Page 101 - 2020年21期

Effects of Augmented Renal Clearance on Blood Trough Concentration of Patients Receiving High-dose
Regimen of Teicoplanin
TANG Lian ，SHI Lu ，XUE Hongzhi ，ZHUANG Zhiwei ，YUAN Yunlong ，QIAN Chunxia ，ZHU Jinwei ，XU
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Xiaowen ，ZHU Yasong ，LIU Jisong ，SHEN Yi ，LU Jian（1. Dept. of Pharmacy，the Affiliated Suzhou Hospital
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of Nanjing Medical University/Suzhou Municipal Hospital，Jiangsu Suzhou 215002，China；2. Intensive Care
Unit，the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital，Jiangsu Suzhou
215002，China；3. Medical Laboratory，the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou
Municipal Hospital，Jiangsu Suzhou 215002，China；4. College of Pharmacy，Xuzhou Medical University，
Jiangsu Xuzhou 221004，China；5. Medical Laboratory of Hangzhou Baichen，Hangzhou 310000，China）
ABSTRACT OBJECTIVE：To study the effects of augmented renal clearance（ARC）on blood trough concentration of patients
receiving high-dose regimen of teicoplanin. METHODS：Patients who received high-dose regimen of teicoplanin in the ICU were
prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul.
2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance.
The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg，q12 h×3 doses，maintenance dose of 6-10
mg/kg，qd，and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough
concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by
HPLC. Trough concentration，clinical efficacy，Gram-positive bacterial clearance rate and the occurrence of ADR were compared
between 2 groups. RESULTS：A total of 56 patients were included and divided into ARC group （18 cases） and normal renal
function group（38 cases）. ARC group had younger age（P＜0.001）and lower serum albumin level（P＝0.025）than normal renal
function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than
normal renal function group（P＝0.034；P＝0.035）. The trough concentrations in the ARC group and normal renal function group
before 8th-10th dosage were all higher than 30 min before the 4th dosage（P＝0.003；P＜0.001）. The clinical efficacy rate and the
clearance rate of Gram-positive bacteria in ARC group were 77.8％ and 76.2％，which were lower than those of the normal renal
function group，but there was no statistical difference（P＝0.195；P＝0.223）. There was no liver function damage，hemocytopenia
and allergic reaction in both groups，but in the normal renal function group，the causal relationship between acute renal damage
and teicoplanin was assessed as“very likely”in one patient. CONCLUSIONS：ARC patients are younger，most of them have
hypoproteinemia，and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of
normal renal function patients. For critical ill ARC patients，it is advisable to increase the loading dose of teicoplanin to make the
trough concentration reach the target concentration range quickly.
KEYWORDS Augmented renal clearance；Teicoplanin；High dosage；Blood trough concentration；Clinical efficacy

肾功能亢进（ARC）是危重症患者肾功能增强的一 对药物的清除速度也会有所不同，因此从理论上讲ARC
种表现，目前定义为肌酐清除率超过130 mL/（min·1.73 状态可影响替考拉宁的血药浓度。目前，尚未见有关
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m） 。ARC增加了肾脏对药物的清除，并对原型经肾 ARC 患者使用替考拉宁的治疗药物监测（TDM）研究，
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脏排泄的抗菌药物的血药浓度有显著影响，因此需考虑 针对ARC患者的替考拉宁最优给药方案还未知。鉴于
在ARC患者中使用更高的给药剂量 [3-4] 。替考拉宁是糖 此，本研究前瞻性地收集替考拉宁目标性抗感染治疗的
肽类抗菌药物，广泛用于治疗耐药革兰氏阳性菌感染， ARC患者和肾功能正常的患者，对其血药浓度监测结果
而且对耐甲氧西林金黄色葡萄球菌感染及肠球菌感染 和临床疗效进行比较分析，为ARC患者的替考拉宁个体
与万古霉素一样有效，该药的主要优势为组织穿透性 化用药调整提供参考依据。
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好、肾毒性较低 。替考拉宁的血药谷浓度与临床疗效 1 资料与方法
密切相关，其药品说明书及临床应用剂量专家共识推 1.1 纳入与排除标准
荐：对一般感染者，替考拉宁血药谷浓度应达到10 mg/L 1.1.1 纳入标准
以上；而对于严重的革兰氏阳性菌感染者，替考拉宁的 （1）经临床医师确诊为革兰氏阳性菌引起感染者，
血药谷浓度需达到15～30 mg/L [5-6] 。更新后的替考拉宁 感染性疾病包括呼吸道感染、血流感染、导管相关感染、
说明书推荐：一般感染者，采用负荷剂量6 mg/kg，q12 h× 感染性心内膜炎、中性粒细胞减少伴发热、骨关节感染、
3～5 剂；而对于脓毒血症、骨和关节感染以及感染性心 腹腔感染、皮肤软组织感染等；（2）静脉使用替考拉宁抗
内膜炎等危重症感染、严重耐药菌感染者，起始负荷剂 感染治疗者；（3）年龄≥18 岁者；（4）肌酐清除率≥50
量方案为 12 mg/kg，q12 h×3～5 剂 。肾功能状态不同 mL/（min·1.73 m）者；（5）测定了替考拉宁第 4 剂和第
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中国药房 2020年第31卷第21期 China Pharmacy 2020 Vol. 31 No. 21 ·2651 ·