Abstract Background The spread of Carbapenem-resistant Enterobacterales (CRE) continue to be a public health threat. Tennessee has participated in the Multidrug-Resistant Gram-Negative Bacilli Surveillance Initiative (MuGSI) since 2014. We investigated our data to describe the trends of CRE and CP-CRE and their changes during the COVID-19 outbreak. Methods Population-based surveillance targeting selected CRE organisms was conducted in Davidson County and seven surrounding counties in Tennessee. A CRE case was defined as isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a normally sterile body site or urine, in a surveillance area resident. A case was identified as incident if it was reported for the first time in the surveillance year or was a subsequent report of a case ≥30 days after the last report. The Tennessee state public health laboratory tests for carbapenemase production on CRE isolates received from clinical laboratories. The data analysis was conducted using SAS software version 9.4. Results 474 incident CRE cases were reported from 2016 to 2021. Females made up 68.63% and the average age was 65 years for both sexes. The incidence rate of CRE cases increased throughout study period and the rate in 2021 was 1.8-fold of 2016 (lowest rate for the study period) (P-value< 0.001). The incidence rate of CP-CRE increased in 2017 and 2018 compared to 2016 (p-value=0.01). The incidence rate for CP-CRE declined to the lowest level in 2020 (0.3 per 100,000 population). In 2021, the CP-CRE rate significantly increased compared to 2020 (p-value=0.02). The carbapenemase production (CP) positivity rate was also significantly higher in 2017(28.8%), 2018 (26.6%), and 2021 (25.8%) compared to the year 2020 where the positivity rate was the lowest (10.0%) (P-value< 0.05). Conclusion The transmission of CP-CRE cases decreased during the years prior to the COVID-19 outbreak despite the steady increase in CRE cases. The transmission of CP-CRE gained momentum during the COVID outbreak as evidenced by an increased infection rate and CP positivity rate in 2021. Renewed focus on implementing coordinated infection prevention strategies is likely to contribute to reducing the spread of antimicrobial-resistant pathogens. Disclosures All Authors: No reported disclosures.