儿童肺炎支原体肺炎多重耐药基因位点突变分析及临床意义

doi:10.7499/j.issn.1008-8830.2407129

摘要
图/表
参考文献(23)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (580 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的通过靶向高通量测序检测儿童肺炎支原体肺炎多重耐药基因位点突变，并探讨其临床意义。方法回顾性分析2023年1—12月于湖北省妇幼保健院收治的2 899例呼吸道多重病原体靶向高通量测序肺炎支原体肺炎患儿的临床资料。根据是否发生肺炎支原体大环内酯类药物耐药基因23SrRNA突变，分为突变组（n=885）和未突变组（n=2 014）。采用多因素logistic回归分析探讨儿童肺炎支原体肺炎多重耐药基因位点突变的危险因素。结果 2 899例患儿中，耐药基因23SrRNA突变885例（30.53%），其中A2063G基因位点突变884例，A2064G基因位点突变1例；发生耐药基因23SrRNA突变患儿中，使用多西环素、氧氟沙星治疗疗效优于阿奇霉素、克拉霉素，且多西环素治疗疗效优于氧氟沙星（P<0.05）。肺炎支原体肺炎患儿中，耐药基因突变率随年龄增加而上升（P<0.001）。多因素logistic回归分析显示，年龄增大、肺外感染、肺实变、发热时间延长、住院时间延长及CRP水平增高是发生耐药基因23SrRNA位点突变的危险因素（P<0.05）。结论年龄、肺外感染、肺实变、发热时间、住院时间、CRP水平与耐药基因23SrRNA位点突变密切相关。可通过检测肺炎支原体肺炎患儿体内多重耐药基因位点突变情况为患儿进行早期疾病诊断及预测治疗疗效，促进临床合理治疗。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	张未
	汪洋
	蔡丽君

关键词 ：肺炎支原体肺炎, 靶向高通量测序, 多重耐药基因位点, 儿童

Abstract：Objective To detect multidrug resistance gene locus mutations in children with Mycoplasma pneumoniae pneumonia through targeted high-throughput sequencing and to explore its clinical significance. Methods A retrospective analysis was conducted on the clinical data of 2 899 children with Mycoplasma pneumoniae pneumonia, who underwent respiratory pathogen-targeted high-throughput sequencing, treated at Hubei Maternal and Child Health Care Hospital between January and December 2023. The patients were divided into a mutation group (n=885) and a non-mutation group (n=2 014) based on whether there was a mutation in the 23SrRNA macrolide-resistant gene of Mycoplasma pneumoniae. Multivariate logistic regression analysis was used to investigate the risk factors for multidrug resistance gene locus mutations in children with Mycoplasma pneumoniae pneumonia. Results Among the 2 899 children, 885 cases (30.53%) had mutations in the 23SrRNA resistance gene, including 884 cases with the A2063G mutation and 1 case with the A2064G mutation. In children with 23SrRNA resistance gene mutations, treatment with doxycycline or ofloxacin was more effective than with azithromycin or clarithromycin, and doxycycline was more effective than ofloxacin (P<0.05). The mutation rate of resistance genes in children with Mycoplasma pneumoniae pneumonia increased with age (P<0.001). Multivariate logistic regression analysis showed that increased age, extrapulmonary infection, lung consolidation, prolonged fever, prolonged hospitalization, and elevated CRP levels were risk factors for 23SrRNA gene locus mutations (P<0.05). Conclusions Age, extrapulmonary infections, lung consolidation, duration of fever, length of hospitalization, and CRP levels are closely related to 23SrRNA resistance gene locus mutations. Detecting multidrug resistance gene locus mutations in children with Mycoplasma pneumoniae pneumonia can aid in early diagnosis and prediction of treatment efficacy, promoting rational clinical treatment.

Key words： Mycoplasma pneumoniae pneumonia Targeted high-throughput sequencing Multidrug resistance gene locus Child

收稿日期: 2024-07-23

通讯作者: 汪洋，男，主治医师。Email：wyxt1984@126.com。 E-mail: wyxt1984@126.com

作者简介: 张未，女，硕士，主治医师；

引用本文:

张未,汪洋,蔡丽君. 儿童肺炎支原体肺炎多重耐药基因位点突变分析及临床意义[J]. 中国当代儿科杂志, 2024, 26(11): 1176-1181.

ZHANG Wei,WANG Yang,CAI Li-Jun. Analysis of multidrug resistance gene locus mutations and clinical significance in children with Mycoplasma pneumoniae pneumonia[J]. CJCP, 2024, 26(11): 1176-1181.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2407129 或 http://www.zgddek.com/CN/Y2024/V26/I11/1176

	Ojuawo O, Ojuawo A, Aladesanmi A, et al. Childhood pneumonia diagnostics: a narrative review[J]. Expert Rev Respir Med, 2022, 16(7): 775-785. PMID: 35815336. DOI: 10.1080/17476348.2022.2099842.
	Meyer Sauteur PM. Childhood community-acquired pneumonia[J]. Eur J Pediatr, 2024, 183(3): 1129-1136. PMID: 38112800. PMCID: PMC10950989. DOI: 10.1007/s00431-023-05366-6.
	Yadav KK, Awasthi S. Childhood pneumonia: what's unchanged, and what's new?[J]. Indian J Pediatr, 2023, 90(7): 693-699. PMID: 37204597. PMCID: PMC10196299. DOI: 10.1007/s12098-023-04628-3.
	4 徐怀彦, 尚莉丽. 小儿支原体肺炎诊疗研究进展[J]. 中医临床研究, 2021, 13(29): 146-148. DOI: 10.3969/j.issn.1674-7860.2021.29.044.
	5 黄蓉, 段小女, 芮勇宇. 多重耐药弗劳地枸橼酸杆菌的基因组及耐药机制分析[J]. 国际检验医学杂志, 2024, 45(7): 785-789. DOI: 10.3969/j.issn.1673-4130.2024.07.005.
	Dekyi, Xiao Y, Wang X, et al. Predominance of A2063G mutant strains in the Mycoplasma pneumoniae epidemic in children: a clinical and epidemiological study in 2023 in Wuhan, China[J]. Int J Infect Dis, 2024, 145: 107074. PMID: 38734057. DOI: 10.1016/j.ijid.2024.107074.
	7 中华人民共和国国家卫生健康委员会. 儿童肺炎支原体肺炎诊疗指南（2023年版）[J]. 国际流行病学传染病学杂志, 2023, 50(2): 79-85. DOI: 10.3760/cma.j.cn331340-20230217-00023.
	Hu J, Ye Y, Chen X, et al. Insight into the pathogenic mechanism of Mycoplasma pneumoniae[J]. Curr Microbiol, 2022, 80(1): 14. PMID: 36459213.PMCID: PMC9716528. DOI: 10.1007/s00284-022-03103-0.
	Kumar S, Kumar S. Mycoplasma pneumoniae: among the smallest bacterial pathogens with great clinical significance in children[J]. Indian J Med Microbiol, 2023, 46: 100480. PMID: 37741157. DOI: 10.1016/j.ijmmb.2023.100480.
	Liu Y, Zhang R, Yao B, et al. Metagenomics next-generation sequencing provides insights into the causative pathogens from critically ill patients with pneumonia and improves treatment strategies[J]. Front Cell Infect Microbiol, 2023, 12: 1094518. PMID: 36710980.PMCID: PMC9880068. DOI: 10.3389/fcimb.2022.1094518.
	Lin Q, Yao Y, Li X, et al. The application of nanopore targeted sequencing for pathogen diagnosis in bronchoalveolar lavage fluid of patients with pneumonia: a prospective multicenter study[J]. Infect Dis (Lond), 2024, 56(2): 128-137. PMID: 37934028.DOI: 10.1080/23744235.2023.2276785.
	Zhang Z, Dou H, Yuan Q, et al. Proteomic and phenotypic studies of Mycoplasma pneumoniae revealed macrolide-resistant mutation (A2063G) associated changes in protein composition and pathogenicity of type I strains[J]. Microbiol Spectr, 2023, 11(4): e0461322. PMID: 37378520. PMCID: PMC10434051. DOI: 10.1128/spectrum.04613-22.
	Hong JH, Chun JK, Uh Y, et al. Two cases of Mycoplasma pneumoniae pneumonia with A2063G mutation in the 23S rRNA gene in siblings[J]. Ann Lab Med, 2013, 33(1): 65-68. PMID: 23301225. PMCID: PMC3535199. DOI: 10.3343/alm.2013.33.1.65.
	14 吴甜. 云南地区肺炎支原体耐药基因的流行特征及其与基因型相关性研究[D]. 昆明: 昆明理工大学, 2023.
	Lin L, Zhang R, Zhang Z, et al. Clinical value of metagenomics next-generation sequencing in antibiotic resistance of a patient with severe refractory Mycoplasma pneumoniae pneumonia: a case report[J]. Infect Drug Resist, 2023, 16: 4593-4597. PMID: 37465181. PMCID: PMC10351524. DOI: 10.2147/IDR.S419873.
	Wang N, Xu X, Xiao L, et al. Novel mechanisms of macrolide resistance revealed by in vitro selection and genome analysis in Mycoplasma pneumoniae[J]. Front Cell Infect Microbiol, 2023, 13: 1186017. PMID: 37284499. PMCID: PMC10240068. DOI: 10.3389/fcimb.2023.1186017.
	Kim K, Jung S, Kim M, et al. Global trends in the proportion of macrolide-resistant Mycoplasma pneumoniae infections: a systematic review and meta-analysis[J]. JAMA Netw Open, 2022, 5(7): e2220949. PMID: 35816304. PMCID: PMC9274321. DOI: 10.1001/jamanetworkopen.2022.20949.
	Gong C, Huang F, Suo L, et al. Increase of respiratory illnesses among children in Beijing, China, during the autumn and winter of 2023[J]. Euro Surveill, 2024, 29(2): 2300704. PMID: 38214078. PMCID: PMC10785205. DOI: 10.2807/1560-7917.ES.2024.29.2.2300704.
	Tong L, Huang S, Zheng C, et al. Refractory Mycoplasma pneumoniae pneumonia in children: early recognition and management[J]. J Clin Med, 2022, 11(10): 2824. PMID: 35628949. PMCID: PMC9144103. DOI: 10.3390/jcm11102824.
	Miyashita N. Atypical pneumonia: pathophysiology, diagnosis, and treatment[J]. Respir Investig, 2022, 60(1): 56-67. PMID: 34750083. DOI: 10.1016/j.resinv.2021.09.009.
	21 郭步庆, 庞新丰, 乔静, 等. RMPP患儿外周血IL-6、淋巴细胞亚群及23SrRNA基因突变位点A2603G或（和）A2604G检测意义[J]. 检验医学与临床, 2022, 19(1): 19-22. DOI: 10.3969/j.issn.1672-9455.2022.01.006.
	Wang X, Li M, Luo M, et al. Mycoplasma pneumoniae triggers pneumonia epidemic in autumn and winter in Beijing: a multicentre, population-based epidemiological study between 2015 and 2020[J]. Emerg Microbes Infect, 2022, 11(1): 1508-1517. PMID: 35582916. PMCID: PMC9176688. DOI: 10.1080/22221751.2022.2078228.
	Koenen MH, de Groot RCA, de Steenhuijsen Piters WAA, et al. Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiota[J]. EBioMedicine, 2023, 98: 104868. PMID: 37950996. PMCID: PMC10679896. DOI: 10.1016/j.ebiom.2023.104868.