Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

亚治疗剂量、较短的治疗疗程、女性性别、菌血症以及肾功能损害，均为多粘菌素B（polymyxin B）治疗失败的独立预测因素。本研究发现，多粘菌素B不恰当剂量（<15000或>25000单位/公斤/天）与肾功能损害存在显著关联。多粘菌素B不恰当剂量与肌酐清除率（creatinine clearance, CrCl）20~50 mL/min（p=0.021，校正比值比（adjusted odds ratio, ORadj）6.660，95%置信区间（95% confidence interval, 95% CI）1.326~33.453）以及CrCl<20 mL/min（p=0.001，ORadj 22.200，95% CI 3.481~141.592）均存在显著相关性。仅纳入剂量恰当的研究对象开展亚组分析后可见，肾功能损害与多粘菌素B治疗失败不再存在关联，由此提示治疗失败的原因在于多粘菌素B剂量不恰当，而非肾功能损害。综上，肾功能损害并非直接与治疗失败相关，而是因肾功能调整后多粘菌素B剂量不恰当所致。