Metagenomics next-generation sequencing for assisting the diagnosis of mucormycosis: a case report and literature review

doi:10.3877/cma.j.issn.1674-1358.2022.01.008

Abstract

Abstract:

Objective

To explore the clinical application value of metagenomics next-generation sequencing (mNGS) in assisting the diagnosis of invasive fungal diseases, and to provide pathogenic evidence for the clinical diagnosis and treatment of mucormycosis.

Methods

The alveolar lavage fluid of a patient with unexplained lung infection was detected by mNGS to determine the pathogen, and the treatment plan was adjusted according to the mNGS test report.

Results

The patient had intermittent chest pain and cough for longer than 5 months. The chest CT showed multiple shadows and cavities in both lungs. There was no abnormality in routine laboratory and pathogenic examinations, and no significant improvement was found after various anti-infection treatments. The mNGS of alveolar lavage fluid submitted for examination revealed that the pathogen was Lichtheimia ramose. After switching to amphotericin B for anti-infection treatment, the patient’s infected lesions shrank and the symptoms relieved significantly.

Conclusions

mNGS is an important auxiliary diagnostic method to identify rare pathogens, which is of great significance to assist the diagnosis of lung invasive mycosis.

Key words: Metagenomic next-generation sequencing, Invasive fungal pneumonia, Mucormycosis, Lichtheimia ramose

Ying Song, Jiangqin Song, Fuying Hu, Huashun Li, Youjun Tian, Yan Ding, Junyang Zhou. Metagenomics next-generation sequencing for assisting the diagnosis of mucormycosis: a case report and literature review[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(01): 54-59.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-1358.2022.01.008

https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/Y2022/V16/I01/54

Figures/Tables 5

References 25

[1]	Kutlu M, Ergin C, Bir F, et al. Pulmonary mucormycosis due to Lichtheimia ramosa in a patient with HIV infection[J]. Mycopathologia,2014,178(1-2):111-115.
[2]	Trastoy R, Manso T, Garc a X, et al. Pulmonary co-infection due to Nocardia cyriacigeorgica and Aspergillus fumigatus[J]. Rev EspQuimioter,2017,30(2):123-126.
[3]	Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease[J]. Clin Microbiol Rev,2000,13(2):236-301.
[4]	Sintchenko V, Holmes EC. The role of pathogen genomics in assessing disease transmission[J]. BMJ,2015,350:h1314.
[5]	林爱清，张璐，成宝涛, 等. 二代测序技术应用于脑脊液检测在结核性脑膜炎中的早期诊断价值[J/CD]. 中华实验和临床感染病杂志(电子版),2020,14(4):291-295.
[6]	杨理，顾佳，龙筱露, 等. 利用高通量宏基因组测序技术检测血液病患者感染性病原体的横断面研究[J/CD]. 中华实验和临床感染病杂志(电子版),2020,14(2):99-103.
[7]	Alastruey-Izquierdo A, Hoffmann K, de Hoog GS, et al. Species recognition and clinical relevance of the zygomycetous genus Lichtheimia (syn. Absidia pro parte, Mycocladus)[J]. J Clin Microbiol,2010,48(6):2154-2170.
[8]	Kurosawa M, Yonezumi M, Hashino S, et al. Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies[J]. Int J Hematol,2012,96(6):748- 757.
[9]	Shimodaira K, Okubo Y, Nakayama H, et al. Trends in the prevalence of invasive fungal infections from an analysis of annual records of autopsy cases of Toho University[J]. Mycoses,2012,55(5):435-443.
[10]	Guinea J, Escribano P, Vena A, et al. Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: Epidemiology and microbiological characterization of the isolates[J]. PLoS One,2017,12(6):e179136.
[11]	Zhang Q, Liu H, Qiu S, et al. A rare case of pulmonary coinfection by Lichtheimia ramosa and Aspergillus fumigatus in a patient with delayed graft function after renal transplantation[J]. Transplant Proc,2019,51(2):551-555.
[12]	Gerlach MM, Lippmann N, Kobelt L, et al. Possible pulmonary Rhizopus oryzae infection in a previously healthy child after anear-drowning incident[J]. Infection,2016,44(3):361-364.
[13]	Zhang K, Yu C, Li Y, et al. Next-generation sequencing technology for detecting pulmonary fungal infection in bronchoalveolar lavage fluid of a patient with dermatomyositis: a case report and literature review[J]. BMC Infect Dis,2020,20(1):608.
[14]	Szelnyi H, Foss HD, Kreuser ED, et al. Fatal Mucor pneumonia after treatment with 2-chlorodeoxyadenosine fornon-Hodgkin’s-lymphoma[J]. Ann Hematol,1996,73(3):145-147.
[15]	Hamdi T, Karthikeyan V, Alangaden GJ. Mucormycosis in a renal transplant recipient: case report and comprehensive review of literature[J]. Int J Nephrol,2014,2014:950643.
[16]	Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis[J]. Lancet Infect Dis,2005,5(10):609-622.
[17]	郑微，赵鹏，张永宏, 等. 宏基因组测序技术分析原发性肝癌患者肠道菌群特征[J/CD]. 中华实验和临床感染病杂志(电子版),2021,15(3):149-157.
[18]	刘鑫喆，滑明溪，王慧珠, 等. 基于全基因组序列的耐碳青霉烯鲍曼不动杆菌的耐药与毒力研究[J/CD]. 中华实验和临床感染病杂志(电子版),2020,14(5):367-373.
[19]	Zhang X, Liang Z, Wang S, et al. Application of next-generation sequencing technology to precision medicine incancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology[J]. Cancer Biol Med,2019,16(1):189-204.
[20]	Long Y, Zhang Y, Gong Y, et al. Diagnosis of sepsis with cell-free DNA by next-generation sequencing technology in ICU patients[J]. Arch Med Res,2016,47(5):365-371.
[21]	周彩存，王洁，程颖, 等. 二代测序技术在NSCLC中的临床应用中国专家共识(2020版)[J]. 中国肺癌杂志,2020,23(9):741-761.
[22]	刘孝荣，马东礼，姜含芳, 等. 高通量测序方法在重症肺炎病原体检测的应用[J]. 中华检验医学杂志,2017,40(8):609-613.
[23]	Yohe S, Thyagarajan B. Review of clinical next-generation sequencing[J]. Arch Pathol Lab Med,2017,141(11):1544-1557.
[24]	Boers SA, Jansen R, Hays JP. Understanding and overcoming the pitfalls and biases of next-generation sequencing (NGS) methods for use in the routine clinical microbiological diagnostic laboratory[J]. Eur J Clin Microbiol Infect Dis,2019,38(6):1059-1070.
[25]	Kaneko Y, Oinuma KI, Terachi T, et al. Successful treatment of intestinal mycosis caused by a simultaneous infection with Lichtheimia ramosa and Aspergillus calidoustus[J]. Intern Med,2018,57(16):2421-2424.

名称		序列数	相对丰度（%）
属（Genus）
	诺卡菌属	1	0.20
	横梗霉属	264	53.77
	小克银汉霉属	4	0.82
	葡萄球菌属	25	5.09
	卟啉单胞菌属	31	6.31
种（Species）
	奶牛乳房炎性诺卡菌	1	0.20
	总状横梗霉菌	260	52.95
	灰色小克银汉霉菌	4	0.82
	表皮葡萄球菌	24	4.89
	牙龈卟啉单胞菌	30	6.11

名称		序列数	相对丰度（%）
属（Genus）
	诺卡菌属	1	0.20
	横梗霉属	264	53.77
	小克银汉霉属	4	0.82
	葡萄球菌属	25	5.09
	卟啉单胞菌属	31	6.31
种（Species）
	奶牛乳房炎性诺卡菌	1	0.20
	总状横梗霉菌	260	52.95
	灰色小克银汉霉菌	4	0.82
	表皮葡萄球菌	24	4.89
	牙龈卟啉单胞菌	30	6.11

指标	正常参考值	3月26日	3月27日	4月3日	4月24日	8月18日	8月29日	9月23日
白细胞（× 10⁹/L）	3.5~9.5	8.02	6.76	5.57	5.16	10.54	7.54	6.02
中性粒细胞（× 10⁹/L）	1.8~6.3	6.29	5.36	3.98	3.61	9.42	5.87	4.45
中性粒细胞比率（%）	40~75	78.50	79.20	71.40	69.90	89.30	77.90	74.00
淋巴细胞（× 10⁹/L）	1.1~3.2	1.18	0.83	0.84	0.68	0.67	1.13	0.83
淋巴细胞百分比（%）	20~50	14.70	12.30	16.90	13.20	6.40	15.00	13.80
CRP（mg/L）	≤ 6	9.99	11.32	5.15	8.96	35.08	5.77	35.94
ESR（mm/h）	0~20	—	11.00	68.2	—	56.00	30.00	45.00

指标	正常参考值	3月26日	3月27日	4月3日	4月24日	8月18日	8月29日	9月23日
白细胞（× 10⁹/L）	3.5~9.5	8.02	6.76	5.57	5.16	10.54	7.54	6.02
中性粒细胞（× 10⁹/L）	1.8~6.3	6.29	5.36	3.98	3.61	9.42	5.87	4.45
中性粒细胞比率（%）	40~75	78.50	79.20	71.40	69.90	89.30	77.90	74.00
淋巴细胞（× 10⁹/L）	1.1~3.2	1.18	0.83	0.84	0.68	0.67	1.13	0.83
淋巴细胞百分比（%）	20~50	14.70	12.30	16.90	13.20	6.40	15.00	13.80
CRP（mg/L）	≤ 6	9.99	11.32	5.15	8.96	35.08	5.77	35.94
ESR（mm/h）	0~20	—	11.00	68.2	—	56.00	30.00	45.00

指标	正常参考值	9月21日	9月23日	9月25日	9月27日	9月29日	10月1日	10月5日
血钾	3.5~5.3	4.61	3.22	3.02	2.72	2.91	3.34	3.56
尿素（mmol/L）	3.1~8	4.55	8.63	7.73	7.25	6.35	8.11	8.75
肌酐（mmol/L）	57~97	90.1	140.1	132.7	136.4	127.1	163.4	138.3

Please choose a citation manager

Content to export