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肺炎支原体感染儿童接受大环内酯类药物治疗后大环内酯类耐药相关突变的发生情况。

Development of macrolide resistance-associated mutations after macrolide treatment in children infected with Mycoplasma pneumoniae.

作者信息

Suzuki Yu, Shimotai Yoshitaka, Itagaki Tsutomu, Seto Junji, Ikeda Tatsuya, Yahagi Kazue, Mizuta Katsumi, Hongo Seiji, Matsuzaki Yoko

机构信息

Department of Microbiology, Yamagata Prefectural Institute of Public Health, Yamagata 990-0031, Japan.

Department of Infectious Diseases, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan.

出版信息

J Med Microbiol. 2017 Nov;66(11):1531-1538. doi: 10.1099/jmm.0.000582. Epub 2017 Oct 6.

Abstract

PURPOSE

To determine the timing of the emergence of macrolide-resistant mutations after macrolide treatment in individuals with Mycoplasma pneumoniae infections.

METHODOLOGY

Between October 2011 and December 2013, serial pharyngeal swab specimens were collected before and after macrolide treatment from 21 otherwise healthy children infected with M. pneumoniae without macrolide-resistant mutations. The copy numbers of a M. pneumoniae gene and the proportion of clones showing macrolide-resistance mutations were determined for each specimen.

RESULTS

After macrolide treatment (10-15 mg kg day clarithromycin for 5-10 days or 10 mg kg day azithromycin for 3 days), fever resolved in 19 (90 %) of 21 children within 1 to 2 days, and the M. pneumoniae gene copy number decreased in all but one specimen in the second set of specimens relative to the number in the corresponding initial specimens. None of the second specimens, which were collected 2-4 days after initiation of macrolide treatment, showed mutations in the 23S rRNA gene. However, the proportion of mutant clones with A2063G and A2064G mutations in the specimens collected 7-24 days after initiation of treatment increased to 100 %. We identified a family in which three members had M. pneumoniae infections. The analysis of transmission in this household indicated that the M. pneumoniae harbouring a macrolide-resistant mutation that developed in the index patient after macrolide treatment was not transmitted to the family members.

CONCLUSION

A macrolide-resistant population might develop in individual patients up to 24 days after initiation of macrolide treatment. However, the decrease in M. pneumoniae load after macrolide administration effectively reduces interpersonal transmission.

摘要

目的

确定肺炎支原体感染个体在接受大环内酯类药物治疗后出现大环内酯类耐药突变的时间。

方法

在2011年10月至2013年12月期间,从21名无大环内酯类耐药突变的肺炎支原体感染的健康儿童中,在大环内酯类药物治疗前后采集系列咽拭子标本。测定每个标本中肺炎支原体基因的拷贝数以及显示大环内酯类耐药突变的克隆比例。

结果

在接受大环内酯类药物治疗(10 - 15mg/kg/天克拉霉素,持续5 - 10天或10mg/kg/天阿奇霉素,持续3天)后,21名儿童中有19名(90%)在1至2天内体温恢复正常,相对于相应初始标本中的数量,第二组标本中除一个标本外,其余所有标本中的肺炎支原体基因拷贝数均下降。在大环内酯类药物治疗开始后2 - 4天采集的第二组标本中,均未显示23S rRNA基因发生突变。然而,在治疗开始后7 - 24天采集的标本中,具有A2063G和A2064G突变的突变克隆比例增至100%。我们发现一个家庭中有三名成员感染了肺炎支原体。该家庭中的传播分析表明,在指数患者接受大环内酯类药物治疗后出现的携带大环内酯类耐药突变的肺炎支原体未传播给家庭成员。

结论

在大环内酯类药物治疗开始后长达24天,个体患者可能会出现大环内酯类耐药菌群体。然而,大环内酯类药物给药后肺炎支原体载量的下降有效减少了人际传播。

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