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Purpose: The aim of this study was to assess the risk factors for colistin-resistant carbapenemase-producing Enterobacterales (CR-CPE), and describe the mortality associated with this organism, in a low-income country., Methods: A descriptive, observational, and prospective multicenter study was carried out in Guayaquil, Ecuador. All patients with carbapenem-resistant Enterobacterales admitted between December 2021 and May 2022 were enrolled. Infection definitions were established according to the Centers for Disease Control and Prevention (CDC) protocols. The presence of carbapenemase-producing Enterobacterales was confirmed with a multiplex PCR for bla KPC, bla NDM, bla OXA-48, bla VIM, and bla IMP genes. MCR-1 production was studied molecularly, and MLST assays were carried out., Results: Out of 114 patients enrolled in the study, 32 (28.07%) had at least one positive sample for CR-CPE. Klebsiella pneumoniae ST512-KPC-3 was the most frequent microorganism isolated. Parenteral feeding, β-lactamase inhibitor use, recent hemodialysis, and renal failure were all considered independent risk factors for carrying CR-CPE. A mortality of 41.22% was detected, but we could not find any difference between colistin-resistant and colistin-susceptible CPE. MCR-1 production was not detected in any of the isolates studied., Conclusion: A significant burden for CR-CPE was found in a South American country that was mainly caused by the high-risk clone K. pneumoniae ST512-KPC-3 and not mediated by mcr-1 production. Its acquisition involved parenteral feeding, β-lactamase inhibitor use, recent hemodialysis, and renal failure as independent risk factors, demonstrating the critical need for infection prevention and stewardship programs to avoid dissemination to other countries in the region., (© 2023. The Author(s).)