45例有创机械通气重症结核病患者静脉使用抗结核药物血药浓度分析

doi:10.19982/j.issn.1000-6621.20250030

摘要/Abstract

摘要： 选取2022年4月至2024年10月在武汉市肺科医院重症医学科行气管插管有创机械通气治疗,因胃肠功能障碍需静脉抗结核治疗并监测抗结核药物血药浓度的45例重症结核病患者作为研究对象,收集患者年龄、性别、急性胃肠功能障碍评分(AGI)、急性生理与慢性健康评分Ⅱ(APACHE Ⅱ),是否合并糖尿病、感染性休克,抗结核治疗期间是否出现肝功能异常、肾功能异常,是否行连续性肾脏替代治疗(CRRT)等资料,以及常用静脉抗结核药异烟肼(INH)、利福平(RFP)、莫西沙星(Mfx)、左氧氟沙星(Lfx)、利奈唑胺(Lzd)、阿米卡星(Am)的血药浓度。结果显示,45例患者中INH、RFP、Mfx、Lfx和Lzd的血药浓度在专家共识推荐的目标范围的构成比分别为30.8%(12/39)、54.1%(20/37)、53.3%(8/15)、3/9、5/9,使用Am的3例患者,其血药浓度均未在目标范围。INH、RFP、Mfx、Lfx、Lzd和Am血药浓度与年龄、性别、是否合并糖尿病、是否合并感染性休克不相关(P值均>0.05)。在联合CRRT患者中,RFP血药浓度<8mg/L占16.2%(6/37),8~24mg/L占2.7% (1/37),>24mg/L占2.7% (1/37),而未联合CRRT患者中,RFP血药浓度<8mg/L占18.9%(7/37),8~24mg/L占51.4%(19/37),>24mg/L占8.1%(3/37),RFP血药浓度与联合CRRT治疗相关(χ²=7.817,P=0.012)。APACHE Ⅱ评分高低与INH、RFP、Mfx、Lfx、Lzd和Am血药浓度无相关性(P>0.05),血药浓度水平与是否出现肝功能异常、肾功能异常亦无相关性(P>0.05)。可见,重症结核病患者病情复杂,在使用常用抗结核药物后,血药浓度未能达到专家共识推荐的目标范围的情况较为普遍,联合CRRT治疗对RFP血药浓度有一定的影响,临床上需严密监测。

关键词: 结核, 抗结核药, 药物监测, 重症监护, 通气机,机械

Abstract:

This study enrolled 45 critically ill tuberculosis (TB) patients requiring endotracheal intubation and invasive mechanical ventilation in the ICU of Wuhan Pulmonary Hospital from April 2022 to October 2024. All patients had gastrointestinal dysfunction necessitating intravenous anti-TB therapy and therapeutic drug monitoring (TDM). Data collected included age, sex, Acute Gastrointestinal Injury (AGI) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, comorbidities (diabetes, septic shock), occurrence of hepatic/renal dysfunction during treatment, use of continuous renal replacement therapy (CRRT), and serum concentrations of intravenous anti-TB drugs: isoniazid (INH), rifampicin (RFP), moxifloxacin (Mfx)/levofloxacin (Lfx), linezolid (Lzd), and amikacin (Am). Results showed that among patients receiving ≥2 anti-TB drugs, the proportions achieving target concentrations were: INH 30.7% (12/39), RFP 54.1% (20/37), Mfx 53.3% (8/15), Lfx (3/9), Lzd (5/9), and Am 0.00% (0/3). Drug concentrations showed no correlation with age, sex, diabetes, or shock (P>0.05). In CRRT-treated patients, RFP concentrations were <8 mg/L in 16.2% (6/37), 8-24 mg/L in 2.7% (1/37), and >24 mg/L in 2.7% (1/37). In non-CRRT patients, RFP concentrations were <8 mg/L in 18.9% (7/37), 8-24 mg/L in 51.4% (19/37), and >24 mg/L in 8.1% (3/37), indicating a significant association between RFP concentration and CRRT (χ²=7.817, P=0.012). APACHE Ⅱ scores showed no correlation with drug concentrations (P>0.05), nor did hepatic/renal dysfunction (P>0.05). In conclusion,patients with severe tuberculosis present complex clinical conditions.Therapeutic concentrations of anti-TB drugs recommended target ranges are commonly observed, and concomitant CRRT may affect RFP pharmacokinetics, necessitating rigorous therapeutic drug monitoring in clinical practice.

Key words: Tuberculosis, Antitubercular agents, Drug monitoring, Intensive care, Ventilators, mechanical

中图分类号:

R825.2

黄伟强, 袁楚楚, 张欢, 王丽丽, 钟小锋, 陈星星, 胡明. 45例有创机械通气重症结核病患者静脉使用抗结核药物血药浓度分析[J]. 中国防痨杂志, 2025, 47(6): 798-807. doi: 10.19982/j.issn.1000-6621.20250030

Huang Weiqiang, Yuan Chuchu, Zhang Huan, Wang Lili, Zhong Xiaofeng, Chen Xingxing, Hu Ming. Analysis of blood concentrations of intravenous antituberculosis drugs in 45 mechanically ventilated patients with severe tuberculosis[J]. Chinese Journal of Antituberculosis, 2025, 47(6): 798-807. doi: 10.19982/j.issn.1000-6621.20250030

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参考文献 18

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药物血药浓度范围 (mg/L)	患者 [例(构成比,%)]	平均血药浓度 (mg/L, $\bar{x}±s$)
INH
<3.0	9(23.1)	1.57±0.88
3.0~6.0	12(30.8)	5.18±0.60
>6.0	18(46.1)	10.12±3.25
合计	39(100.0)	6.81±4.46
RFP
<8.0	13(35.1)	5.35±2.14
8.0~24.0	20(54.1)	14.10±4.33
>24.0	4(10.8)	27.00±2.23
合计	37(100.0)	12.42±7.42
Mfx
<2.5	1(6.7)	2.10
2.5~5.0	8(53.3)	3.98±0.66
>5.0	6(40.0)	6.37±0.91
合计	15(100.0)	4.81±1.57
Lfx
<8.0	2(2/9)	7.10±1.13
8.0~13.0	3(3/9)	10.70±0.82
>13.0	4(4/9)	15.80±1.59
合计	9(9/9)	12.17±3.89
Lzd
<12.0	3(3/9)	8.73±2.50
12.0~26.0	5(5/9)	21.76±3.80
>26.0	1(1/9)	29.80
合计	9(9/9)	18.31±8.19
Am
<35.0	1(1/3)	25.9
35.0~45.0	0(0/3)	-
>45.0	2(2/3)	63.20±16.69
合计	3(3/3)	50.77±24.56

药物血药浓度范围 (mg/L)	年龄[例,构成比(%)]		χ²值	P值
药物血药浓度范围 (mg/L)	<60岁(10例)	≥60岁(35例)	χ²值	P值
INH			1.548	0.497
<3.0	4(10.3)	5(12.8)
3.0~6.0	4(10.3)	8(20.5)
>6.0	4(10.3)	14(35.9)
合计	12(30.8)	27(69.2)
RFP			2.614	0.220
<8.0	6(16.2)	7(18.9)
8.0~24.0	4(10.8)	16(43.2)
>24.0	1(2.7)	3(8.1)
合计	11(29.7)	26(70.3)
Mfx			3.369	0.276
<2.5	0(0.0)	1(6.7)
2.5~5.0	0(0.0)	8(65.3)
>5.0	2(100.0)	4(26.7)
合计	2(13.3)	13(86.7)
Lfx			1.457	0.714
<8.0	1(1/9)	1(1/9)
8.0~13.0	2(2/9)	1(1/9)
>13.0	1(1/9)	3(3/9)
合计	4(4/9)	5(5/9)
Lzd			1.075	1.000
<12.0	1(1/9)	2(2/9)
12.0~26.0	1(1/9)	4(4/9)
>26.0	0(0/9)	1(1/9)
合计	2(2/9)	7(7/9)
Am			-^a	0.667
<35.0	1(1/3)	0(0/3)
35.0~45.0	0(0/3)	0(0/3)
>45.0	1(1/3)	1(1/3)
合计	2(2/3)	1(1/3)

药物血药浓度范围 (mg/L)	性别[例,构成比(%)]		χ²值	P值
药物血药浓度范围 (mg/L)	男性(33例)	女性(12例)	χ²值	P值
INH			3.521	0.213
<3.0	6(15.4)	3(7.7)
3.0~6.0	11(28.2)	1(2.6)
>6.0	11(28.2)	7(18.0)
合计	28(71.8)	11(28.2)
RFP			3.807	0.128
<8.0	12(32.4)	1(2.7)
8.0~24.0	14(37.8)	6(16.2)
>24.0	2(5.4)	2(5.4)
合计	28(75.7)	9(24.3)
Mfx			0.782	1.000
<2.5	1(6.7)	0(0.0)
2.5~5.0	6(40.0)	2(13.3)
>5.0	4(26.7)	2(13.3)
合计	11(73.3)	4(26.7)
Lfx			-	-
<8.0	2(2/9)	-
8.0~13.0	3(3/9)	-
>13.0	4(4/9)	-
合计	9(9/9)	0(0.0)
Lzd			3.078	0.286
<12.0	3(3/9)	0(0/9)
12.0~26.0	3(3/9)	2(2/9)
>26.0	0(0/9)	1(1/9)
合计	6(6/9)	3(3/9)
Am			-	-
<35.0	1(1/3)	-
35.0~45.0	0(0/3)	-
>45.0	2(2/3)	-
合计	3(3/3)	-

药物血药浓度范围 (mg/L)	糖尿病[例,构成比(%)]			χ²值	P值
药物血药浓度范围 (mg/L)	是(13例)		否(32例)	χ²值	P值
INH				0.631	0.432
<3.0	3(7.7)		6(15.4)
3.0~6.0	2(5.1)		10(25.6)
>6.0	6(15.4)		12(30.8)
合计	11(28.2)		28(71.8)
RFP				2.378	0.349
<8.0	5(13.5)		8(21.6)
8.0~24.0	4(10.8)		16(43.2)
>24.0	2(5.4)		2(5.4)
合计	11(29.7)		26(70.3)
Mfx				2.103	0.534
<2.5		1(6.7)	0(0.0)
2.5~5.0		2(13.3)	6(40.0)
>5.0		2(13.3)	4(20.7)
合计		5(33.3)	10(66.7)
Lfx				1.862	0.667
<8.0		1(1/9)	1(1/9)
8.0~13.0		0(0/9)	3(3/9)
>13.0		1(1/9)	3(3/9)
合计		2(2/9)	7(7/9)
Lzd				2.641	0.444
<12.0		1(1/9)	2(2/9)
12.0~26.0		0(0/9)	5(5/9)
>26.0		0(0/9)	1(1/9)
合计		1(1/9)	8(8/9)
Am				-^a	0.333
<35.0		1(1/3)	0(0/3)
35.0~45.0		0(0.00)	0(0/3)
>45.0		0(0/3)	2(2/3)
合计		1(1/3)	2(2/3)

药物血药浓度范围 (mg/L)	感染性休克[例,构成比(%)]				χ²值	P值
药物血药浓度范围 (mg/L)	是(16例)		否(29例)		χ²值	P值
INH					0.131	1.000
<3.0	3(7.7)		6(15.4)
3.0~6.0	4(10.3)		8(20.5)
>6.0	6(15.4)		12(30.8)
合计	13(33.3)		26(66.7)
RFP					2.378	0.349
<8.0	5(13.5)		8(21.6)
8.0~24.0	4(10.8)		16(43.2)
>24.0	2(5.4)		2(5.4)
合计	11(29.7)		26(70.3)
Mfx					2.396	0.399
<2.5	1(6.7)		0(0.0)
2.5~5.0	2(13.3)		6(40.0)
>5.0	3(20.0)		3(20.0)
合计	6(40.0)		9(60.0)
Lfx					2.982	0.222
<8.0	1(1/9)		1(1/9)
8.0~13.0	0(0.00)		3(3/9)
>13.0	0(0.00)		4(4/9)
合计	1(1/9)		8(8/9)
Lzd				2.267		0.643
<12.0		1(1/9)	2(2/9)
12.0~26.0		1(1/9)	4(4/9)
>26.0		1(1/9)	0(0.00)
合计		3(3/9)	6(6/9)
Am				-^a		1.000
<35.0		1(1/3)	0(0/3)
35.0~45.0		0(0/3)	0(0/3)
>45.0		1(1/3)	1(1/3)
合计		2(2/3)	1(1/3)