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Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of Helicobacter pylori in Mongolia.

ABSTRACT: Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia were considered. Minimal inhibitory concentrations for two fluoroquinolones (ciprofloxacin and moxifloxacin), rifabutin, and furazolidone were determined via two-fold agar dilution. Genomic mutations in antibiotic-resistant strains were identified by next-generation sequencing using the Illumina Miseq platform and compared with genes from a reference H. pylori strain (26695). The resistance rate of H. pylori strains to quinolones was high (44% to ciprofloxacin and 42% to moxifloxacin), and resistance to rifabutin was low (0.5%); none were resistant to furazolidone. Most quinolone-resistant strains possessed gyrA gene mutations causing amino acid changes (e.g., N87K, A88P, and D91G/Y/N). While one rifabutin-resistant strain had amino acid-substituting mutations in rpoB (D530N and R701C), the other had three novel rpoB mutations; both rifabutin-resistant strains were sensitive to furazolidone. Overall, our findings suggest that rifabutin and/or furazolidone may be an alternative, effective H. pylori treatment in patients who have failed to respond to other treatment regimens.

SUBMITTER: Khangai A

PROVIDER: S-EPMC10745380 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of Helicobacter pylori in Mongolia.

Khangai Ayush A Saruuljavkhlan Batsaikhan B Azzaya Dashdorj D Gantuya Boldbaatar B Oyuntsetseg Khasag K Akada Junko J Matsumoto Takashi T Yamaoka Yoshio Y

Microorganisms 20231124 12

Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia w ...[more]

PMID: 38137996

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Project description:BackgroundThe emergence of multidrug-resistant Helicobacter pylori has undermined eradication strategies to prevent the development of gastric cancer. This study was conducted to estimate the prevalence of secondary antibiotic resistance of H. pylori in urban multicultural areas in Malaysia.MethodsFrom January 2017 to December 2021, gastric biopsies from 218 patients with a history of H. pylori eradication failure were sent to our laboratory for antibiotic susceptibility testing. A minimal inhibitory concentration was determined for six antibiotics, namely metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline, and rifampicin using the E-test method. Two multidrug-resistant H. pylori strains identified in this study were subjected to whole genome sequencing.ResultsEradication failure was observed to be significantly higher in the Malaysian Chinese patients than in the Malaysian Indian and Malay patients. H. pylori were successfully isolated from 51 patients (23.4%). Overall, the antibiotic resistance rates of H. pylori to metronidazole, clarithromycin, levofloxacin, and amoxicillin were 82.4% (42/51), 72.5% (37/51), 52.9% (27/51), and 3.9% (2/51), respectively. Resistance to tetracycline and rifampicin were not observed during the study period. Resistance to more than one antibiotic was observed in 82.4% (42/51) of the isolates, of which 42.2% (19/42) were resistant to three antibiotic classes. Resistance to both clarithromycin and metronidazole were most frequently observed in isolates with dual resistance (56.5%; 13/23). Codon substitutions in penicillin-binding protein 1A (V346L, V374L, G595_V596InsG, Y604H, and N608S) were detected in amoxicillin-resistance H. pylori strains. Herein, we report amoxicillin resistance in H. pylori isolated from Malaysian patients, and its resistance mechanism, for the first time.ConclusionOur results show the increase trend in secondary multidrug resistance in H. pylori isolates, which warrants continuous surveillance.

Project description:AimTo investigate the resistance of Helicobacter pylori (H. pylori) to ciprofloxacin (CIP), levofloxacin (LVX) and moxifloxacin (MOX) in the Beijing area and to elucidate the resistance mechanisms.MethodsSeventy-nine H. pylori clinical strains, isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009, were tested for their susceptibility to CIP, LVX and MOX using the E-test method. H. pylori strain 26695 was included in the susceptibility testing as a control strain. According to the minimal inhibitory concentration (MIC) values, a strain was classified as resistant to CIP, LVX or MOX when the MIC was > 1 microg/mL. We amplified by polymerase chain reaction (PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H. pylori strains selected at random.ResultsIn this study, the resistance rates of H. pylori to CIP, LVX or MOX were 55.7% (44/79), and the primary resistance rates were 26.6% (21/79). Patients with secondary resistance had received LVX in previous eradication treatments, but not MOX or CIP. Forty-five strains, including 29 CIP, LVX or MOX-resistant strains (MIC: 1.5-32 microg/mL) and 16 susceptible strains, were selected randomly from the 79 strains and used in PCR analysis. Among these 45 strains, 27 resistant strains had mutations in the gyrA gene, including 11 strains with mutations corresponding to Asp-91 (MIC: 2-32 microg/mL), one of which also had a mutation corresponding to Val-150, and 16 strains had mutations at Asn-87 (MIC: 4-32 microg/mL), three of which also had mutations corresponding to Arg-140 or Val-150. In addition, Arg-140, Val-150 or Ala-97 mutations were separately detected in three susceptible strains. Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation. There was a significant difference in the occurrence of mutations in the gyrA gene between CIP, LVX and MOX-resistant and -susceptible strains (P < 0.05), but 2 resistant strains were found to possess no quinolone resistance-determining region mutations.ConclusionResistance is primarily mediated through point mutations in gyrA. Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.

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Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of Helicobacter pylori in Mongolia.

Publications

Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of <i>Helicobacter pylori</i> in Mongolia.

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