Analysis of blood concentrations of intravenous antituberculosis drugs in 45 mechanically ventilated patients with severe tuberculosis

doi:10.19982/j.issn.1000-6621.20250030

Abstract

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

CLC Number:

R825.2

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

Figures/Tables 10

References 18

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特征	患者例数	构成比(%)
性别
男性	33	73.3
女性	12	26.7
合并糖尿病
是	13	28.9
否	32	71.1
合并感染性休克
是	16	35.6
否	29	64.4
AGI分级
Ⅰ级	0	0.0
Ⅱ级	29	64.4
Ⅲ级	13	28.9
Ⅳ级	3	6.7
肝功能异常
是	16	35.6
否	29	64.4
肾功能异常
是	20	44.4
否	25	66.6
联合CRRT治疗
是	11	24.4
否	34	75.6
静脉使用抗结核药
INH	39	86.7
RFP	37	85.2
Mfx	15	33.3
Lfx	9	20.0
Lzd	9	20.0
Am	3	6.8

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)