Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from blood and the related risk factors for infection in patients. Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae (KP) were isolated during hospitalization period in a hospital from January 2018 to December 2021 were retrospectively analyzed. Patients were divided into CRKP group (n=114) and non-CRKP group (n=269) based on antimicrobial resistance. According to the prognosis, 114 patients in the CRKP group were subdivided into the death group (n=30) and the survival group (n=84). General information, underlying diseases, antimicrobial use, and infection outcomes of two groups of patients were compared, and risk factors for infection and death after infection were analyzed. Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends, with statistically significant differences (both P=0.008). The CRKP group had higher resistance rates to amikacin, aztreonam, compound sulfamethoxazole, ciprofloxacin, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, tigecycline, ceftazidime, tobramycin, and levofloxacin, as well as higher in-hospital mortality than the non-CRKP group, with statistically significant differences (all P < 0.05). Acute pancreatitis prior to infection (OR=16.564, P < 0.001), hypoalbuminemia (OR=8.588, P < 0.001), stay in intensive care unit prior to infection (OR=2.733, P=0.017), blood transfusion (OR=3.968, P=0.001), bronchoscopy (OR=5.194, P=0.014), surgery within 30 days prior to infection (OR=2.603, P=0.010), and treatment with carbapenems (OR=2.663, P=0.011) were independent risk factors for the development of CRKP bloodstream infection (BSI). Cardiac insufficiency before infection (OR=11.094, P=0.001), combined with pulmonary infection (OR=20.801, P=0.010), septic shock (OR=9.783, P=0.002), disturbance of consciousness (OR=11.648, P=0.001), and receiving glucocorticoid treatment (OR=5.333, P=0.018) were independent risk factors for mortality in patients with CRKP BSI. Conclusion The resistance rate of KP from BSI to tigecycline and compound sulfamethoxazole presents upward trend. Underlying diseases, invasive procedures, and carbapenem treatment are closely related to CRKP BSI. Cardiac insufficiency, pulmonary infection, septic shock, disturbance of consciousness, and glucocorticoid treatment can lead to death of patients with CRKP BSI.