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Background: Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes. Methods: The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case–control study of surviving and non-surviving patients was conducted. Results: Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2–52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p = 0.015) and prolonged neutropenia (p = 0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p = 0.001 and p = 0.001, adjusted r2 = 0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p