大环内酯类耐药的儿童难治性肺炎支原体肺炎临床特征分析

doi:10.19871/j.cnki.xfcrbzz.2024.06.008

摘要/Abstract

摘要： 目的通过观察大环内酯类耐药的肺炎支原体（macrolide-resistant Mycoplasma pneumoniae,MRMP）感染所致儿童难治性肺炎支原体肺炎（refractory Mycoplasma pneumoniae pneumonia,RMPP）的临床特征,以探讨其在儿童RMPP及时诊治中的临床意义。方法回顾性分析2022年1月至2023年12月在海南省妇女儿童医学中心住院的1226例RMPP患儿的临床资料。对患儿进行纤维支气管镜检查和支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）检查,提取BALF中的MRMP-DNA,检测其23S rRNA V区突变位点,并根据检测结果,分为大环内酯类耐药组和对照组（非大环内酯类耐药）。结果共计1226例RMPP患儿,其中对照组357例,大环内酯类耐药组869例。大环内酯类耐药组的平均年龄[（6.12±2.98）岁]高于对照组[（2.82±2.19）岁]（P<0.001）。大环内酯类耐药组的发热时长[（6.61±1.77）d]高于对照组[（5.33±1.09）d]（P<0.001）。大环内酯类耐药组RMPP患儿的白细胞（white blood cell count,WBC）、中性粒细胞百分比（percentage of neutrophil,NE%）、超敏C反应蛋白（high sensitive C-reactive protein,hs-CRP）、乳酸脱氢酶（lactate dehydrogenase,LDH）及白细胞介素-6（interleukin-6,IL-6）水平均高于对照组（均P<0.05）;大环内酯类耐药组重症MPP（severe MPP,SMPP）/危重症MPP（fulminant MPP,FMPP）、肺外并发症、严重黏膜病变（糜烂、溃疡或坏死）、支气管内塑形性栓子、胸腔积液及坏死性肺炎的发生率均高于对照组（均P<0.05）。大环内酯类耐药组RMPP患儿的平均住院日[（6.59±1.63）d]高于对照组[（5.32±1.38）d]（P<0.001）。结论 MRMP感染所导致的RMPP患儿的临床表现更为严重,其发热时间、住院时间更长,炎症反应更重,肺内、外并发症更多。对RMPP患儿及时实施纤维支气管镜检查,并采集BALF样本进行检测,对指导临床正确诊治有重要参考价值。

关键词: 肺炎支原体, 耐大环内酯, 基因突变, 难治性支原体肺炎, 支气管肺泡灌洗液, 纤维支气管镜检查

Abstract: Objective Via observing the clinical characteristics of refractory Mycoplasma pneumoniae pneumonia (RMPP) caused by macrolide-resistant Mycoplasma pneumoniae (MRMP) infection in children, to explore its clinical significance in the timely diagnosis and treatment of children with RMPP. Method The clinical data of 1226 hospitalized children with RMPP from January 2022 to December 2023 in the Hainan Women and Children's Medical Center were analyzed retrospectively. Bronchoscopy and bronchoalveolar lavage fluid (BALF) were performed on each subject and MRMP-DNA in the BALF were taken to detect the 23S rRNA V region mutation sites. Children with RMPP were divided into macrolide-resistant group and control group (non-macrolide-resistant group) depending on the gene detection results. Result A total of 1226 children with RMPP were recruited, including 869 cases in the macrolide-resistant group and 357 cases in the control group. Among them, there were 369 males (51.7%) and 555 females (48.3%). The average age in the macrolide-resistant group [(6.12±2.98) y] was higher than that in the control group [(2.82±2.19) y] (P<0.001). The fever time in the macrolide-resistant group [(6.61±1.77) d] was longer than that in the control group [(5.33±1.09) d] (P<0.001). Compared with the children with RMPP in the control group, the values of white blood cell count(WBC), percentage of neutrophil (NE%), high sensitive C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and interleukin-6 (IL-6) were higher in the macrolide-resistant group, the differences were statistically significant (P<0.05); Compared with the children with RMPP in the control group, the incidences of severe MPP (SMPP)/fulminant MPP (FMPP), extra-pulmonary complications, severe mucosal lesions(erosion, ulcer or necrosis), endotracheal plastic phlegm plug, pleural effusion and necrotic pneumonic were higher in the macrolide-resistant group, the differences were statistically significant (P<0.05). The average hospitalization day in the macrolide-resistant group [(6.59±1.63) d] was longer than that in the control group [(5.32±1.38) d] (P<0.001). Conclusion The clinical manifestations of RMPP children caused by MRMP infection were more serious, with longer fever time, longer hospital stay, more severe inflammatory reaction and more intrapulmonary and extrapulmonary complications. Timely implementing bronchoscopy in children with RMPP and collecting BALF samples for testing may have important values for guiding the correct clinical diagnosis and treatment.

Key words: Mycoplasma pneumonia, Macrolides resistant, Gene mutation, Refractory mycoplasma pneumoniae pneumonia, Bronchoalveolar lavage fluid, Fiberoptic bronchoscopy

中图分类号:

郑君, 吴琪晔, 曾霞, 张笃飞. 大环内酯类耐药的儿童难治性肺炎支原体肺炎临床特征分析[J]. 新发传染病电子杂志, 2024, 9(6): 42-47.

Zheng Jun, Wu Qiyue, Zeng Xia, Zhang Dufei. Analysis of clinical characteristics of refractory Mycoplasma pneumoniae in macrolide-resistant children[J]. Electronic Journal of Emerging Infectious Diseases, 2024, 9(6): 42-47.

参考文献

[1] SONG Z, JIA G, LUO G, et al.Global research trends of Mycoplasma pneumoniae pneumonia in children: a bibliometric analysis[J]. Front Pediatr, 2023, 11: 1306234.
[2] 鲍汝英, 徐国成. 儿童难治性肺炎支原体肺炎的发病机制及治疗进展[J]. 齐齐哈尔医学院学报, 2022, 43(13): 1274-1278.
[3] 吴琰, 魏会平, 曹欣等. 儿童下呼吸道肺炎支原体感染流行特点分析[J/CD]. 新发传染病电子杂志, 2021, 6(4): 336-338.
[4] ZHAN XW, DENG LP, WANG ZY, et al.Correlation between Mycoplasma pneumoniae drug resistance and clinical characteristics in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia[J]. Ital J Pediatr, 2022, 48(1):190.
[5] 陈丹, 张娜丽, 张婷等. 难治性肺炎支原体肺炎患儿支气管肺泡灌洗液中肺炎支原体耐药基因检测分析[J]. 中国当代儿科杂志, 2021, 23(7): 707-712.
[6] 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/CD].新发传染病电子杂志,2024,9(1):73-79
[7] 刘金荣, 刘立雍, 赵顺英, 等. 咽拭子与支气管肺泡灌洗液荧光定量PCR检测儿童肺炎支原体感染分析[J]. 疾病监测, 2019, 34(5):389-393.
[8] 吕亚奇, 冯国双. 医学研究中常见的样本量估算方法[J]. 慢性病学杂志, 2016(4): 359-361.
[9] 国家卫生健康委员会人才交流服务中心儿科呼吸内镜诊疗技术专家组, 中国医师协会儿科医师分会内镜专业委员会, 中国医师协会内镜医师分会儿科呼吸内镜专业委员会, 等. 中国儿科可弯曲支气管镜术指南(2018年版)[J]. 中华实用儿科临床杂志, 2018, 33(13): 983-989.
[10] 李小明, 雷智贤, 谢蔓芳, 等. 2014年海口地区呼吸道感染患儿肺炎支原体感染状况分析[J]. 重庆医学, 2017, 46(12): 1657-1658.
[11] LENG M, YANG J, ZHOU J.The molecular characteristics, diagnosis, and treatment of macrolide-resistant Mycoplasma pneumoniae in children[J]. Front Pediatr, 2023, 11:1115009.
[12] EDELSTEIN IA, IVANOVA OV, ROMASHOV OI, et al.Course of Lower Respiratory Tract Infection in Young People Treated at the Military Hospital of Smolensk Garrison with Detected Mycoplasma pneumoniae Carrying a Macrolide-Resistant Mutation in 23S rRNA Gene[J]. Pathogens, 2023, 12(1):103.
[13] 席少婷. 儿童难治性肺炎支原体肺炎诊治进展[J]. 国际儿科学杂志, 2020, 47(6): 384-388.
[14] 宋均亚, 李季阳, 梁学超, 等. 中国儿童难治性支原体肺炎主要危险因素的Meta分析[J]. 山东医药, 2019, 59(11): 59-63.
[15] 张伟利, 张新星, 顾文婧, 等. 肺炎支原体耐药在难治性肺炎支原体肺炎患儿发病中的作用[J]. 中华实用儿科临床杂志, 2021, 36(11): 822-826.
[16] JIN HL, ZHAN L, MEI SF, et al.Serum Cytokines and FeNO in School-Aged Children with Mycoplasma pneumoniae Pneumonia[J]. Med Sci Monit, 2020, 26: e923449.
[17] XIN D, MI Z, HAN X, et al.Molecular mechanisms of macrolide resistance in clinical isolates of Mycoplasma pneumoniae from China[J]. Antimicrob Agents Chemother, 2009, 53(5): 2158-2159.
[18] 王广洋. 血清HMGB1、IL-4、IL-6、IFN-γ对难治性肺炎支原体肺炎患儿发生肺外并发症的预测价值[J]. 现代实用医学, 2023, 35(12): 1668-1670.
[19] 马瑞, 裴亮. 儿童难治性肺炎支原体肺炎早期临床预测因素[J]. 中国医科大学学报, 2023, 52(11):1015-1017,1024.
[20] YANG B, ZHANG W, GU W, et al.Differences of clinical features and prognosis between Mycoplasma pneumoniae necrotizing pneumonia and non-Mycoplasma pneumoniae necrotizing pneumonia in children[J]. BMC Infect Dis, 2021, 21(1):797.
[21] 张雅静, 孟晨. 儿童难治性肺炎患儿肺炎支原体大环内酯类耐药基因突变分析[J]. 中国实用儿科杂志, 2023,38(5): 376-380.
[22] 吴琰, 魏会平, 曹欣等. N-乙酰半胱氨酸雾化辅助治疗小儿下呼吸道肺炎支原体感染的临床疗效及对炎症因子水平的影响[J/CD]. 新发传染病电子杂志, 2021, 6(2): 105-108.
[23] WANG C, SONG C, LIU G.Mycoplasma pneumoniae and Recurrent Respiratory Tract Infection Within One Year After Treatment in Infants: Risk Factors and Prevalence[J]. Iran J Pediatr, 2021, 31(4): e112283.
[24] 韩茜, 蒋凯旋, 王燕侠, 等. 儿童难治性支原体肺炎危险因素的系统评价[J]. 中国循证医学杂志, 2021, 21(10): 1168-1173.
[25] 宁阳. 小儿难治性肺炎支原体肺炎的临床特点及影响因素分析[J]. 当代医学, 2021, 27(24): 170-171.
[26] 黎耀文, 林洁琼, 范绮梦, 等. 2023年儿童重症肺炎支原体肺炎所致坏死性肺炎危险因素分析[J/CD]. 新发传染病电子杂志, 2024, 9(1): 1-6.
[27] BERLUCCHI M, PELUCCHI F, TIMPANO S, et al.A conservative treatment for plastic bronchitis in pediatric age[J]. Am J Otolaryngol, 2014, 35(2): 204-206.
[28] 牟丹丹, 崔拓, 李威, 等. 儿童肺炎支原体肺炎并呼吸道黏液栓形成的早期预测指标[J]. 中华实用儿科临床杂志, 2018, 33(10): 758-762.
[29] 李慧敏,宁晶晶,李志梅,等. 纤维支气管镜肺泡灌洗治疗肺炎患儿的临床分析[J]. 中国社区医师, 2022, 38(31): 41-43.
[30] 马晓林,丁臻博, 黄永坤. 儿童肺炎支原体对大环内酯类抗生素耐药现状及机制研究进展[J]. 国际药学研究杂志, 2020, 47(10): 804-808.