title: Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations.
abstract: Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.|Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, United States of America.|Division of Gastroentero-Hepatology, Department of Internal Medicine, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia.|Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Miftahussurur
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors.forename: Ari Fahrial
authors.initials: AF
authors.lastname: Syam
authors.affiliation: Division of Gastroentero-Hepatology, Department of Internal Medicine, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia.
authors.forename: Iswan Abbas
authors.initials: IA
authors.lastname: Nusi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors.forename: Dadang
authors.initials: D
authors.lastname: Makmun
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.|Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
authors.forename: Langgeng Agung
authors.initials: LA
authors.lastname: Waskito
authors.affiliation: Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, Indonesia.
authors.forename: Lukman Hakim
authors.initials: LH
authors.lastname: Zein
authors.affiliation: Center of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
authors.forename: Fardah
authors.initials: F
authors.lastname: Akil
authors.affiliation: Department of Internal Medicine, Santo Antonius Hospital, Pontianak, Indonesia.
authors.forename: Willy Brodus
authors.initials: WB
authors.lastname: Uwan
authors.affiliation: Department of Internal Medicine, Yowari Hospital, Jayapura, Indonesia.
authors.forename: David
authors.initials: D
authors.lastname: Simanjuntak
authors.affiliation: Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine University of Udayana, Denpasar, Indonesia.
authors.forename: I Dewa Nyoman
authors.initials: ID
authors.lastname: Wibawa
authors.affiliation: Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. RD Kandou Hospital, Manado, Indonesia.
authors.forename: Jimmy Bradley
authors.initials: JB
authors.lastname: Waleleng
authors.affiliation: Department of Internal Medicine, Prof. Dr. W. Z. Johannes General Hospital, Kupang, Indonesia.
authors.forename: Alexander Michael Joseph
authors.initials: AM
authors.lastname: Saudale
authors.affiliation: Division of Gastroentero-hepatology, Department of Internal Medicine, Dr. Zainoel Abidin General Hospital, Banda Aceh, Indonesia.
authors.forename: Fauzi
authors.initials: F
authors.lastname: Yusuf
authors.affiliation: Division of Gastroentero-hepatology, Department of Internal Medicine, Dr. Saiful Anwar General Hospital, Malang, Indonesia.
authors.forename: Syifa
authors.initials: S
authors.lastname: Mustika
authors.affiliation: Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
authors.forename: Pangestu
authors.initials: P
authors.lastname: Adi
authors.affiliation: Division of Gastroentero-Hepatology, Department of Internal Medicine, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia.
authors.forename: Ummi
authors.initials: U
authors.lastname: Maimunah
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors.forename: Hasan
authors.initials: H
authors.lastname: Maulahela
authors.affiliation: Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
authors.forename: Yudith Annisa Ayu
authors.initials: YA
authors.lastname: Rezkitha
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
authors.forename: Phawinee
authors.initials: P
authors.lastname: Subsomwong
authors.affiliation: Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
authors.lastname: Nasronudin
authors.affiliation: Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
authors.forename: Dadik
authors.initials: D
authors.lastname: Rahardjo
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Akada
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.|Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics; D004724:Endoscopy; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D016481:Helicobacter Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D064704:Levofloxacin / Q000627:therapeutic use; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000235:genetics
chemical_list: D012338:RNA, Ribosomal, 23S; D008795:Metronidazole; D064704:Levofloxacin; D000658:Amoxicillin; D017291:Clarithromycin