Analysis of incidence and risk factors for linezolid-related hematological side effects: a multicenter cohort study

doi:10.19982/j.issn.1000-6621.20240539

Abstract

Abstract:

Objective: To investigate the incidence of hematological side effect (HSE) in patients with drug-resistant tuberculosis treated with a linezolid-containing regimen and to explore the risk factors. Methods: This study included drug-resistant tuberculosis patients who visited three medical institutions centers in three different regions of China from May 2023 to May 2024. Demographic characteristics (age, sex, weight, etc.), hematological test results (white blood cell count, hemoglobin, platelet count, etc.), the time and severity of adverse reactions, anti-tuberculosis treatment regimens, treatment outcomes and other information of all patients were collected. Univariate analysis and multivariate logistic regression analysis were used to screen high-risk factors. Results: The incidence of linezolid-related HSE was 45.5% (122/268), with a higher rate in males than in females (59.8%, 73/122 vs. 40.2%, 49/122) and the greatest proportion in the 40-59 age group accounted for 35.3% (43/122). Time of onset of linezolid-related HSE was between 1 to 29 weeks, with a median of 13 (12,24) weeks. Sixteen patients (13.1%, 16/122) developed leukopenia, with 7 cases at grade 1, 8 cases at grade 2, and 1 case at grade 3. One hundred and eleven patients (91.0%, 111/122) developed anemia, with 45 cases at grade 1, 54 cases at grade 2, and 12 cases at grade 3. Six patients (4.9%, 6/122) experienced thrombocytopenia, with 4 cases at grade1, 1 case at grade 2, and 1 case at grade 3. Eleven patients (9.0%, 11/12) experienced both anemia and leukopenia; 6 patients (4.9%, 6/122) had both anemia and thrombocytopenia; 1 patient (0.8%, 1/122) had leukopenia, anemia, and thrombocytopenia simultaneously. No bleeding disorders occurred in any of patients. Logistic regression analysis showed that the risk of linezolid-related HSE was 20.136 (95%CI: 4.843-83.714) times higher in patients in pre-treatment hypoalbuminemia (<35 g/L) than in those with albumin levels ≥35 g/L. Conclusion: The incidence of linezolid-related HSE was high, which was more common in 40-59 age group, more in males than in females, and anemia was the most common. HSE was mostly mild to moderate, and hematological parameters could return to normal after treatment. Patients with low serum albumin levels before treatment were prone to linezolid-related HSE.

Key words: Linezolid, Tuberculosis, Drug resistance, Toxic actions, Factor analysis, statistical, Multicenter study

CLC Number:

Li Xuelian, Zhu Qingdong, Ma Yijing, Tusongjiang Maituoheti, Miriguli Maituoheti, Wang Qingfeng, Ma Liping, Chu Naihui, Nie Wenjuan, Lin Yanrong, Li Wei, Wang Jing. Analysis of incidence and risk factors for linezolid-related hematological side effects: a multicenter cohort study[J]. Chinese Journal of Antituberculosis, 2025, 47(6): 719-726. doi: 10.19982/j.issn.1000-6621.20240539

Figures/Tables 6

References 25

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分类	例数	发生率 (%)	发生时间 [周,M(Q₁,Q₃)]	分类	例数	发生率 (%)	发生时间 [周,M(Q₁,Q₃)]
贫血	111	91.0	13(12,24)	血小板减少	6	4.9	12(2,24)
1级	45	40.5^a		1级	4	4/6^a
2级	54	48.6^a		2级	1	1/6^a
3级	12	10.9^a		3级	1	1/6^a
白细胞减少	16	13.1	24(13,28)	贫血+白细胞减少	11	9.0
1级	7	43.8^a		贫血+血小板减少	6	4.9
2级	8	50.0^a		贫血+白细胞减少+血小板减少	1	0.8
3级	1	6.2^a

因素		HSE组(122例)		NHSE组(146例)		χ²值		P值
年龄组(岁)						0.081		0.775
14~39		42(34.4)		60(41.1)
40~59		43(35.3)		50(34.2)
60~79		36(29.5)		35(24.0)
80~83		1(0.8)		1(0.7)
性别						2.177		0.140
男性		73(59.8)		100(68.5)
女性		49(40.2)		46(31.5)
体质量指数						8.807		0.003
≥18.5		76(62.3)		115(78.8)
<18.5		46(37.7)		31(21.2)
耐药情况						0.024		0.877
耐多药		49(40.2)		60(41.1)
利福平耐药		73(59.8)		86(58.9)
治疗前血液检测结果
白细胞(×10⁹/L)						2.411		0.120
≥3.5		120(98.4)		146(100.0)
<3.5		2(1.6)		0(0.0)
血小板(×10⁹/L)						1.201		0.273
≥100		121(99.2)		146(100.0)
<100		1(0.8)		0(0.0)
血红蛋白(g/L)						4.793		0.029
≥120		99(81.1)		132(90.4)
<120		23(18.9)		14(9.6)
血清白蛋白(g/L)						22.548		0.000
≥35		78(63.9)		129(88.4)
<35		44(36.1)		17(11.6)
血肌酐(μmol/L)						4.682		0.030
≥110		6(4.9)		1(0.7)
<110		116(95.1)		145(99.3)
民族						4.514		0.211
汉族		80(65.6)		87(59.6)
壮族		18(14.8)		15(10.3)
维吾尔族		21(17.2)		40(27.4)
其他民族		3(2.4)		4(2.7)
合并用药情况
使用贝达喹啉						0.982		0.322
是		47(38.5)		65(44.5)
否		75(61.5)		81(55.5)
使用氟喹诺酮类药物						0.000		0.985
是		101(82.8)		121(82.9)
否		21(17.2)		25(17.1)
使用氯法齐明						0.329		0.566
是		71(58.2)		90(61.6)
否		51(41.8)		56(38.4)
使用环丝氨酸						0.088		0.766
是		102(83.6)		124(84.9)
否		20(16.4)		22(15.1)
使用吡嗪酰胺						3.595		0.058
是		51(41.8)		78(53.4)
否		71(58.2)		68(46.6)
使用乙胺丁醇					0.081		0.775
是	34(27.9)		43(29.5)
否	88(72.1)		103(70.5)
使用阿米卡星					0.883		0.347
是	19(15.6)		17(11.6)
否	103(84.4)		129(88.4)
使用丙硫异烟胺					0.004		0.951
是	33(27.0)		39(26.7)
否	89(73.0)		107(73.3)

因素	赋值
体质量指数	≥18.5=1,<18.5=0
血清白蛋白	≥35g/L=1,<35g/L=0
血肌酐	≥110μmol/L=1,<110μmol/L=0
血红蛋白	≥120g/L=1,<120g/L=0

变量	β值	$s_{\bar{x}} $值	Wald χ²值	P值	OR值	95%CI值
体质量指数(≥18.5)	0.045	0.892	0.003	0.960	1.046	0.182~6.010
血清白蛋白(≥35g/L)	3.003	0.727	17.057	0.000	20.136	4.843~83.714
血肌酐(≥110μmol/L)	12.309	3090.570	0.000	0.997	221636.451	0.000~63.290
血红蛋白(≥120g/L)	33.520	4355.937	0.000	0.994	3.610×10¹⁴	0.000~96.000
常量	―32.804	4355.937	0.000	0.994	0.000	―