Abstract: OBJECTIVE To evaluate the attainment of therapeutic plasma concentrations of polymyxin B (PMB) at conventional clinical doses in the elderly critically ill patients, analyze the major influencing factors and explore the relationship between plasma concentration and clinical therapeutic effect so as to provide real-world evidence for the individualized use of PMB among the group of patients. METHODS The clinical data were retrospectively collected from the elderly patients with severe infection who were treated with PMB and were under monitoring of plasma concentration in The Third Hospital of Changsha from Jan. 2021 to Dec. 2025. The attainments of pharmacokinetics and pharmacodynamics (PK/PD) targets for PMB were analyzed. Multiple linear regression analysis was performed for the influencing factors for the plasma concentration of PMB, and the relationship between the plasma concentration of PMB and the clinical therapeutic effect was observed. RESULTS A total of 139 patients were enrolled in the study. The polymyxin B (PMB) trough concentration (C_min) ranged from 0.13 μg/ml to 3.98 μg/ml, and the average steady-state concentration (C_ss,avg) ranged from 0.48 μg/ml to 6.37 μg/ml. Set the C_ss,avg ranging between 2 and 4 μg/ml as the PK/PD target value, the attainment rate was 65.47%. The multiple linear regression analysis showed that the daily dose (P=0.044) was an independent influencing factor for the C_ss,avg of PMB, while creatinine (P=0.010), albumin (P=0.006), and 24-hour fluid intake (P=0.022) were independent influencing factors for the C_min of PMB. The clinical effective rate of the PMB C_ss,avg target attainment group was 57.14%, higher than 29.41% of the failed attainment group (χ²=4.420,P=0.036); the microbial eradication rate of the PMB C_ss,avg target attainment group was 43.96%, higher than 11.76% of the failed attainment group (χ²=6.250,P=0.012). CONCLUSIONS There are a variety of influencing factors for the low attainment rate of PK/PD of PMB among the elderly patients with severe infections. It is necessary to carry out the therapeutic drug monitoring (TDM) so as to optimize the administration of PMB for the elderly patients with severe infections and improve the clinical therapeutic effect.