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

doi:10.7499/j.issn.1008-8830.2104033

Abstract
Figure/Table
References(18)
Related Citation (15)
Read Tracking
Download Tracking

Download: PDF (1288 KB) HTML()
Export: BibTeX | EndNote (RIS) Supporting Info

Abstract Objective To study the drug resistance of Mycoplasma pneumoniae (MP) in the bronchoalveolar lavage fluid (BALF) of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and the distribution of drug-resistance genes, as well as the association of alleles at 2063 locus of 23SrRNA V region central ring with resistance to antimicrobial drugs. Methods BALF specimens were collected from 245 children with RMPP who were admitted to the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2020. A rapid cultured drug sensitivity assay was used to detect the resistance of MP isolates to nine commonly used antimicrobial drugs. The real-time PCR was used to measure MP DNA. The direct sequencing was used to detect gene mutations in MP 23SrRNA V region central ring. Results Among the 245 BALF specimens, 207 tested positive for MP DNA, with a positive rate of 84.5%. The results of drug susceptibility test showed that the children with RMPP had a resistance rate of > 70% to macrolide antimicrobial drugs, with the highest resistance rate to clarithromycin, followed by roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin, and these children had a resistance rate of < 5% to quinolone antimicrobial drugs. Among the 207 MP DNA-positive specimens, 41 (19.8%) had no drug-resistance gene mutations and 166 (80.2%) had drug-resistance gene mutations, among which 154 (74.4%) had an A→G mutation at 2063 locus of 23SrRNA V region central ring, 7 (3.4%) had an A→G mutation at 2064 locus, and 5 (2.4%) had mutations in both 2063 and 2064 loci. Among the 166 specimens with point mutations of the MP 23SrRNA gene, 159 (95.8%) had point mutations at 2063 locus. The A→G point mutation at 2063 locus of 23SrRNA V region central ring had a great impact on resistance to macrolide antimicrobial drugs. There was a significant difference in the distribution of alleles at 2063 locus between the children with resistance to clarithromycin, roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin (P < 0.05). Conclusions MP in the BALF of children with RMPP has a relatively high resistance rate to macrolide antimicrobial drugs. Resistance to macrolide antimicrobial drugs is closely associated with the A→G point mutation in the 23SrRNA gene, and the point mutation at 2063 locus of 23SrRNA V region central ring may affect the drug-resistance mechanism of MP.

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	CHEN Dan
	ZHANG Na-Li
	ZHANG Ting
	SUN Xiao-Min

Key words： Refractory Mycoplasma pneumoniae pneumonia Bronchoalveolar lavage fluid Mycoplasma pneumoniae Drug resistance Child

Received: 08 April 2021

Cite this article:

CHEN Dan,ZHANG Na-Li,ZHANG Ting et al. Detection of drug-resistance genes of Mycoplasma pneumoniae in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia[J]. CJCP, 2021, 23(7): 707-712.

URL:

http://www.zgddek.com/EN/10.7499/j.issn.1008-8830.2104033 OR http://www.zgddek.com/EN/Y2021/V23/I7/707

[1]	郭亚琳, 杨玉霞, 董芃芃. 下呼吸道感染患儿支气管肺泡灌洗液的病原学研究[J]. 中国当代儿科杂志, 2019, 21(2):144-149. DOI:10.7499/j.issn.1008-8830.2019.02.007. PMID:30782276. PMCID:PMC7389829.
[2]	Ha SG, Oh KJ, Ko KP, et al. Therapeutic efficacy and safety of prolonged macrolide, corticosteroid, doxycycline, and levofloxacin against macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children[J]. J Korean Med Sci, 2018, 33(43):e268. DOI:10.3346/jkms.2018.33.e268. PMID:30344461. PMCID:PMC6193889.
[3]	Zhang C, Zhang Q, Du JL, et al. Correlation between the clinical severity, bacterial load, and inflammatory reaction in children with Mycoplasma pneumoniae pneumonia[J]. Curr Med Sci, 2020, 40(5):822-828. DOI:10.1007/s11596-020-2261-6. PMID:33123897. PMCID:PMC7595045.
[4]	Rivaya B, Jordana-Lluch E, Fernández-Rivas G, et al. Macrolide resistance and molecular typing of Mycoplasma pneumoniae infections during a 4 year period in Spain[J]. J Antimicrob Chemother, 2020, 75(10):2752-2759. DOI:10.1093/jac/dkaa256. PMID:32653897. PMCID:PMC7678890.
[5]	Wagner K, Imkamp F, Pires VP, et al. Evaluation of lightmix mycoplasma macrolide assay for detection of macrolide-resistant Mycoplasma pneumoniae in pneumonia patients[J]. Clin Microbiol Infect, 2019, 25(3):383.e5-383.e7. DOI:10.1016/j.cmi.2018.10.006. PMID:30391582.
[6]	Lu CY, Yen TY, Chang LY, et al. Multiple-locus variable-number tandem-repeat analysis (MLVA) of macrolide-susceptible and -resistant Mycoplasma pneumoniae in children in Taiwan[J]. J Formos Med Assoc, 2020, 119(10):1539-1545. DOI:10.1016/j.jfma.2019.12.008. PMID:31924377.
[7]	中华医学会儿科学分会呼吸学组, 《中华实用儿科临床杂志》编辑委员会. 儿童肺炎支原体肺炎诊治专家共识(2015年版)[J]. 中华实用儿科临床杂志, 2015, 30(17):1304-1308. DOI:10.3760/cma.j.issn.2095-428X.2015.17.006.
[8]	中华医学会儿科学分会呼吸学组儿科支气管镜协作组. 儿科支气管镜术指南(2009年版)[J]. 中华儿科杂志, 2009, 47(10):740-744. DOI:10.3760/cma.j.issn.0578-1310.2009.10.006. PMID:20021807.
[9]	Noori Goodarzi N, Pourmand MR, Arfaatabar M, et al. First detection and characterization of macrolide-resistant Mycoplasma pneumoniae from people with community-acquired pneumonia in Iran[J]. Microb Drug Resist, 2020, 26(3):245-250. DOI:10.1089/mdr.2019.0223. PMID:31545147.
[10]	Zhang YY, Zhou YL, Li SX, et al. The clinical characteristics and predictors of refractory Mycoplasma pneumoniae pneumonia in children[J]. PLoS One, 2016, 11(5):e0156465. DOI:10.1371/journal.pone.0156465. PMID:27227519.
[11]	Zhou ZB, Li XZ, Chen XJ, et al. Macrolide-resistant Mycoplasma pneumoniae in adults in Zhejiang, China[J]. Antimicrob Agents Chemother, 2015, 59(2):1048-1051. DOI:10.1128/AAC.04308-14. PMID:25451048. PMCID:PMC4882022.
[12]	姜越, 刘禧杰, 秦选光, 等. 2011年北京地区儿童肺炎支原体耐药情况及其耐药机制研究[J]. 中国全科医学, 2013, 16(11B):3778-3782. DOI:10.3969/j.issn.1007-9572.2013.32.005.
[13]	Ma ZY, Zheng YJ, Deng JK, et al. Characterization of macrolide resistance of Mycoplasma pneumoniae in children in Shenzhen, China[J]. Pediatr Pulmonol, 2014, 49(7):695-700. DOI:10.1002/ppul.22851. PMID:23861188.
[14]	Bébéar C, Pereyre S, Peuchant O. Mycoplasma pneumoniae:susceptibility and resistance to antibiotics[J]. Future Microbiol, 2011, 6(4):423-431. DOI:10.2217/fmb.11.18. PMID:21526943.
[15]	Kinnear A, McAllister TA, Zaheer R, et al. Investigation of macrolide resistance genotypes in Mycoplasma bovis isolates from Canadian feedlot cattle[J]. Pathogens, 2020, 9(8):622. DOI:10.3390/pathogens9080622. PMID:32751555. PMCID:PMC7459582.
[16]	姚慧生, 张睿, 刘立云, 等. 肺炎支原体耐药基因检测与难治性肺炎支原体肺炎的相关性分析[J]. 国际儿科学杂志, 2016, 43(6):492-496. DOI:10.3760/cma.j.issn.1673-4408.2016.06.017.
[17]	郑玥, 刘秀芬, 刘朝阳. 儿童难治性支原体肺炎感染诊治中MP-DNA载量及耐药检测的意义分析[J]. 临床肺科杂志, 2020, 25(8):1149-1154. DOI:10.3969/j.issn.1009-6663.2020.08.004.
[18]	Yuan C, Min FM, Ling YJ, et al. Clinical characteristics and antibiotic resistance of Mycoplasma pneumoniae pneumonia in hospitalized Chinese children[J]. Comb Chem High Throughput Screen, 2018, 21(10):749-754. DOI:10.2174/1386207322666190111112946. PMID:30636596.