#329 Effectiveness of dosing strategies of polymyxin B among sepsis patients with and without renal replacement therapies

Abstract

Abstract Background and Aims Despite numerous population pharmacokinetic studies on polymyxin B, a gap exists in establishing uniform dosing strategies among sepsis patients due to various clinical and patient related factors. The International Consensus guidelines, provide detailed dosing calculation for colistin but not for polymyxin B in renal impairment patients [1]. We aimed to compare and evaluate the effect of various dosing strategies of both polymyxin B and colistin among sepsis patients with and without renal replacement therapies (RRT) in the clinical setting. Method We conducted a retrospective audit on adult patients (aged≥ 18 years) diagnosed with gram negative sepsis, both with and without RRT, who were administered polymyxins. Data was collected from the medical records of patients admitted to critical care setting of a tertiary care hospital from January 2018 to December 2022. Patients who received polymyxin B doses for less than 3 days, pediatric, neonate patients or those discharged against medical advice were excluded. Data such as demographic details, RRT, polymyxin type and dosage, and therapy outcomes were collected. Polymyxin B dosing strategies were converted into low dose group (LD) [≤100 mg >150 mg loading dose (ld) and <150 mg maintenance dose (md)], usual dose group (UD) [150 mg ld and 150 mg md] and high dose (HD) [150 mg ld and >150 mg md] to evaluate its effectiveness [2]. Linear and logistic regression were used for continuous and categorical outcomes respectively. All statistical analyses were performed using IBM SPSS vs 29.0 [3]. Results Our study cohort included 550 patients with mean age of 59.79 ± 15.78 years, and majority of them being male patients (55.2%). A total of 243 (39.6%) patients were on RRT. Among the study population, 465 (84.5%) patients were on polymyxin and 146 (26.5%) were on colistin therapy. Regression analysis of different regimens of Polymyxin B prescribed with various doses showed UD group (p = 0.04) as well as HD group (p = 0.05) with better outcome in terms of improvement. Among the Polymyxin B cohort patients on RRT, HD group showed better outcome (p = 0.045). There was a significant mean difference between polymyxin B dosing strategies with respect to ventilator-free days (p = 0.006), while the other clinical outcomes showed non-significant results. Conclusion Our results suggest polymyxin B dosing strategy with a loading and maintenance dose of 150 mg in general patients. In patients with RRT, a loading dose of 150 mg and maintenance dose of >150 mg is warranted. Further population pharmacokinetic studies with large sample size of RRT patients on polymyxin B is required.