ABSTRACT Polymyxin B is one of the last resort option for carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection in China. Therefore, the timing of administration of polymyxin is frequently delayed. We collected 40 cases of CRKP bloodstream infections (BSIs) treated with combinations based on polymyxin B over 30 months. The primary outcome, 30-day mortality rate, was 52.5% (21/40). Early administration of polymyxin B is meant to administer the drug within 48 h of diagnosing bacteremia. Delayed administration was considered when polymyxin B was administered after 48 h of bacteremia onset. Polymyxin B duration and total dosages were similar in the two groups (11.57 days versus 11.76 days, p = 0.919; 1306.52 mg versus 1247.06 mg, p = 0.711). Compared with delayed administration, early use of polymyxin B-based combination therapy had a significant increase in the rate of bacterial clearance (65.22% versus 29.41%, p = 0.025; OR = 0.533) and decreased 30-day mortality (39.13% versus 70.59%, p = 0.045; OR = 0.461) and overall mortality (43.48% versus 82.35%, p = 0.022; OR = 0.321).