|
1
|
Tong Y, Dang R, Yin Y, Men C, Xi R. A whole genome sequencing-based assay to investigate antibiotic susceptibility and strain lineage of Helicobacter pylori. Microb Pathog 2024; 197:107069. [PMID: 39490594 DOI: 10.1016/j.micpath.2024.107069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 10/08/2024] [Accepted: 10/21/2024] [Indexed: 11/05/2024]
Abstract
Helicobacter pylori (H. pylori) antibiotic resistance has been widespread and increasing worldwide, which presented a significant challenge to the successful eradication of H. pylori infection. Identification of antibiotic resistance and exploration of potential resistance mechanisms are thus necessary for effective treatment. For this purpose, we herein develop a whole genome sequencing (WGS) assay based on next-generation sequencing (NGS) to detect the entire genome of 73 H. pylori strains isolated from gastric mucosa of patients in Tianjin, China, and analyzed the association between single-nucleotide polymorphism (SNP) in resistance-related genes and phenotypic sensitivity. We discovered the consistent relationship between genotypic and phenotypic resistance by A2143C/G in 23S rRNA for clarithromycin (Kappa: 0.882), N87K/I in gyrA for levofloxacin (Kappa: 0.883), and wild-type of pbp1 for amoxicillin. In addition, we obtained 4 super-resistant clinical strains of H. pylori, which formed thick, sticky biofilms, were extremely resistant to all antibiotics regardless of the present of mutations in antibiotic targets sites. Therefore, biofilm formation is also a mechanism of drug resistance, and biofilm-related proteins or genes are also expected to be used as screening markers for H. pylori resistance.
Collapse
Affiliation(s)
- Yue Tong
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tongyan Road, Haihe Education Park, Tianjin 300350, China
| | - Ruoyu Dang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tongyan Road, Haihe Education Park, Tianjin 300350, China
| | - Yongmei Yin
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tongyan Road, Haihe Education Park, Tianjin 300350, China.
| | - Changjun Men
- Tianjin First Central Hospital, No. 24, Fukang Road, Nankai District, Tianjin 300190, China.
| | - Rimo Xi
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tongyan Road, Haihe Education Park, Tianjin 300350, China.
| |
Collapse
|
|
2
|
Hasanuzzaman M, Bang CS, Gong EJ. Antibiotic Resistance of Helicobacter pylori: Mechanisms and Clinical Implications. J Korean Med Sci 2024; 39:e44. [PMID: 38288543 PMCID: PMC10825452 DOI: 10.3346/jkms.2024.39.e44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
Helicobacter pylori is a pathogenic bacterium associated with various gastrointestinal diseases, including chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The increasing rates of H. pylori antibiotic resistance and the emergence of multidrug-resistant strains pose significant challenges to its treatment. This comprehensive review explores the mechanisms underlying the resistance of H. pylori to commonly used antibiotics and the clinical implications of antibiotic resistance. Additionally, potential strategies for overcoming antibiotic resistance are discussed. These approaches aim to improve the treatment outcomes of H. pylori infections while minimizing the development of antibiotic resistance. The continuous evolution of treatment perspectives and ongoing research in this field are crucial for effectively combating this challenging infection.
Collapse
Affiliation(s)
- Md Hasanuzzaman
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
| |
Collapse
|
|
3
|
Li CL, Zhou K, Zhang YX, Suo BJ, Tian XL, Zhang YX, Ren XL, Shi YY, Zhou LY, Song ZQ. Tailored therapy guided by genotypic resistance of clarithromycin and levofloxacin detected by polymerase chain reaction in the first-line treatment of Helicobacter pylori infection. J Dig Dis 2024; 25:36-43. [PMID: 38323705 DOI: 10.1111/1751-2980.13250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/28/2023] [Accepted: 01/08/2024] [Indexed: 02/08/2024]
Abstract
OBJECTIVES We aimed to explore the efficacy and safety of tailored therapy guided by genotypic resistance in the first-line treatment of Helicobacter pylori (H. pylori) infection in treatment-naive patients. METHODS Gastric mucosal specimens were taken during gastroscopy, and main mutations of clarithromycin- and levofloxacin-resistant genes were detected by polymerase chain reaction (PCR). Sensitive antibiotics were selected individually for treating H. pylori infection with tailored bismuth-containing quadruple therapy (BQT) consisting of esomeprazole 20 mg twice daily, bismuth potassium citrate 220 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, or levofloxacin 500 mg once daily, or metronidazole 400 mg four times daily. Safety and patient compliance were assessed 1-3 days after eradication. Treatment outcome was evaluated by urea breath test 4-8 weeks after eradication. RESULTS One hundred and thirty-two treatment-naive patients with H. pylori infection were included. PCR results suggested resistance rates of 47.7% and 34.9% for clarithromycin and levofloxacin, respectively, and a dual resistance rate of 18.2%. Eradication rates of tailored BQT were 87.1% and 95.8% by intention-to-treat (ITT) analysis and per-protocol (PP) analysis, respectively. There was no statistically significant difference in the efficacy of 7-day clarithromycin-containing, 7-day levofloxacin-containing, and 14-day full-dose metronidazole-containing BQT (ITT analysis: P = 0.488; PP analysis: P = 0.833). The incidence of adverse events was 19.7%, and patient compliance was 97.7%. CONCLUSION Tailored BQT guided by genotypic resistance can achieve satisfactory efficacy, safety, and patient compliance in the first-line treatment of H. pylori infection.
Collapse
Affiliation(s)
- Cai Ling Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Kai Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yue Xi Zhang
- Department of Gastroenterology, Beijing No. 6 Hospital, Beijing, China
| | - Bao Jun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xue Li Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yu Xin Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xin Lu Ren
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yan Yan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Li Ya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zhi Qiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| |
Collapse
|
|
4
|
Cho SH, Park MS, Park SY, Kim DH, You HS, Kim HS. Effectiveness of 7-day triple therapy with half-dose clarithromycin for the eradication of Helicobacter pylori without the A2143G and A2142G point mutations of the 23S rRNA gene in a high clarithromycin resistance area. Front Med (Lausanne) 2023; 10:1150396. [PMID: 37035320 PMCID: PMC10073449 DOI: 10.3389/fmed.2023.1150396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 02/27/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND Tailored therapy has been widely used for patients with Helicobacter pylori (H. pylori) infection in South Korea. Herein, we evaluated the treatment outcomes of tailored clarithromycin-based triple therapy (TT) in patients infected with H. pylori. METHODS We enrolled 460 patients without A2142G and A2143G point mutations by dual priming oligonucleotide-based polymerase chain reaction who had taken TT and undergone the urease breath test to evaluate eradication in clinical practice. Eradication rates according to the treatment duration and dose of clarithromycin were analyzed. RESULTS Among 460 patients (164 women, median age 63.0 years), 250 patients underwent TT with full-dose clarithromycin (TT-full CLA), and 216 patients underwent TT with half-dose clarithromycin (TT-half CLA). The eradication rates were 88.0% (220/250) in patients with TT-full CLA and 85.2% (179/210) in patients with TT-half CLA. In 250 patients with TT-full CLA, the eradication rates were 86.8% (33/38) in patients with 7-day TT-full CLA and 88.2% (187/212) in patients with 10-day or 14-day TT-full CLA (P = 0.788). In 210 patients with TT-half CLA, the eradication rates were 84.2% (139/165) in those with a 7-day TT-half CLA and 88.9% (40/45) in those with a 10-day or 14-day TT-half CLA (P = 0.436). CONCLUSION For patients with H. pylori infection without A2142G and A2143G point mutations by DPO-PCR in clinical practice, treatment extension above 7-day TT with full CLA did not improve the eradication rates. Future studies on the treatment outcomes of TT-half CLA considering effectiveness and compliance are warranted.
Collapse
Affiliation(s)
| | | | - Seon-Young Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
| | | | | | | |
Collapse
|
|
5
|
Gong L, El-Omar EM. Application of molecular techniques in Helicobacter pylori detection: limitations and improvements. Helicobacter 2021; 26:e12841. [PMID: 34333819 DOI: 10.1111/hel.12841] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/02/2021] [Accepted: 07/02/2021] [Indexed: 12/13/2022]
Affiliation(s)
- Lan Gong
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Emad M El-Omar
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| |
Collapse
|
|
6
|
Tshibangu-Kabamba E, Yamaoka Y. Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications. Nat Rev Gastroenterol Hepatol 2021; 18:613-629. [PMID: 34002081 DOI: 10.1038/s41575-021-00449-x] [Citation(s) in RCA: 269] [Impact Index Per Article: 67.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been intensively studied and are discussed in this Review. Three profiles of resistance - single drug resistance, multidrug resistance and heteroresistance - seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.
Collapse
Affiliation(s)
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan. .,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.
| |
Collapse
|
|
7
|
Efficacy of Loop-Mediated Isothermal Amplification for H. pylori Detection as Point-of-Care Testing by Noninvasive Sampling. Diagnostics (Basel) 2021; 11:diagnostics11091538. [PMID: 34573879 PMCID: PMC8467764 DOI: 10.3390/diagnostics11091538] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/17/2021] [Accepted: 08/21/2021] [Indexed: 11/23/2022] Open
Abstract
For targeted eradication of Helicobacterpylori (H. pylori) to reduce gastric cancer burden, a convenient approach is definitely needed. The purpose of this study was to evaluate the LAMP assay for H. pylori detection using samples collected by noninvasive and self-sampling methods. The available LAMP assay for H. pylori detection was appraised and verified using reference and clinically isolated H. pylori strains. In addition, a clinical study was conducted to assess the LAMP assay on 51 patients, from whom saliva, oral brushing samples, feces, corpus, and antrum specimens were available. Clarithromycin resistance was also analysed through detection of A2143G mutation using the LAMP-RFLP method. The validation and verification analysis demonstrated that the LAMP assay had an acceptable result in terms of specificity, sensitivity, reproducibility, and accuracy for clinical settings. The LAMP assay showed a detection limit for H. pylori down to 0.25 fg/µL of genomic DNA. An acceptable consensus was observed using saliva samples (sensitivity 58.1%, specificity 84.2%, PPV 85.7%, NPV 55.2%, accuracy 68%) in comparison to biopsy sampling as the gold standard. The performance testing of different combinations of noninvasive sampling methods demonstrated that a combination of saliva and oral brushing could achieve a sensitivity of 74.2% and a specificity of 57.9%. A2143G mutation detection by LAMP-RFLP showed perfect consensus with Sanger sequencing results. It appears that the LAMP assay in combination with noninvasive and self-sampling as a point-of-care testing (POCT) approach has potential usefulness to detect H.pylori infection in clinic settings and screening programs.
Collapse
|
|
8
|
Zhang C, Cao M, Lv T, Wang H, Liu X, Xie Y, Lv N, Chen H, Cram DS, Zhong J, Zhou L. Molecular testing for H. pylori clarithromycin and quinolone resistance: a prospective Chinese study. Eur J Clin Microbiol Infect Dis 2021; 40:1599-1608. [PMID: 33646449 DOI: 10.1007/s10096-021-04188-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 02/07/2021] [Indexed: 11/24/2022]
Abstract
In China, there is a high prevalence of antibiotic-resistant Helicobacter pylori infections in the population. The aim of the study was to assess a new ARMS-PCR test for detection of H. pylori clarithromycin resistance (CR) and quinolone resistance (QR) mutations and evaluate the spectrum of antibiotic resistance in patients from three Chinese provinces. Sanger sequencing and multiplex ARMS-PCR were used to detect H. pylori CR and QR bacteria in gastric biopsy samples. Among the 1,182 patients enrolled with gastritis, 643 (54.4%) were positive for H. pylori. Of these, 371 (57.7%) had antibiotic-resistant strains, comprising 236 (63.6%) with a single drug antibiotic-resistant strain and 135 (36.4%) with multiple drug-resistant strains. Following Sanger sequencing analysis of 23S rRNA and gyrA gene for mutations (antibiotic resistance markers), rates of CR, QR, and multidrug resistance (CR and QR) were 19.9, 12.0, and 25.8%, respectively. The 23S rRNA CR mutation A2143G (286, 96.9%) and the gyrA QR mutations C261A (85, 31.5%) and G271A (71, 26.3%) were common. Benchmarking against Sanger sequencing results, multiplex ARMS-PCR test had a high diagnostic sensitivity and specificity for detection of CR (96 and 93%), QR (95 and 92%) and multidrug resistance (95 and 95%). Based on our findings, the high incidence of single and multiple antibiotic resistance requires the routine checking of antibiotic resistance in all patients with suspected H. pylori infections. Multiplex ARMS-PCR is a simple and rapid test that can be now used for more efficient treatment of H. pylori infections and reduces the misuse of antibiotics.
Collapse
Affiliation(s)
- Chuanfeng Zhang
- Department of Biochemistry, Department of the Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Mengjiao Cao
- Department of Biochemistry, Department of the Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Tangshan Lv
- Zhejiang Mole Biological Technology Co., Ltd, Hangzhou, China
| | - Hongyan Wang
- Zhejiang Mole Biological Technology Co., Ltd, Hangzhou, China
| | - Xiaoxiao Liu
- Zhejiang Mole Biological Technology Co., Ltd, Hangzhou, China
| | - Yong Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Nonghua Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Hongtan Chen
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - David S Cram
- Department of Biochemistry, Department of the Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Zhong
- Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, 313000, China.
| | - Linfu Zhou
- Department of Biochemistry, Department of the Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China.
| |
Collapse
|