Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

Muhammad Miftahussurur and Pradeep Krishna Shrestha and Phawinee Subsomwong and Rabi Prakash Sharma and Yoshio Yamaoka (2016) Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal. BMC Microbiology, 16 (1). pp. 1-10. ISSN 14712180

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Abstract

Background: The prevalence of Helicobacter pylori antibiotic susceptibility in the Nepalese strains is untracked. We determined the antibiotic susceptibility for H. pylori and analyzed the presence of genetic mutations associated with antibiotic resistance in Nepalese strains. Results: This study included 146 consecutive patients who underwent gastroduodenal endoscopy in Kathmandu, Nepal. Among 42 isolated H. pylori, there was no resistance to amoxicillin and tetracycline. In contrast, similar with typical South Asian patterns; metronidazole resistance rate in Nepalese strains were extremely high (88.1 , 37/42). Clarithromycin resistance rate in Nepalese strains were modestly high (21.4 , 9/42). Most of metronidazole resistant strains had highly distributed rdxA and frxA mutations, but were relative coincidence without a synergistic effect to increase the minimum inhibitory concentration (MIC). Among strains with the high MIC, 63.6 (7/11) were associated with frameshift mutation at position 18 of frxA with or without rdxA involvement. However, based on next generation sequencing data we found that one strain with the highest MIC value had a novel mutation in the form of amino acid substituted at Ala-212, Gln-382, Ile-485 of dppA and Leu-145, Thr-168, Glu-117, Val-121, Arg-221 in dapF aside from missense mutations in full-length rdxA. Mutations at Asn-87 and/or Asp-91 of the gyrA were predominantly in levofloxacin-resistant strains. The gyrB mutation had steady relationship with the gyrA 87-91 mutations. Although three (44.4 ) and two (22.2 ) of clarithromycin resistant strains had point mutation on A2143G and A2146G, we confirmed the involvement of rpl22 and infB in high MIC strains without an 23SrRNA mutation. Conclusions: The rates of resistance to clarithromycin, metronidazole and levofloxacin were high in Nepalese strains, indicating that these antibiotics-based triple therapies are not useful as first-line treatment in Nepal. Bismuth or non-bismuth-based quadruple regimens, furazolidone-based triple therapy or rifabutin-based triple therapy may become alternative strategy in Nepal. © 2016 The Author(s).

Item Type: Article
Uncontrolled Keywords: amoxicillin; clarithromycin; DNA topoisomerase (ATP hydrolysing) A; levofloxacin; metronidazole; RNA 23S; tetracycline; amoxicillin; antiinfective agent; bacterial DNA; bacterial protein; clarithromycin; DNA topoisomerase (ATP hydrolysing); initiation factor 2; levofloxacin; metronidazole; nitroreductase; RdxA protein, Helicobacter pylori; RNA 23S; tetracycline, adolescent; adult; aged; amino acid substitution; antibiotic resistance; antibiotic sensitivity; Article; bacterial gene; bacterial strain; controlled study; female; frameshift mutation; frxA gene; gastrointestinal endoscopy; gene mutation; gyrA gene; Helicobacter pylori; human; infB gene; major clinical study; male; middle aged; minimum inhibitory concentration; missense mutation; Nepalese; next generation sequencing; nonhuman; point mutation; rdxA gene; rpl22 gene; antibiotic resistance; drug effects; endoscopy; genetics; Helicobacter Infections; Helicobacter pylori; high throughput sequencing; isolation and purification; microbial sensitivity test; microbiology; mutation; Nepal; nucleotide sequence; pathogenicity; prevalence; procedures; young adult, Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Clarithromycin; DNA Gyrase; DNA, Bacterial; Drug Resistance, Bacterial; Endoscopy; Female; Genes, Bacterial; Helicobacter Infections; Helicobacter pylori; High-Throughput Nucleotide Sequencing; Humans; Levofloxacin; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Mutation; Nepal; Nitroreductases; Point Mutation; Prevalence; Prokaryotic Initiation Factor-2; RNA, Ribosomal, 23S; Tetracycline; Young Adult
Subjects: R Medicine
R Medicine > R Medicine (General) > R735-854 Medical education. Medical schools. Research
Divisions: Artikel Ilmiah > SCOPUS INDEXED JOURNAL
Creators:
CreatorsNIM
Muhammad MiftahussururNIDN0029097909
Pradeep Krishna ShresthaUNSPECIFIED
Phawinee SubsomwongUNSPECIFIED
Rabi Prakash SharmaUNSPECIFIED
Yoshio YamaokaUNSPECIFIED
Depositing User: PPJPI
Date Deposited: 30 Sep 2020 05:58
Last Modified: 30 Sep 2020 06:01
URI: http://repository.unair.ac.id/id/eprint/94606
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