60例次老年重症患者硫酸黏菌素谷浓度分布情况及结果分析

Trough concentration distribution and results analysis of colistin sulfate in 60 critical elderly patients

目的了解静脉使用硫酸黏菌素(CS)的老年重症患者达到稳态后血药谷浓度的分布情况,并分析影响谷浓度的因素。方法采用前瞻性、单中心、观察性研究。选择2021年12月至2023年2月入住山东第一医科大学附属聊城市人民医院重症医学科静脉使用CS的老年患者,纳入存在多重耐药革兰阴性杆菌感染、静脉滴注(静滴)CS超过5 d的年龄≥60周岁的患者作为研究对象,并排除无尿或需行肾脏替代治疗者。患者首剂给予1000 kU负荷剂量CS后以维持剂量500 kU、每12 h 1次静脉给药,在给药6次后,分别于第4、5、6 d监测药物谷浓度。分析血药谷浓度的分布情况、影响因素,并观察临床疗效及不良反应。结果共纳入20例患者共计60例次CS谷浓度检测结果,20例患者中男性14例,女性6例;年龄78.0(69.5,88.0)岁;急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)为19.50(18.00,27.75)分;均为呼吸系统感染,其中1例合并血流感染,1例合并尿路感染;感染菌种为耐碳青霉烯鲍曼不动杆菌(CRAB)、耐碳青霉烯铜绿假单胞菌(CRPA)、耐碳青霉烯肺炎克雷伯杆菌(CRKP)。CS谷浓度分布范围为0.20~4.10 mg/L,平均(1.31±0.87)mg/L,其中谷浓度≥最低抑菌浓度(MIC)者占73.33%(44/60)。临床有效率为55.0%(11/20);用药后出现急性肾损伤(AKI)者2例,未观察到其他不良反应。患者不同性别、体质量、中性粒细胞计数(NEUT)、降钙素原(PCT)、APACHEⅡ评分、临床疗效的谷浓度水平比较差异无统计学意义(均P>0.05);而不同年龄、白细胞计数(WBC)、血肌酐(SCr)、肌酐清除率(CCr)的谷浓度水平比较差异均有统计学意义(均P<0.05)。年龄>75岁者CS谷浓度明显高于60~75岁者(mg/L:1.79±0.76比0.76±0.64,P=0.000),WBC(4~10)×10^(9)/L者谷浓度明显高于>10×10^(9)/L者(mg/L:1.55±0.76比1.01±0.92,P=0.015),SCr>110μmol/L者谷浓度明显高于≤110μmol/L者(mg/L:2.13±1.13比1.10±0.66,P=0.010),CCr<80 mL/min者谷浓度明显高于≥80 mL/min者(mg/L:1.73±0.80比0.68±0.54,P=0.000),其中不同年龄、CCr(计算CCr时包含年龄)患者之间的谷浓度差异显著。结论老年重症患者静滴CS稳态时谷浓度分布差异较大,应用指南推荐剂量中的最低维持剂量并非老年患者的安全剂量。CCr和年龄因素对CS谷浓度的影响最为显著,建议临床上针对老年患者根据CCr调整用药剂量。

Objective To understand the distribution of steady-state drug trough concentration in elderly patients with intravenous Colistin sulfate(CS)and analyze factors affecting trough concentration.Methods A prospective,single-center,observational study was conducted to select elderly patients admitted to the department of critical care medicine of Liaocheng People's Hospital Affiliated to Shandong First Medical University with intravenous CS from December 2021 to February 2023.Patients aged≥60 years with multidrug-resistant Gram-negative(G-)bacillus infection who had been given intravenous CS for more than 5 days were enrolled,and excluded from those who were anuric or required renal replacement therapy.After the first dose of 1000 kU load dose of CS,a maintenance dose of 500 kU/12 hours was administered intravenously.After 6 doses,the drug trough concentration was monitored on day 4,5,and 6,respectively.The distribution and influencing factors of serum drug trough concentration were analyzed,and the clinical efficacy and adverse reactions were observed.Results A total of 60 CS trough concentration test results were included in 20 patients including 14 males and 6 females,aged 78.0(69.5,88.0)years old.Acute physiological and chronic health evaluationⅡ(APACHEⅡ)were 19.50(18.00,27.75)points.All of them were respiratory system infections,1 case was combined with bloodstream infection and 1 case was combined with urinary tract infection.The infected strains were carbapenem-resistant Acinetobacter baumannii(CRAB),carbapenem-resistant Pseudomonas aeruginosa(CRPA),and carbapenem-resistant Klebsiella pneumoniae(CRKP).The trough concentration of CS ranged from 0.20-4.10 mg/L,with an average of(1.31±0.87)mg/L.Among them,73.33%(44/60)have trough concentration≥minimum inhibitory concentration(MIC).The clinical effective rate was 55.0%(11/20).Acute kidney injury(AKI)occurred in 2 cases,and no other adverse reactions were observed.There was no statistical significant difference the level of valley concentration between different Gender,body weight,neutrophil count(NEUT),procalcitonin(PCT),APACHEⅡscore and clinical efficacy;while there was statistical significant difference the level of trough concentration between different age,white blood cell count(WBC),serum creatinine rate(SCr)and creatinine clearance rate(CCr).The CS trough concentration in patients aged>75 years was significantly higher than that in those aged 60-75 years(mg/L:1.79±0.76 vs.0.76±0.64,P=0.000),and the CS trough concentration in patients with WBC(4-10)×10^(9)/L was higher than that in patients with WBC>10×10^(9)/L(mg/L:1.55±0.76 vs.1.01±0.92,P=0.015),the CS trough concentration in patients with SCr>110μmo/L was higher than those with SCr≤110μmol/L(mg/L:2.13±1.13 vs.1.10±0.66,P=0.010),the CS trough concentration in patients with CCr<80 mL/min was significantly higher than those with CCr≥80 mL/min(mg/L:1.73±0.80 vs.0.68±0.54,P=0.000),among which there were significant intergroup differences in the trough concentration among patients with different ages and CCr(CCr included age factor in the calculation).Conclusions The distribution of steady-state serum trough concentration varies greatly in elderly patients with intravenous colistin sulfate.The minimum maintenance dosage recommended in the application guidelines is not the safe dose for elderly patients.CCr and age factors have the most significant influence on CS trough concentration,and it is recommended to adjust the dosage according to CCr in clinical practice for elderly patients.