BackgroundCarbapenemase-producing Enterobacterales (CPE) poses a significant challenge to infection control in healthcare settings. Active screening is recommended to prevent intra-hospital CPE transmission.MethodsCPE screening was initiated at a 660-bed hospital in South Korea in September 2018, targeting patients previously colonized/infected or admitted to outside healthcare facilities (HCFs) within 1 month. Universal intensive care unit (ICU) screening was performed at the time of admission. After a hospital-wide CPE outbreak in July-September 2019, the screening program was enhanced by extending the indications (admission to any HCF within 6 months, receipt of hemodialysis) with weekly screening of ICU patients. The initial screening method was changed from screening cultures to the Xpert Carba-R assay. The impact was assessed by comparing the CPE incidence per 1000 admissions before (phase 1, September 2018-August 2019) and after instituting the enhanced screening program (phase 2, September 2019-December 2020).ResultsA total of 13,962 (2,149 and 11,813 in each phase) were screened as indicated, among 49,490 inpatients, and monthly screening compliance increased from 18.3 to 93.5%. Compared to phase 1, the incidence of screening positive patients increased from 1.2 to 2.3 per 1,000 admissions (P= 0.005) during phase 2. The incidence of newly detected CPE patients was similar (3.1 vs. 3.4,P= 0.613) between two phases, but the incidence of hospital-onset CPE patients decreased (1.9 vs. 1.1,P= 0.018). A significant decrease was observed (0.5 to 0.1,P= 0.014) in the incidence of patients who first confirmed CPE positive through clinical cultures without a preceding positive screening. Compared to phase 1, the median exposure duration and number of CPE contacts were also markedly reduced in phase 2: 10.8 days vs. 1 day (P< 0.001) and 11 contacts vs. 1 contact (P< 0.001), respectively. During phase 2, 42 additional patients were identified by extending the admission screening indications (n = 30) and weekly in-ICU screening (n = 12).ConclusionsThe enhanced screening program enabled us to identify previously unrecognized CPE patients in a rapid manner and curtailed a hospital-wide CPE outbreak. As CPE prevalence increases, risk factors for CPE colonization can broaden, and hospital prevention strategies should be tailored to the changing local CPE epidemiology.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13756-023-01270-8.