Monitoring antibiotic use and bacterial resistance is a key component of programs aimed at preventing infections and antibiotic resistance. The objective of this study was to describe antibiotic use and bacterial resistance (Enterobacteriaceae producing extended-spectrum beta-lactamases—ESBL—or carbapenemases –EPC–, and methicillin-resistant Staphylococcus aureus –MRSA–) in healthcare facilities (HCFs) participating in the national Spares surveillance network each year during the 2019–2022 period. The use of systemic antibiotics (class J01 of the Anatomical Therapeutic Chemical (ATC) classification, rifampicin, oral imidazoles, and fidaxomicin), dispensed during inpatient stays, were expressed as the number of defined daily doses (DDD, ATC-DDD system, 2023) and reported relative to activity in terms of the number of hospital days (HD) in 1,217 HC participating each year. The incidence density (number of strains per 1,000 HD) was calculated for EBLSE, EPC, and MRSA in 472, 435, and 472 healthcare facilities, respectively. Antibiotic consumption was higher in 2022 than in 2019 (295 and 290 DDD/1,000 HD, respectively), particularly for broad-spectrum antibiotics, with the exception of fluoroquinolones. The incidence rate of EBLSE remained generally stable (0.55/1,000 hospital days in 2022); the incidence of EPCs had increased, particularly between 2021 and 2022 (0.024 per 1,000 person-days in 2022), and that of MRSA had decreased (0.15 per 1,000 person-days in 2022). These contrasting results underscore the need to continue these efforts, by integrating surveillance, prevention, and promotion of the appropriate use of antibiotics even more closely, as outlined in the new Spares 2023–2028 mandate.