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

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

  • Infect Drug Resist. 2019 Jan 31;12:345-358. doi: 10.2147/IDR.S187063.
Muhammad Miftahussurur 1 2,  Langgeng Agung Waskito 2 3,  Ari Fahrial Syam 4,  Iswan Abbas Nusi 1,  Gontar Siregar 5,  Marselino Richardo 6,  Achmad Fuad Bakry 7,  Yudith Annisa Ayu Rezkitha 2 8,  I Dewa Nyoman Wibawa 9,  Yoshio Yamaoka 3 10 11
Affiliations

Affiliations

  • 1 Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia, muhammad-m@fk.unair.ac.id.
  • 2 Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia, muhammad-m@fk.unair.ac.id.
  • 3 Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Japan, yyamaoka@oita-u.ac.jp.
  • 4 Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia.
  • 5 Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan 20136, Indonesia.
  • 6 Department of Internal Medicine, Merauke City General Hospital, Merauke 99656, Indonesia.
  • 7 Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Sriwijaya University, Palembang 30126, Indonesia.
  • 8 Department of Internal Medicine, Muhammadiyah University of Surabaya, Surabaya 60113, Indonesia.
  • 9 Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Udayana, Denpasar 80232, Indonesia.
  • 10 Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA, yyamaoka@oita-u.ac.jp.
  • 11 Global Oita Medical Advanced Research Center for Health, Yufu 879-5593, Japan, yyamaoka@oita-u.ac.jp.
PMID: 30774400 DOI: 10.2147/IDR.S187063
Abstract

Background: The prevalence of Helicobacter pylori 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 H. pylori (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 H. pylori infections in vitro. 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 gyrA and gyrB 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 rpoB point mutations. There was an association between vacA genotypes of H. pylori and rifaximin resistance (P = 0.048).

Conclusion: furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate H. pylori 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.

Keywords

Helicobacter pylori; Indonesia; antibiotics; drug resistance.

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