The COVID-19 pandemic placed pressure on healthcare systems and led to expanded and empirical use of antibiotics, despite being a viral infection. Fear of coinfections, lack of microbiological diagnosis, and off-protocol use of drugs such as azithromycin and ceftriaxone contributed to this increase. This study evaluates the pattern of hospital antibiotic prescriptions within the Brazilian Unified Health System (SUS) during the pandemic and its implications for antimicrobial resistance.

Ecological, descriptive study based on data from the SUS Hospital Information System (SIH/SUS) and the Health Price Database (BPS). Hospitalizations with recorded administration of systemic antibacterials (ATC code J01) between January 2019 and December 2023 were included. Data were aggregated by year, geographic region, and active substance. Frequency of use, average cost per hospitalization, and temporal trends were evaluated. Antibiotics showing the greatest growth were identified and compared across Brazil’s five regions.

Between 2019 and 2023, there was a significant increase in hospital antibiotic use in Brazil, peaking in 2021. In 2020, ceftriaxone use rose 35% compared with 2019, while azithromycin increased by 120%, especially in field hospitals and emergency units. The average cost per hospitalization involving antibiotics rose from R$ 4,200 in 2019 to R$ 6,150 in 2021. In 2022 and 2023, usage stabilized but did not return to pre-pandemic levels. The Southeast and Northeast regions accounted for 65% of total hospital antibiotic consumption during the period evaluated.

The increase in antibiotic use during the COVID-19 pandemic in Brazil reflected clinical uncertainty and the adoption of non-evidence-based practices, with frequent empirical prescriptions lacking bacterial coinfection confirmation. This scenario contributed to the risk of antimicrobial resistance, worsened by persistently high consumption even after the acute pandemic phase. Regional disparities indicate differences in protocol adherence and diagnostic access. Therefore, there is an urgent need for rational use programs, stewardship strategies, team training, and expansion of access to microbiological testing.