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Objectives: This investigation was conducted to study co-colonization by carbapenem-resistant Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) and Acinetobacter baumannii (CRAB) in intensive care unit (ICU) patients in Palermo, Sicily, a geographic area where both organisms are endemic in the healthcare setting. Risk factors at admission and during ICU stay and outcomes were also evaluated., Methods: All patients colonized by KPC-Kp, or CRAB, or both in 2 ICUs of a large general hospital during the period October 2011-March 2012 were enrolled. Demographics and clinical data were collected. Resistance determinants and clonality of the 2 organisms were characterized by molecular methods., Results: Seventy-five of 391 patients (19.2%) proved to be colonized by KPC-Kp, CRAB, or both: 30 (40%) were co-colonized and 44 (58.7%) were mono-colonized by CRAB and 1 by KPC-Kp. Younger age, major trauma, and length of stay were positively associated with co-colonization. However, no significant differences were detected between co-colonized and non co-colonized patients in infection and ICU mortality rates and length of stay after the first isolation. Both organisms proved to be circulating in a clonal way., Conclusions: In our setting, co-colonization by KPC-Kp and CRAB disproportionately affected young trauma patients with those with a prolonged ICU stay.