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Objectives: To describe the treatment and outcomes of patients with carbapenemase-producing Enterobacteriaceae and evaluate whether these cases represented active infection requiring antibiotic therapy or colonization. Methods: Adult inpatients with carbapenemase-producing Enterobacteriaceae were retrospectively evaluated. Cases were classified as colonization versus infection by 2 infectious diseases physicians. Multiple cultures that grew in the same patient within a 2-week period were evaluated as a single case. Results: A total of 42 cases among 35 patients were identified. The mean age of the cohort was 67.7 ± 13.7 y, mean APACHE II score was 17.9 ± 8.6, and 77% of patients were in the intensive care unit when the carbapenem-producing Enterobacteriaceae was isolated. Klebsiella pneumoniae (84%) was the predominant organism; urine (36%), tissue/wound/drainage (25%), and blood (20%) were the most common sites of collection. Though 43% of cases were classified as colonization, 56% of these cases were treated with antibiotics. Only 1 patient characterized as colonized subsequently developed infection, 29 days later. Among infected cases, colistin (55%), meropenem (41%), aminoglycosides (32%), and tigecycline (27%) were used for treatment, and combination antimicrobial therapy was common (55%). Clinical and microbiological success was higher in patients receiving combination therapy (83% vs 60%, p == 0.35). Colistin monotherapy was only successful in urinary infections. All-cause hospital mortality was 29%. Conclusions: Nearly half of cases represented colonization, yet the majority were treated with broad-spectrum antibiotics. Determining infection versus colonization is a critical first step in managing patients with carbapenemase-producing Enterobacteriaceae. The risk of not treating apparent colonization appears low. [ABSTRACT FROM AUTHOR]