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Introduction: This study was conducted in response to the rising incidence of drug resistance observed in the intensive care unit (ICU) of King Fahad Medical City. Methodology: A retrospective observational study was conducted in the ICU of King Fahad Medical City between October 2003 and April 2012. Data were collected using a structured data sheet. Results: Nine episodes of infection with colistin-resistant Enterobacteriacae were recorded in seven patients. Five were females with an average age of 59.75 years. All patients had multiple co-morbidities; five had diabetes mellitus. In five of the episodes, Klebsiella pneumoniae was responsible, Serratia marcescens was reported in two, while Enterobacter aerogenes and Providencia stuartii were responsible for one episode of infection each. Prior colistin use was documented in all but one patient. Colistin resistance was defined by a minimum inhibitory concentration (MIC) of > 4 µg/mL according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint for Enterobacteriacae. Various antibiotics were used to treat the patients, with mortality reported in two. Conclusion: Infection due to colistin-resistant Enterobacteriacae is a rising challenge in Saudi Arabia; colistin use is thought to be associated with these infections. This calls for a stricter antimicrobial stewardship program and improved infection control measures to curb the rising trend of antibiotic resistance.