Trend of changes in antibiotic resistance in Helicobacter pylori from 2013 to 2019: a multicentre report from Taiwan

Background: Antibiotic resistance plays a crucial role in the treatment failure of Helicobacter pylori (H. pylori) infection. This study aimed to determine the trend of changes in the primary, secondary and tertiary antibiotic resistance of H. pylori in Taiwan over the last 7 years. Methods: We retrospectively analysed H. pylori-infected isolates from patients with primary resistance ( n = 1369), secondary resistance ( n = 196) and tertiary resistance ( n = 184) from January 2013 to December 2019. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the Epsilometer test method. Results: A progressively higher primary resistance rate was observed for clarithromycin (11.8–20.4%, p = 0.039 in χ2 test for linear trend), levofloxacin (17.3–38.8%, p < 0.001) and metronidazole (25.6–42.3%, p < 0.001) among naïve patients who received first-line eradication therapy. The dual primary resistance to clarithromycin and metronidazole also progressively increased in a linear trend (2.4–10.4%, p = 0.009). For secondary resistance, an increase was observed for levofloxacin (30.5–64.7%, p = 0.006) and metronidazole (40.5–77.4%, p < 0.001). For tertiary resistance, the observed increase was even more significant for levofloxacin (65.9–100.0%, p = 0.106) and metronidazole (44.4–88.2%, p < 0.001). The resistance to amoxicillin and tetracycline remained very low in Taiwan regardless of primary, secondary and tertiary resistance. Conclusion: Primary, secondary and tertiary antibiotic resistance to clarithromycin, levofloxacin and metronidazole for H. pylori has been increasing in Taiwan since 2013. Treatment should be targeted for eradication success rates of more than 90%. Third-line treatment should be based on antibiotic susceptibility.

Download Full-text

DIFFUSION METHODS FOR CLARITHROMYCIN AND LEVOFLOXACIN SUSCEPTIBILITY TESTING OF HELICOBACTER PYLORI

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2013.6.11 ◽

2014 ◽

pp. 63-70

Author(s):

Trung Nam Phan ◽

Van Huy Tran ◽

Thi Nhu Hoa Tran ◽

Van An Le

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Alternative Therapy ◽

Resistance Rate ◽

Disk Diffusion ◽

Primary Resistance ◽

Secondary Resistance ◽

Central Vietnam ◽

Resistant Strains ◽

H Pylori

Background: The rate of antibiotic resistance in H. pylori is increasing and has become a main cause for failure of treatment. Antibiogram is very important to provide optimal regimens for eradication of H.pylori infected patients. Objective: To determine the resistance prevalence to clarithromycin, levofloxacin of H.pylori strains from patients in Central Vietnam by E-test and disk diffusion isolated, assess the relationship between two diffusion methods. Methods: 56 H.pylori strains were isolated from gastric biopsies of H.pylori infected patients from 7/2012 to 8/2013, of which 13 strains originated from patients in whom eradication of the infection failed after treatment. E-test was used to determine the minimum inhibitory concentrations of clarithromycin (CH) and levofloxacin (LE). Disk diffusion was evaluated as an alternative method to determine susceptibility and compared with the E-test results. Results: In total, the resistant strains (regardless of previous eradication history) to CH, LE were 42,9% and 44,6%, respectively. The ratio of strains with secondary resistance was significantly greater than that of the strains with primary resistance, CH: 84.6% vs. 30.2%, LE: 61.5% vs 39,5% (p < 0.05). The resistance rate to LE in female was significantly higher than in male (p < 0.05). All CH-sensitive strains by E-test had the inhibition diameters of CH was ≥ 24mm and all CH-resistant strains had the inhibition diameters was ≤ 18mm (breakpoint for MIC: 1µg/ml). To LE, the inhibition diameters was ≥ 30mm can determine all LE-sensitive strains and the inhibition diameters was ≤ 26mm can determine all LE-resistant strains by E-test (breakpoint for MIC: 1µg/ml). Conclusions: High resistance rate to CH and LE, suggests that standard CH-based triple therapie may not be useful as the first-line treatment and LE-based triple therapy should not use as an alternative therapy in Central Vietnam. The disk diffusion can use as alternative phenotypic method to determine the susceptbility of H.pylori, which is more practical and inexpensive. Keywords: Helicobacter pylori, levofloxacin, clarithromycin, E-test antibiotic resistance, disk diffusion.

Download Full-text

Antibiotic Resistance of Helicobacter pylori Strains Isolated From Pediatric Patients in Southwest China

Frontiers in Microbiology ◽

10.3389/fmicb.2020.621791 ◽

2021 ◽

Vol 11 ◽

Author(s):

Juan Li ◽

Jianjun Deng ◽

Zhiling Wang ◽

Hong Li ◽

Chaomin Wan

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Pediatric Patients ◽

Southwest China ◽

Pediatric Population ◽

Primary Resistance ◽

Secondary Resistance ◽

Treatment Naïve ◽

H Pylori ◽

Resistance Rates

The number of antibiotics that are appropriate for Helicobacter pylori eradication in children is limited. Profiling regional or population-specific antibiotic resistance is essential in guiding the H. pylori eradication treatment in children. The aim of this study was to evaluate the antibiotic resistance in H. pylori strains isolated from children and adolescents in Southwest China. Gastric biopsies from 157 pediatric patients with or without previous H. pylori eradication treatment were collected for H. pylori culture. Susceptibility to amoxicillin (AML), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET), furazolidone (FZD), and rifampicin (RIF) was determined by E-test or a disk diffusion assay. A total of 87 patients from three ethnic groups (Han/Tibetan/Yi) were H. pylori culture positive (55.4%). The overall resistance rates were 55.2% for CLR, 71.3% for MTZ, 60.9% for RIF, and 18.4% for LEV. No isolate was found to be resistant to AML, TET, and FZD. Among the 53 treatment-naïve pediatric patients, primary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 45.3, 73.6, 15.1, and 60.4%, respectively. Among the 34 treatment-experienced patients, secondary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 70.6, 67.6, 23.5, and 61.8%, respectively. Isolates exhibiting simultaneous resistance to clarithromycin and metronidazole were 28.3 and 52.9% among the treatment-naïve and treatment-experienced patients, respectively. In conclusion, among pediatric patients in Southwest China, resistance rates were high for clarithromycin, metronidazole, levofloxacin, and rifampicin, whereas nil resistance was found to amoxicillin, tetracycline, and furazolidone. Our data suggest that the standard clarithromycin-based triple therapy should be abandoned as empiric therapy, whereas the bismuth quadruple therapy (bismuth/PPI/amoxicillin/tetracycline) would be suitable as first-line empiric treatment regimen for this pediatric population. Tetracycline and furazolidone may be considered for treating refractory H. pylori infections in adolescent patients.

Download Full-text

Helicobacter pylori Eradication Therapy - Recent Trend in Research

The Korean Journal of Helicobacter and Upper Gastrointestinal Research ◽

10.7704/kjhugr.2019.0051 ◽

2020 ◽

Vol 20 (3) ◽

pp. 210-217

Author(s):

Heung Up Kim

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Gastric Mucosa ◽

Drug Exposure ◽

Eradication Therapy ◽

Dual Therapy ◽

Resistance Rate ◽

H Pylori ◽

Selection Of

It is well known that Helicobacter pylori (H. pylori) can cause peptic ulcer, mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, intestinal metaplasia, and ultimately, gastric cancer. Various studies have proven that H. pylori, which attaches to the gastric mucosa, is the cause of gastric cancer and can be eradicated using appropriate antibiotics. Since 2013, Japan has been carrying out national-led eradication treatment of H. pylori for the whole population. However, as drug exposure increases, the resistance rate to some antibiotics increases, and the pattern of antibiotic resistance varies from region to region. Therefore, the development of individualized antimicrobial therapies has become important since antibiotic resistance to H. pylori eradication is a problem worldwide. To help overcome this, remedies such as selection of antibiotics through susceptibility testing, selection of empirical treatment combinations appropriate for the region, dual therapy with high doses of amoxicillin, and the use of rifabutin or sitafloxacin with low antibiotic resistance have been studied. Potassium-competitive acid blocker has been reported to be more potent in inhibiting acid secretion than proton pump inhibitor, and its role in H. pylori eradication is expected. Drug formulations and regimens that are easy to take are being developed to increase compliance. New treatments such as spraying antibiotics directly to the gastric mucosa are being developed and studied.

Download Full-text

E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter Pylori: Importance of the Prevalence of Metronidazole Resistance

10.21203/rs.3.rs-677597/v1 ◽

2021 ◽

Author(s):

Jinnan Chen ◽

Yu Huang ◽

Zhaohui Ding ◽

Xiao Liang ◽

Hong Lu

Keyword(s):

Helicobacter Pylori ◽

Susceptibility Testing ◽

Resistance Rate ◽

Test Method ◽

Major Error ◽

Metronidazole Resistance ◽

Agar Dilution ◽

H Pylori ◽

High Level ◽

Level Resistance

Abstract Background: A number of studies have shown that E-test overestimated the presence of Helicobacter pylori (H. pylori) resistance compared to agar dilution.Objective: The purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.Method: E-test and agar dilution were used to assess susceptibility of H. pylori to metronidazole, clarithromycin and levofloxacin in 281 clinical isolates obtained from China where resistance was high. Cohen kappa analysis, McNemar test, essential and categorical agreement analysis were performed for these two methods. Results: Overall, the result of E-test showed similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement (EA) of E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin were moderate, with 89.0% and 79.7% respectively, but only 45.9% for metronidazole. Results showed categorical agreement (CA) between E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and rate of very major error was 1.8%.Conclusion: E-test can be an alternative method to detect the metronidazole susceptibility of H. pylori in regions where high-level resistance is common.

Download Full-text

Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013–2020: Results of the European Registry on H. pylori Management (Hp-EuReg)

Antibiotics ◽

10.3390/antibiotics10091058 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1058

Author(s):

Luis Bujanda ◽

Olga P. Nyssen ◽

Dino Vaira ◽

Ilaria M. Saracino ◽

Giulia Fiorini ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Resistance Rate ◽

Antimicrobial Susceptibility Testing ◽

Metronidazole Resistance ◽

Infected Adult ◽

H Pylori ◽

European Registry

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013–2016 to 2017–2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013–2016 (33%) and 2017–2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013–2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Download Full-text

Primary antibiotic resistance of Helicobacter pylori among a Chinese Tibetan population

Future Microbiology ◽

10.2217/fmb-2020-0206 ◽

2020 ◽

Vol 15 (14) ◽

pp. 1353-1361

Author(s):

Xiaoqiong Tang ◽

Xiaohong Chen ◽

Yalin Shen ◽

Tiankuo Yang ◽

Renwei Hu ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Primary Resistance ◽

Tibetan Population ◽

Disk Diffusion Assay ◽

Treatment Naïve ◽

Gastric Biopsies ◽

H Pylori ◽

Resistance Rates ◽

Diffusion Assay

Aim: To evaluate the primary antibiotic resistance in Helicobacter pylori strains isolated from a Chinese Tibetan population. Methods & materials: Gastric biopsies from 400 H. pylori treatment-naive Tibetan patients were collected for H. pylori isolation. Susceptibility to amoxicillin (AML)/clarithromycin (CLR)/levofloxacin (LEV)/metronidazole (MTZ)/tetracycline (TET)/rifampicin (RIF)/furazolidone (FZD) was determined by E-test or a disk diffusion assay. Results: Biopsies from 117 patients were H. pylori culture positive (29.3%). The primary resistance rates to MTZ, CLR, LEV, RIF, AML, TET and FZD were 90.6, 44.4, 28.2, 69.2, 7.7, 0.8 and 0.8%, respectively. Interestingly, 42.7% of the strains had simultaneous resistance to CLR and MTZ. Conclusion: Among Tibetan strains, primary resistance rates were high for CLR/MTZ/LEV, whereas primary resistance rates to AML/TET/FZD were low. The high resistance to RIF is a concerning finding.

Download Full-text

Phenotypic and Genotypic Analysis of Resistant Helicobacter pylori Strains Isolated from Children with Gastrointestinal Diseases

Diagnostics ◽

10.3390/diagnostics10100759 ◽

2020 ◽

Vol 10 (10) ◽

pp. 759

Author(s):

Monika Maria Biernat ◽

Aldona Bińkowska ◽

Łukasz Łaczmański ◽

Paweł Biernat ◽

Paweł Krzyżek ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Point Mutations ◽

Gastrointestinal Diseases ◽

Drug Susceptibility Testing ◽

Test Method ◽

Ulcer Disease ◽

Genotypic Analysis ◽

Clinical Diagnoses ◽

H Pylori

Antibiotic resistance of Helicobacter pylori is currently a global issue. The aim of this study was to analyze actual antibiotic resistance rates of H. pylori strains isolated from children with primary infections and to compare the incidence of mutations that determine resistance to clarithromycin (CH) and metronidazole (MET) in children with different clinical diagnoses. A total of 91 H. pylori strains were isolated from 108 children with primary infections. Drug susceptibility testing of the strains was performed using E-test method. Classical sequencing of DNA fragments was used to detect point mutations for CH and MET resistance. Resistance to CH was detected in 31% of isolated strains (28/91), while resistance to MET and CH was detected in 35% (32/91) of strains. A2143G was the most frequently detected mutation and was dominant among strains isolated from children with peptic ulcer disease (80%). Mutations in the rdxA gene were found significantly more frequently among MET-resistant strains than MET-sensitive strains (p = 0.03, Chi2 = 4.3909). In children, a higher frequency of H. pylori multiresistant strains was observed compared with the previous study in the same area. Differences were found in the occurrence of point mutations among H. pylori strains resistant to CH isolated from children with different clinical diagnoses.

Download Full-text

ANTIBIOTIC RESISTANCE SURVEILLANCE OF HELICOBACTER PYLORI AT THE BIOBÍO REGION (CHILE) IN A DECADE

Arquivos de Gastroenterologia ◽

10.1590/s0004-2803.201900000-72 ◽

2019 ◽

Vol 56 (4) ◽

pp. 361-366

Author(s):

Cristian PARRA-SEPÚLVEDA ◽

José S MERINO ◽

Katia SÁEZ-CARRILLO ◽

Carlos GONZÁLEZ ◽

Apolinaria GARCÍA-CANCINO

Keyword(s):

Health Care ◽

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Blood Cells ◽

Eradication Therapy ◽

Clarithromycin Resistance ◽

Resistant Strains ◽

H Pylori ◽

Horse Red Blood Cells ◽

Co2 Atmosphere

ABSTRACT BACKGROUND: Helicobacter pylori infection in Chile remains as a public and private health-care system’s challenge, with a prevalence of the infection over 70%. Nowadays, antibiotic treatment of the infection is mandatory to prevent the arising of severe associated diseases but failures in the eradication therapy mainly due to clarithromycin resistance has been observed worldwide and first line eradication therapy seems to be not effective anymore in several geographical areas. Thus, health-care systems are committed to maintain an epidemiological surveillance upon the evolution of the antibiotic resistance of this priority 2 pathogen. OBJECTIVE: This work reports a 10 years surveillance of the primary antibiotic resistance of H. pylori clinical isolates at the Biobío region-Chile, and the evolution of resistance toward amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline among the species. METHODS: H. pylori strains were investigated during the periods 2005-2007 (1435 patients analysed) and 2015-2017 (220 patients analysed) by inoculating a saline homogenate biopsy onto the surface of Columbia agar (Oxoid, Basingstoke, UK) - supplemented with 7% horse red blood cells plus DENT inhibitor (Oxoid, Basingstoke, UK) - following by incubation at 37ºC under 10% CO2 atmosphere for five days. Antibiotic resistance pattern of the isolates was assessed using the disk diffusion test in Müeller-Hinton agar supplemented with 7% horse red blood cells followed by incubation for further three days under 10% CO2 atmosphere. Statistical analysis was done using the SPSS v22 software and P values <0.05 were considered statistically significant. RESULTS: A total of 41% of 1435 patients were detected to be infected with H. pylori by bacteriological culture in 2005-2007 period, meanwhile 32.7% from 220 patients were also infected in 2015-2017 period. The clinical isolates of H. pylori are mostly susceptible to amoxicillin and tetracycline (both over 98% of strains), but less susceptible to levofloxacin in both periods analysed (over 79% of the strains). On the other hand, metronidazole continuous showing the highest score of resistant isolates (over 40% of resistant strains), although an 18% fewer resistant strains were observed in 2015-2017 period. Clarithromycin, the key antibiotic in eradication therapies, has an increased frequency of resistant strain isolated in the decade (22.5% in 2005-2007 and 29.2% in 2015-2017). Multidrug resistant strains (two, three and four antibiotics) were also detected in both periods with the highest scores for simultaneous resistance to clarithromycin-metronidazole (18%) and clarithromycin-metronidazole-levofloxacin (12.5%) resistant strains. According to gender, the isolates resistant to amoxicillin, clarithromycin and metronidazole were more frequent in female, with a specific increment in amoxicillin and clarithromycin resistance. CONCLUSION: The frequency of clarithromycin resistance (29.2%) detected in 2015-2017 suggests that conventional triple therapy is no longer effective in this region.

Download Full-text

Treatment of Helicobacter pylori infections in the light of the increase of antibiotic resistance

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0011.6469 ◽

2018 ◽

Vol 72 ◽

pp. 143-158

Author(s):

Eliza Mnich ◽

Jakub Ibran ◽

Magdalena Chmiela

Keyword(s):

Fatty Acids ◽

Ascorbic Acid ◽

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Eradication Therapy ◽

The World ◽

Potential Alternative ◽

Resistant Strains ◽

Treatment Mechanisms ◽

H Pylori

The aim of this study was to present the risks associated with the occurrence of Helicobacter pylori (H. pylori) infection in humans and the problems related to eradication procedures with the use of antibiotic treatment. The content provides an overview of the available methods of infection diagnosis and recommended therapeutic schemes as well as potential alternative schedules of treatment. Mechanisms of H. pylori resistance to commonly used antibiotics including the mutations in the genome leading to resistance and the incidence of resistant strains in the world has been described. Finally, we introduced substances with some potential in eradication therapy, including probiotics, plant formulations as well as polyunsaturated fatty acids and ascorbic acid.

Download Full-text

Antibiotic Resistance of Helicobacter Pylori and Influencing Factors in Yangzhou, China: a Cross-sectional Study

10.21203/rs.3.rs-198405/v1 ◽

2021 ◽

Author(s):

Yun Zhang ◽

Xinyi Feng ◽

Lijun Bian ◽

Yan Zhang ◽

Qian Li ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Gastrointestinal Symptoms ◽

Cross Sectional Study ◽

Resistance Rate ◽

Resistance Pattern ◽

Cross Sectional ◽

Chip Technology ◽

Resistance Patterns ◽

H Pylori

Abstract Background: The Helicobacter pylori (H. pylori) antibiotic resistance pattern differs geographically, knowledge of local antimicrobial resistance pattern is key to successful eradication. The current study was performed to investigate the resistance of H. pylori to 5 commonly used antibiotics in Yangzhou.Methods: A total of 461 H. pylori strains were collected from April 2018 to September 2019 in Yangzhou and tested for their susceptibility to clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline using gene chip technology.Results: The resistance rates of H. pylori to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline were 41.0%, 44.9%, 38.8%, 6.3% and 1.1%. In addition, sixteen multiple resistance patterns were detected, and fortunately there were no strains resistant to all five antibiotics. The vacA s1 allele was detected in each strain, 64.0% of the isolates were s1/m2 genotype, 36.0% s1/m1 genotype. In multivariate analysis, history of chronic superficial gastritis was significantly associated with clarithromycin resistance, strains isolated from subjects with gastrointestinal symptoms had a significantly higher likelihood of metronidazole resistance, and antibiotic resistance of H. pylori was independent of both sex and age.Conclusion: The resistance rate of H. pylori to clarithromycin, levofloxacin and metronidazole were very high in Yangzhou, the results will help in selecting effective eradication regimens.

Download Full-text