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针对印度尼西亚甲硝唑和左氧氟沙星耐药率高的地区感染的替代根除方案。

Alternative eradication regimens for infection in Indonesian regions with high metronidazole and levofloxacin resistance.

作者信息

Miftahussurur Muhammad, Waskito Langgeng Agung, Syam Ari Fahrial, Nusi Iswan Abbas, Siregar Gontar, Richardo Marselino, Bakry Achmad Fuad, Rezkitha Yudith Annisa Ayu, Wibawa I Dewa Nyoman, Yamaoka Yoshio

机构信息

Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia,

Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia,

出版信息

Infect Drug Resist. 2019 Jan 31;12:345-358. doi: 10.2147/IDR.S187063. eCollection 2019.

Abstract

BACKGROUND

The prevalence of resistance to metronidazole and clarithromycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens.

METHODS

We determined the minimum inhibitory concentrations (MICs) of five alternative antibiotics for (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using the agar dilution method and assessed mutations associated with antibiotic resistance using next-generation sequencing.

RESULT

Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9% and 6.7%, respectively). The strains isolated from patients on Java Island had the highest resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which the resistance rate was 38.9%, the other four antibiotics could be successfully employed to eradicate levofloxacin- and metronidazole-resistant infections in . Interestingly, garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative antibiotic in regions with high clarithromycin resistance. There was an inconsistent association between and mutations and garenoxacin resistance. We confirmed that the I837V (replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were the predominant point mutations. There was an association between genotypes of and rifaximin resistance ( = 0.048).

CONCLUSION

furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate in Indonesia, including regions with high metronidazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should be considered for eradication of levofloxacin-resistant strains.

摘要

背景

在印度尼西亚,对甲硝唑和克拉霉素耐药的情况很普遍。此外,在印度尼西亚,在未使用铋剂治疗的情况下左氧氟沙星耐药率不断上升,这导致使用其他抗生素作为替代方案。

方法

我们使用琼脂稀释法测定了五种替代抗生素(利福昔明、利福布汀、呋喃唑酮、加替沙星和西他沙星)的最低抑菌浓度(MICs),并使用下一代测序评估与抗生素耐药相关的突变。

结果

对从1039名成年消化不良患者中分离出的106株菌株进行分析发现,没有菌株对呋喃唑酮耐药。所有菌株对利福布汀和西他沙星也敏感。相比之下,对利福昔明和加替沙星的耐药率较高(分别为38.9%和6.7%)。从爪哇岛患者中分离出的菌株对加替沙星和利福昔明的耐药率最高。此外,耐药情况在不同种族中分布均匀,介于25.0%至69.2%之间。除利福昔明耐药率为38.9%外,其他四种抗生素可成功用于根除印度尼西亚耐左氧氟沙星和甲硝唑的幽门螺杆菌感染。有趣的是,在巴厘岛和巴布亚岛等克拉霉素耐药率高的地区发现了对加替沙星敏感的菌株。相比之下,在克拉霉素耐药率高的地区,利福昔明可能不被视为替代抗生素。加替沙星耐药与幽门螺杆菌和23S rRNA突变之间存在不一致的关联。我们证实I837V(837位异亮氨酸被缬氨酸取代)、A2414T/V、Q2079K和K2068R是幽门螺杆菌主要的23S rRNA点突变。幽门螺杆菌的23S rRNA基因型与利福昔明耐药之间存在关联(P = 0.048)。

结论

基于呋喃唑酮、利福布汀和西他沙星的疗法可被视为在印度尼西亚根除幽门螺杆菌的替代方案,包括甲硝唑和克拉霉素耐药率高的地区。此外,对于根除耐左氧氟沙星菌株,应考虑使用西他沙星而非加替沙星。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4457/6362932/f68660e2ef8d/idr-12-345Fig1.jpg

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