Abstract Background The CRE epidemic in Colombia is amplified by horizontal transmission of mobile genetic elements encoding KPC among Enterobacteriaeae and clonal expansion of K. pneumoniae clonal group (CG) 258, making the country hyperendemic for CRE. However, the clinical impact of CRE infections has not been comprehensively assessed. Methods In the framework of a prospective study assessing the clinical epidemiology of CRE (CRACKLE II), we report the results of the first 246 patients enrolled in 5 Colombian hospitals (from July 2017 to November 2018). Clinical variables, outcomes at 90 days post-hospitalization and susceptibility patterns were collected. Resistance to carbapenems was defined per CDC guidelines. Infection was defined with standardized criteria. All isolates which did not meet these criteria were considered colonization Results The majority of patients were men (66%); median age was 62 years [IQR 37–73]); 67% were admitted from home and 33% were hospital transfers. The mean Charlson Comorbidity Index and Pitt Bacteremia scores were 2 (SD = 2) and 3 (SD = 3), respectively. Most patients (60%; n = 148) were considered to be infected. The most frequent source of culture was urine (36%), followed by blood (30%) and wound secretions (13%). A respiratory source was found in the minority (6%) of patients. Species of CRE are summarized in Table 1 with the majority being K. pneumoniae. The best in vitro activity against CRE was found for fosfomycin (80% susceptible (47/59)), tigecycline (75% (67/89)), colistin (70% (35/50)) and amikacin (67% (148/220)). From 234 patients with available information at 90 days of follow-up, 13% were readmitted after discharge. Mortality at 30 and 90 days after a positive culture was 31% and 35%, respectively. Conclusion K. pneumoniae are the main drivers of the CRE epidemic in Colombia isolated mainly from non-respiratory sources. Non-susceptibility to last resource antibiotics (tigecycline, colistin and fosfomycin) is substantial among the Colombian isolates leaving few therapeutic options, a finding that correlates with high mortality. Our findings indicate that introduction of novel therapeutics in Colombia is urgently needed with a rampant epidemic of CRE causing high burden of disease. Disclosures All authors: No reported disclosures.