宏基因组二代测序与传统病原检测在中性粒细胞减少伴发热白血病患儿中的对比研究

doi:10.12372/jcp.2022.21e1444

Abstract

Abstract:

Objective To investigate the application value of metagenomic next-generation sequencing (mNGS) in leukemia children with febrile neutropenic (FN). Methods The clinical data of leukemia children combined with FN after chemotherapy admitted to the pediatric intensive care unit from January 1, 2018 to July 1, 2021 was retrospectively analyzed. The children were divided into group A (bloodstream infection group) and group B (pulmonary infection group) according to the infection foci, and the efficacy of mNGS and traditional pathogen detection (TPD) in the two groups was compared. Results A total of 56 children (27 boys and 29 girls) were included, with a median age of 4.0 (2.0-7.8) years. There were 39 cases in group A (28 cases of ALL and 11 cases of AML) and 17 cases in group B (10 cases of ALL and 7 cases of AML). The commonest pathogens in group A and B were Aspergillus, Candida and Acinetobacter baumannii. The consistency of positive rate of mNGS and TPD was poor (Kappa=0.039). The mNGS positive rate (80.4%) was significantly higher than TPD (58.9%), and the difference was statistically significant (P=0.023). In group A, the positive rates of mNGS for Aspergillus (35.9% vs. 12.8%), Candida (28.2% vs. 10.3%) and Acinetobacter baumannii (28.2% vs. 7.7%) were higher than those of TPD; in group B, the positive rate of mNGS for Aspergillus (41.2% vs. 5.9%) was higher than that of TPD, and the differences were statistically significant (P<0.05). The mNGS can detect rare pathogens, and the detection rate of mNGS for mixed infection was significantly higher than that of TPD, and the difference was statistically significant (P<0.05). Conclusions In leukemia children with FN who failed in initial antibiotic therapy, the commonest pathogens were Aspergillus, Candida, and Acinetobacter baumannii. As a complementary tool for TPD, mNGS has a higher positive detection rate for common pathogens and outstanding efficacy for mixed infections and rare pathogens.

Key words: metagenomic next-generation sequencing, febrile neutropenic, leukemia, child

KANG Lei, GUO Fang, BAI Xinfeng, XU Meixian. Comparative study of metagenomic next-generation sequencing and traditional pathogen detection in leukemia children with febrile neutropenia[J].Journal of Clinical Pediatrics, 2022, 40(7): 539-544.

Figures/Tables 5

References 22

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项目	A组(n=39)		统计量	P	B组(n=17)		统计量	P
项目	ALL(n=28)	AML(n=11)	统计量	P	ALL(n=10)	AML(n=7)	统计量	P
男性[n(%)]	16(57.1)	6(54.5)	χ²=0.00	1.000	3(30.0)	2(28.6)	—	0.686¹⁾
年龄 [M(P₂₅~P₇₅)]/岁	5.0 (3.0~7.0)	10.0 (2.0~12.0)	Z=1.33	0.182	3.5 (2.0~4.0)	0.8 (0.7~3.0)	Z=1.88	0.061
脓毒性休克[n(%)]	8(28.6)	1(9.1)	χ²=0.77	0.380	0(0.0)	0(0.0)	—	—
肺出血[n(%)]	3(10.7)	1(9.1)	—	1.000¹⁾	2(20.0)	0(0.0)	—	0.485¹⁾
ARDS[n(%)]	0(0.0)	0(0.0)	—	—	1(10.0)	2(28.6)	—	0.537¹⁾
存活[n(%)]	20(71.4)	10(90.9)	χ²=0.77	0.380	9(90.0)	6(85.7)	—	1.000¹⁾
SOFA评分 [M(P₂₅~P₇₅)]/分	6.0 (4.0~8.0)	7.0 (5.0~8.0)	Z=0.68	0.498	6(3~8)	5(2~8)	Z=0.45	0.656
ANC [M(P₂₅~P₇₅)]×10⁹/L	0.0 (0.0~0.1)	0.0 (0.0~0.1)	Z=1.21	0.225	0.1 (0.0~0.1)	0.1 (0.0~0.2)	Z=0.30	0.768
CRP [M(P₂₅~P₇₅)]/mg·L^-1	146.5 (57.0~231.0)	111.0 (99.0~195.0)	Z=0.19	0.851	62.5 (40.0~152.0)	102.0 (54.0~161.0)	Z=1.08	0.282
PCT [M(P₂₅~P₇₅)]/μg·L^-1	1.5 (0.2~8.3)	0.3 (0.2~1.6)	Z=1.37	0.169	0.8 (0.4~1.4)	0.2 (0.1~1.2)	Z=1.43	0.143
mNGS延迟天数 [M(P₂₅~P₇₅)]/d	10.0 (5.3~13.8)	9.0 (5.0~12.0)	Z=0.71	0.481	13.5 (4.5~24.3)	12.0 (9.0~13.0)	Z=0.49	0.624

病原	A组(n=39)		合计	B组(n=17)		合计
病原	ALL(n=28)	AML(n=11)	合计	ALL(n=10)	AML(n=7)	合计
革兰阴性菌
鲍曼不动杆菌	9(32.1)	3(27.3)	12	3(30.0)	2(28.6)	5
肺炎克雷伯菌	6(21.4)	1(9.1)	7	0(0.0)	1(14.3)	1
铜绿假单胞菌	4(14.3)	0(0.0)	4	0(0.0)	2(28.6)	2
大肠埃希氏菌	2(7.1)	1(9.1)	3	0(0.0)	0(0.0)	0
嗜麦芽窄食单胞菌	3(10.7)	0(0.0)	3	0(0.0)	0(0.0)	0
其他阴性菌	3(10.7)	1(9.1)	4	1(10.0)	1(14.3)	2
革兰阳性菌
肺炎链球菌	3(10.7)	0(0.0)	3	0(0.0)	3(42.9)	3
屎肠球菌	1(3.6)	0(0.0)	1	0(0.0)	3(42.9)	3
金黄色葡萄球菌	1(3.6)	1(9.1)	2	1(10.0)	0(0.0)	1
其他阳性菌	0(0.0)	0(0.0)	0	1(10.0)	0(0.0)	1
真菌
曲霉菌	11(39.3)	4(36.4)	15	6(60.0)	2(28.6)	8
念珠菌	9(32.1)	3(27.3)	12	2(20.0)	2(28.6)	4
肺孢子菌	0(0.0)	1(9.1)	1	0(0.0)	2(28.6)	2
毛霉菌	2(7.1)	1(9.1)	3	0(0.0)	0(0.0)	0
毛孢子菌	0(0.0)	0(0.0)	0	0(0.0)	1(14.3)	1
病毒
EBV	3(10.7)	0(0.0)	3	0(0.0)	1(14.3)	1
CMV	2(7.1)	0(0.0)	2	0(0.0)	0(0.0)	0
腺病毒	1(3.6)	0(0.0)	1	0(0.0)	0(0.0)	0

常见病原	mNGS	TPD	双阳性	双阴性	Kappa	P
A组
曲霉菌	10	1	4	24	0.286	0.012
念珠菌	8	1	3	27	0.294	0.039
鲍曼不动杆菌	9	1	2	27	0.188	0.021
B组
曲霉菌	7	0	1	9	0.131	0.016
鲍曼不动杆菌	1	3	1	12	0.209	0.625

病原体种类	mNGS	TPD	Kappa	P
0	11（19.6）	23（41.1）	0.039	0.023
1	16（28.6）	21（37.5）	0.000	0.424
≥2	29（51.8）	12（21.4）	0.055	0.002

Comparative study of metagenomic next-generation sequencing and traditional pathogen detection in leukemia children with febrile neutropenia

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