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Helicobacter pylori Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance.

ABSTRACT: BACKGROUND/AIMS:Clarithromycin resistance in Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. We investigated the point mutations in the 23S rRNA genes of patients with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the point mutations. METHODS:A total of 431 adult patients with H. pylori infection were recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for seven days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for seven days. H. pylori eradication rates were compared. RESULTS:Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C). The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The overall H. pylori eradication rate was 83.7%, and the seven-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the seven-day PAC-treated nonresistance group (ITT; 55.4% (51/92) vs. 74.3% (252/339), p = 0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), p = 0.0001). CONCLUSIONS:There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori when treated with PAM for seven days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.

SUBMITTER: Seo SI

PROVIDER: S-EPMC7019680 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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<i>Helicobacter pylori</i> Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance.

Seo Seung In SI Do Byoung Joo BJ Kang Jin Gu JG Kim Hyoung Su HS Jang Myoung Kuk MK Kim Hak Yang HY Shin Woon Geon WG

Journal of clinical medicine 20191225 1

<h4>Background/aims</h4>Clarithromycin resistance in <i>Helicobacter pylori</i> is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. We investigated the point mutations in the 23S rRNA genes of patients with clarithromycin-resistant <i>H. pylori</i> and compared the <i>H. pylori</i> eradication rates based on the point mutations.<h4>Methods</h4>A total of 431 adult patients with <i>H. pylori</i> infection were recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Pati ...[more]

PMID: 31881688

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Project description:BackgroundClarithromycin (CLR) is the most commonly recommended antibiotic in Helicobacter pylori eradication regimens, but the prevalence of CLR-resistant H. pylori is increasing. CLR resistance is associated with mutations in the 23S rRNA gene. However, H. pylori eradication can still be achieved with triple therapy, and an additive effect may occur with multiple antibiotics.MethodsTwenty-six CLR-resistant strains were examined. The MIC of clarithromycin was determined by agar-dilution-testing on Columbia agar, as described elsewhere. The conserved region of the H. pylori 23S rRNA gene between nucleotide positions 1445 and 2846 [GenBank: U27270] was amplified. RFLP and sequence analysis were performed with the 1402-bp PCR product. Synergy between clarithromycin and amoxicillin was assessed using the agar dilution checkerboard technique. To confirm the correlation between mutation and synergistic effect with subinhibitory concentrations of AMX, site-directed mutagenesis was performed in four CLR-susceptible H. pylori isolates.ResultsTwenty-six clarithromycin-resistant strains were examined. The conserved region of the H. pylori 23S rRNA gene was amplified, and the purified PCR product was checked for mutations by restriction fragment length polymorphism (RFLP) analysis and sequencing. A synergistic effect was found in only three of the 12 H. pylori strains (25%) with the A2142G mutation and five of the 10 H. pylori strains (50%) with the A2143G mutation (fractional inhibitory concentration: FIC < 0.5, minimal inhibitory concentration: MIC<2 mg/L) was found. Site-directed mutagenesis was performed in four CLR-susceptible H. pylori isolates.Three of these isolates harboring a mutation in position A2143G grew under selection with CLR (MIC >16 mg/L), and all three strains showed the synergistic effect (FIC<0.5). In contrast, three of the same four strains transformed with DNA fragments with a mutation in position A2142G were resistant to CLR (MIC>16 mg/L) and showed no synergism with amoxicillin (FIC>2).ConclusionsHere we demonstrate that in 100% of the in vitro transformed strains, a mutation at position A2143G leads to a synergistic effect between clarithromycin and amoxicillin, whereas a mutation at position at A2142G had no discernible effect.

Dataset Information

Helicobacter pylori Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance.

Publications

<i>Helicobacter pylori</i> Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance.

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