Background The COVID-19 pandemic led to major disruptions in healthcare services at the hospital and community levels. The resulting impact on antibiotic resistance (ABR) in hospitals is difficult to predict. Methods We exploited data from the French national surveillance system over four years (2019-2022) including 414 hospitals across 12 French regions. We evaluated changes in annual antibiotic use compared to 2019 using multiple comparison tests. We also compiled a large dataset of 692,551 incident isolates for five antibiotic-bacterium pairs. Using negative binomial regression models accounting for autocorrelation and antibiotic use, we evaluated associations between resistant isolates incidence and COVID-19 indicators (pandemic periods or intubated COVID-19 patient prevalence). We investigated how these associations varied specifically in ICUs (n=85) and across geographical regions. Findings The use of some antibiotics, including azithromycin, imipenem and meropenem, significantly increased between 2020 and 2022. Concomitantly, the incidence of methicillin-resistant Staphylococcus aureus (up to 37%, 95% CI: 18-53%) and ESBL-producing Escherichia coli (up to 33%, 95% CI: 16-46%) isolates significantly decreased in hospitals and ICUs during the pandemic. A transient decrease in ICUs was also observed for ESBL-producing Klebsiella pneumoniae during periods of strong anti-COVID-19 interventions in the community (24%, 95% CI: 6-38%). No significant changes for ESBL-producing Enterobacter cloacae complex were observed. Very interestingly, the incidence of carbapenem-resistant Pseudomonas aeruginosa isolates was associated with COVID-19 intubation prevalence in hospitals (p<0.001) and ICUs (p<0.001), notably in the regions most affected by the pandemic. Interpretation Our results highlight strong modifications of antibiotic use and pathogen-specific global impacts of the COVID-19 pandemic on ABR in hospitals. Even though the biological mechanisms underlying between-species differences remain unclear, these results provide important insights into the potential impacts of a viral pandemic on ABR and support the need for pandemic preparedness in healthcare facilities. Funding ANR-10-LABX-62-IBEID.
