing home residents. In K. pneumoniae, ESBL production was observed in 8.3% of strains isolated from home-dwelling patients and 18.6% of those isolated from nursing home residents, while 12.5% of strains were resistant to FQs among home-dwelling patients and 23.3% among nursing home residents. Fifty-two strains of E. coli and 51 strains of K. pneumoniae produced a carbapenemase in home-dwelling patients, and 3 strains in nursing home residents for both species. For S. aureus, 7.6% of strains isolated from patients living at home (excluding urine samples) were methicillin-resistant, and 31.1% in nursing homes. Conclusion: Since 2017, the percentage of urinary E. coli strains producing ESBL has stabilized in outpatient care. Despite the low number of carbapenemase-producing Enterobacteriaceae isolated from diagnostic specimens in outpatient care and nursing homes in 2021, their increase warrants monitoring. Resistance to fluoroquinolones was increasing in community settings and nursing homes. Both fosfomycin and nitrofurantoin remained effective against E. coli strains in both settings.