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台湾实施抗生素消费限制政策后幽门螺杆菌的原发性耐药性及其与毒力因子的关系——一项全国性研究

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

作者信息

Liou Jyh-Ming, Chang Chi-Yang, Chen Mei-Jyh, Chen Chieh-Chang, Fang Yu-Jen, Lee Ji-Yuh, Wu Jeng-Yih, Luo Jiing-Chyuan, Liou Tai-Cherng, Chang Wen-Hsiung, Tseng Cheng-Hao, Wu Chun-Ying, Yang Tsung-Hua, Chang Chun-Chao, Wang Hsiu-Po, Sheu Bor-Shyang, Lin Jaw-Town, Bair Ming-Jong, Wu Ming-Shiang

机构信息

Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Department of Internal Medicine, E- DA Hospital and I-Shou University, Kaohsiung County, Taiwan.

出版信息

PLoS One. 2015 May 5;10(5):e0124199. doi: 10.1371/journal.pone.0124199. eCollection 2015.

Abstract

OBJECTIVE

The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.

METHODS

The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.

RESULTS

The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.

CONCLUSIONS

The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

摘要

目的

台湾政府自2001年起出台政策限制抗菌药物使用。我们旨在评估该政策实施后幽门螺杆菌抗生素消费及主要耐药性的变化,以及毒力因子对耐药性的影响。

方法

使用台湾全民健康保险(NHI)研究数据库分析抗生素的限定日剂量(DDD)。对2000年至2012年间从9家医院分离出的初治幽门螺杆菌菌株(N = 1395)和既往根除治疗失败的菌株(N = 360)进行分析。通过琼脂稀释试验测定最低抑菌浓度。采用PCR方法对CagA和VacA进行基因分型。

结果

大环内酯类抗生素的每日每千人DDD从1997年的1.12降至2008年的0.19,而氟喹诺酮类抗生素的每日每千人DDD从1997年的0.12增至2008年的0.35。阿莫西林、克拉霉素、甲硝唑和四环素的主要耐药率分别维持在2.2%、7.9%、23.7%和1.9%的低水平。然而,左氧氟沙星的主要耐药率从2000 - 2007年的4.9%升至2008 - 2010年的8.3%以及2011 - 2012年的13.4%(p = 0.001)。女性甲硝唑的主要耐药率高于男性(33.1%对18.8%,p < 0.001),这可能归因于硝基咪唑类药物的较高消费量。CagA和VacA均与抗生素耐药性无关。

结论

台湾幽门螺杆菌对克拉霉素和甲硝唑的低主要耐药率可能归因于国家限制抗菌药物使用政策后大环内酯类和硝基咪唑类药物消费量的减少。然而,面对左氧氟沙星耐药性的上升,需要进一步采取策略限制氟喹诺酮类药物的消费。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f1a/4420283/c7aaed19493c/pone.0124199.g001.jpg

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