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中国儿童菌株中与克拉霉素、甲硝唑和左氧氟沙星耐药相关的抗生素靶基因的突变

Mutations in the Antibiotic Target Genes Related to Clarithromycin, Metronidazole and Levofloxacin Resistance in Strains from Children in China.

作者信息

Zhang Yanyi, Wen Yi, Xiao Qiulin, Zheng Wei, Long Gao, Chen Bo, Shu Xiaoli, Jiang Mizu

机构信息

Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People's Republic of China.

出版信息

Infect Drug Resist. 2020 Jan 30;13:311-322. doi: 10.2147/IDR.S235615. eCollection 2020.

Abstract

PURPOSE

This study aimed to characterize common mutations of antibiotic-resistant gene of clarithromycin, metronidazole and levofloxacin in () and determine their association with antibiotic resistance of for providing a strategy for eradication therapy of infection in children.

PATIENTS AND METHODS

The antibiotic resistance to clarithromycin, metronidazole and levofloxacin for strains isolated from children was determined by E-test. The mutation of domain V of 23S rRNA, and and genes was performed by PCR-based sequencing of DNA fragments.

RESULTS

Out of the 79 strains examined, 66 (83.5%) were resistant to at least one of the tested antibiotics and 13 (16.5%) were fully sensitive. A total of 29 (36.7%) strains were resistant to clarithromycin. Analysis of the 23S rRNA gene showed that most mutations occurred at the A2143G and T2182C sites, showing a frequency of 82.8% (24/29) and 89.7% (26/29) respectively. In the 11 sensitive strains to clarithromycin, the frequency of A2143G mutation was only 45.5%, which was significantly lower than that in resistant strains (P<0.05). There were 54 strains (68.4%) resistant to metronidazole, with most mutations occurring at G47A and T184G in the gene. T184G mutation was recognized in metronidazole-sensitive strains, but no G47A mutation was identified. Twelve strains (15.2%) were resistant to levofloxacin. Position 91 mutation of the gene occurred only in resistant strains, whereas position 87 mutations were detected in both sensitive and resistant strains to levofloxacin.

CONCLUSION

In resistant strains isolated from children in China, most mutations occurred at A2143G of the 23S rRNA gene for clarithromycin; G47A mutation of gene for metronidazole; and at 91 mutation of gene for levofloxacin. It is suggested that susceptibility testing together with screening the mutation of antimicrobial-resistant gene prior to treatment is important for the eradication of in children.

摘要

目的

本研究旨在对从儿童中分离出的幽门螺杆菌(Helicobacter pylori,Hp)中克拉霉素、甲硝唑和左氧氟沙星耐药基因的常见突变进行特征分析,并确定它们与Hp抗生素耐药性的关联,以为儿童Hp感染的根除治疗提供策略。

患者与方法

采用E-test法测定从儿童中分离出的79株Hp菌株对克拉霉素、甲硝唑和左氧氟沙星的抗生素耐药性。通过基于聚合酶链反应(PCR)的DNA片段测序对23S rRNA、rrl、rpoB和gyrA基因的V结构域进行突变检测。

结果

在检测的79株Hp菌株中,66株(83.5%)对至少一种受试抗生素耐药,13株(16.5%)完全敏感。共有29株(36.7%)菌株对克拉霉素耐药。对23S rRNA基因的分析表明,大多数突变发生在A2143G和T2182C位点,频率分别为82.8%(24/29)和89.7%(26/29)。在对克拉霉素敏感的11株菌株中,A2143G突变的频率仅为45.5%,显著低于耐药菌株(P<0.05)。有54株(68.4%)菌株对甲硝唑耐药,大多数突变发生在rrl基因的G47A和T184G位点。在对甲硝唑敏感的菌株中发现了T184G突变,但未发现G47A突变。12株(15.2%)菌株对左氧氟沙星耐药。gyrA基因的91位突变仅发生在耐药菌株中,而87位突变在对左氧氟沙星敏感和耐药的菌株中均有检测到。

结论

在中国儿童分离出的Hp耐药菌株中,克拉霉素耐药主要发生在23S rRNA基因的A2143G位点;甲硝唑耐药主要发生在rrl基因的G47A位点;左氧氟沙星耐药主要发生在gyrA基因的91位。建议在治疗前进行药敏试验并筛查抗菌耐药基因突变对于儿童Hp根除至关重要。

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