Emergence of amoxicillin resistance and identification of novel mutations of the pbp1A gene in Helicobacter pylori in Vietnam.

BACKGROUND: Amoxicillin-resistant Helicobacter pylori (H. pylori) strains seem to have increased over time in Vietnam. This threatens the effectiveness of H. pylori eradication therapies with this antibiotic. This study aimed to investigate the prevalence of primary resistance of H. pylori to amoxicillin and to assess its association with pbp1A point mutations in Vietnamese patients. MATERIALS AND METHODS: Naive patients who presented with dyspepsia undergoing upper gastrointestinal endoscopy were recruited. Rapid urease tests and PCR assays were used to diagnose H. pylori infection. Amoxicillin susceptibility was examined by E-tests. Molecular detection of the mutant pbp1A gene conferring amoxicillin resistance was carried out by real-time PCR followed by direct sequencing of the PCR products. Phylogenetic analyses were performed using the Tamura-Nei genetic distance model and the neighbor-joining tree building method. RESULTS: There were 308 patients (46.1% men and 53.9% women, p = 0.190) with H. pylori infection. The mean age of the patients was 40.5 ± 11.4 years, ranging from 18 to 74 years old. The E-test was used to determine the susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 0.125 µg/ml) in 101 isolates, among which the rate of primarily resistant strains to amoxicillin was 25.7%. Then, 270 sequences of pbp1A gene fragments were analysed. There were 77 amino acid substitution positions investigated, spanning amino acids 310-596, with the proportion varying from 0.4 to 100%. Seven amino acid changes were significantly different between amoxicillin-sensitive (AmoxS) and amoxicillin-resistant (AmoxR) samples, including Phe366 to Leu (p <  0.001), Ser414 to Arg (p <  0.001), Glu/Asn464-465 (p = 0.009), Val469 to Met (p = 0.021), Phe473 to Val (p <  0.001), Asp479 to Glu (p = 0.044), and Ser/Ala/Gly595-596 (p = 0.001). Phylogenetic analyses suggested that other molecular mechanisms might contribute to amoxicillin resistance in H. pylori in addition to the alterations in PBP1A. CONCLUSIONS: We reported the emergence of amoxicillin-resistant Helicobacter pylori strains in Vietnam and new mutations statistically associated with this antimicrobial resistance. Additional studies are necessary to identify the mechanisms contributing to this resistance in Vietnam.

Vietnam Association of Gastroenterology (VNAGE) consensus on the management of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is prevalent and has a rapidly increasing antibiotic resistance rate in Vietnam. Reinfection is quite common, and gastric carcinoma remains one of the most common malignancies, which is not uncommon to develop after successful eradication. The purpose of this consensus is to provide updated recommendations on the management of H. pylori infection in the country. The consensus panel consisted of 32 experts from 14 major universities and institutions in Vietnam who were invited to review the evidence and develop the statements using the Delphi method. The process followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The consensus level was defined as ≥80% for agreement on the proposed statements. Due to the limited availability of high-quality local evidence, this consensus was also based on high-quality evidence from international studies, especially those conducted in other populations in the Asia-Pacific region. The panel finally reached a consensus on 27 statements after two voting rounds, which consisted of four sections (1) indications for testing and selection of diagnostic tests (2), treatment regimens, (3) post-treatment confirmation of H. pylori status, and (4) reinfection prevention methods and follow-up after eradication. Important issues that require further evidence include studies on third-line regimens, strategies to prevent H. pylori reinfection, and post-eradication follow-up for precancerous gastric lesions. We hope this consensus will help guide the current clinical practice in Vietnam and promote multicenter studies in the country and international collaborations.