重症感染患者替考拉宁血药浓度影响因素探讨

Study on the influencing factors of blood drug concentration of teicoplanin in patients with severe infections

目的监测重症感染患者替考拉宁起始负荷剂量治疗第2天的血药谷浓度(C_(min))及目标浓度(C_(min)≥10mg/L)达标情况,探讨早期血药谷浓度的影响因素。方法对2018年3月—2019年3月重症医学科38例使用替考拉宁治疗的重症感染患者进行回顾性分析,根据起始负荷剂量分为高剂量组(≥10mg/kg)和低剂量组(<10mg/kg),均间隔12h静脉注射3剂,于第3剂前30min采集血样,应用高效液相色谱法(HPLC)测量C_(min)。分析替考拉宁C_(min)分布情况、目标浓度达标率及影响因素。结果38例血样C_(min)为(11.06±3.88)mg/L,其中63.2%(24/38)达标,36.8%(14/38)未达标;高剂量组较低剂量组可明显提高目标C_(min)达标率(82.4%vs 47.6%,P<0.05),肾小球滤过率(GFR)≥60mL/min/1.73m^(2)的患者达标率显著低于GFR<60mL/min/1.73m^(2)的患者(51.9%vs 90.9%,P<0.05);C_(min)未达标组的GFR明显高于C_(min)达标组[(135.03±62.22)mL/min/1.73m^(2) vs(81.8±54.62)mL/min/1.73m^(2),P<0.05]。结论重症感染患者使用≥10mg/kg的替考拉宁起始负荷剂量可较快达到有效血药谷浓度,高GFR是影响C_(min)达标的重要因素,有必要结合重症患者的药代动力学优化替考拉宁治疗剂量。

Objective To monitor serum trough concentrations(C_(min))of teicoplanin and the target concentration achieved on the 2nd day of the initial loading dose of teicoplanin in patients with severe infections,and explore the influencing factors.Methods A retrospective analysis was conducted on 38 patients with severe infections treated with teicoplanin from March 2018 to March 2019 in the Department of Intensive Care Medicine.Subjects were divided into the high dose group(≥10mg/kg)and the low dose group(<10mg/kg)according to the initial loading dose.All patients received an intravenous dose for the first three times per 12 hours.Blood samples were collected at 30min before the third dose.The C_(min) was measured by high performance liquid chromatography(HPLC).The distribution,target concentration compliance rates,and influencing factors of C_(min) of teicoplanin were analyzed retrospectively.Results The C_(min) value of 38 cases of blood samples was(11.06±3.88)mg/L,in which 63.2%(24/38)reached the target range and 36.8%(14/38)did not reach the target range.Compared with the low-dose group,the high-dose group significantly improved the target C_(min) compliance rate(82.4%vs 47.6%,P<0.05).The compliance rate of patients with glomerular filtration rate(GFR)≥60mL/min/1.73m^(2) was significantly lower than that of patients with GFR<60mL/min/1.73m^(2)(51.9%vs 90.9%,P<0.05),and the GFR of the substandard group was significantly higher than that of the standard group[(135.03±62.22)mL/min/1.73m^(2) vs(81.8±54.62)mL/min/1.73m^(2),P<0.05].Conclusions Treatment with the initial loading dose≥10mg/kg of teicoplanin can reach the effective blood concentration early in patients with severe infections,and high GFR is an important factor affecting the target concentration.It is necessary to optimize the dosage of teicoplanin combined with the pharmacokinetics of critically ill patients.