- Background This study examined predictors of carbapenem-resistant Klebsiella pneumoniae (CRKP) colonization and risk factors for the development of CRKP infection in patients initially only colonized with CRKP. Methods A total of 464 patients with CRKP rectal colonization (CRKP-RC) were identified. Two case-control studies were performed, one comparing risk factors for CRKP-RC in patients who did not develop CRKP infection (CRKP-IN) versus patients without CRKP-RC and CRKP-IN, and the other comparing CRKP-RC patients who did not develop CRKP-IN with those who did. Results Forty-two of the 464 colonized patients developed CRKP-IN. Multivariate analysis identified the following predictors for CRKP-RC: antibiotic therapy (odds ratio [OR], 5.76; P ≤ .0001), aminopenicillin therapy (OR, 7.753; P = .004), bedridden (OR, 3.09; P = .021), and nursing home residency (OR, 3.09; P = .013). Risk factors for CRKP-IN in initially CRKP-RC–positive patients were previous invasive procedure (OR, 5.737; P = .021), diabetes mellitus (OR, 4.362; P = .017), solid tumor (OR, 3.422; P = .025), tracheostomy (OR, 4.978; P = .042), urinary catheter insertion (OR, 4.696; P = .037), and antipseudomonal penicillin (OR, 23.09; P ≤ .0001). Conclusions We suggest that in patients with CRKP-RC, a strategy for preventing CRKP-IN might include limiting antipseudomonal penicillin and carbapenem use and preventing infections by closely following compliance with infection control bundles.