The association between the COVID-19 pandemic and the incidence of invasive infections caused by multidrug-resistant organisms remains a topic of debate. To analyse the national incidence rates of bloodstream infections (BSI) caused by Escherichia coli (EC) and Klebsiella pneumoniae (KP) with extended-spectrum cephalosporin-resistance (ESCR) in two distinct regions in Switzerland, each exhibiting varying antimicrobial resistance patterns and that were impacted differently by the pandemic. We analysed data of positive blood cultures prospectively collected by the nationwide surveillance system (ANRESIS) from January 1, 2015, to August 31, 2022. To explore the potential relationship between COVID-19 patient occupancy and ESCR incidence rates, we conducted an in-depth analysis over the two-year pandemic period from April 1, 2020, to March 30, 2022. We employed Quasi-Poisson and logistic regression analyses to investigate these associations. During the study period, a total of 40997 EC-BSI and 8537 KP-BSI episodes were collected and reported to ANRESIS by the participating hospitals. ESCR was observed in 11% (n=4313) of E. coli and 8% (n=664) of K. pneumoniae, respectively. A significant reduction in ESCR-EC BSI incidence occurred during the pandemic in the region with the highest COVID-19 incidence. Conversely, ESCR-KP BSI incidence initially fell considerably and then increased during the pandemic in both regions, however, this effect was not statistically significant. No association between hospital occupancy from COVID-19 patients and these trends was observed. In the early phase of the COVID-19 pandemic, a decrease in ESCR rates was observed, particularly in ESCR-EC BSI within the most heavily impacted region.