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Objective: To verify the effects of comprehensive infection prevention and control (IPC) interventions for the prevention of the cross-transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) within intensive care units (ICUs) in an epidemic region.Methods: A historical control, quasi-experimental design was performed. The study was conducted between January 2017 and December 2019, following the implementation of a multimodal IPC bundle. The baseline period was established from January 2013 to June 2013, when only basic IPC measures were applied.Results: A total of 748 patients were enrolled during the entire study. The incidence of ICU-acquired CRKP colonization/infection was 1.16 per 1,000 patient-days during the intervention period, compared with 10.19 per 1,000 patient-days during the baseline period (p = 0.002). The slope of the monthly incidence of CRKP at admission showed an increasing trend (p = 0.03). The incidence of ICU-acquired catheter-related bloodstream infections caused by CRKP decreased from 2.54 to 0.96 per 1,000 central-line-days (p = 0.08). Compliance with contact precautions and terminal room disinfection improved during the intervention period. All environmental surface culture samples acquired after terminal room disinfection were negative for CRKP.Conclusion: Our findings suggest that in epidemic settings, multimodal IPC intervention strategies and consistent monitoring of compliance, may limit the spread of CRKP in ICUs.