scholarly journals Trends in Secondary Antibiotic Resistance of Helicobacter pylori from 2007 to 2014: Has the Tide Turned?

2014 ◽  
Vol 53 (2) ◽  
pp. 522-527 ◽  
Author(s):  
Doron Boltin ◽  
Haim Ben-Zvi ◽  
Tsachi Tsadok Perets ◽  
Zvi Kamenetsky ◽  
Zmira Samra ◽  
...  

The current guidelines recommend culture and antibiotic susceptibility testing ofHelicobacter pylorifollowing two failed eradication attempts. Where testing is unavailable, epidemiological data for secondaryH. pyloriresistance are essential to allow for the rational use of antibiotics. The aim of this study was to describe the temporal changes in antibiotic resistance among adults previously treated forH. pyloriinfections and to identify predictors of resistance. Between 2007 and 2014, consecutive patients undergoing gastroscopy withH. pyloriculture and susceptibility testing at our institution following at least two treatment failures were retrospectively identified. Antibiotic susceptibilities were recorded and linked to the demographic data. A total of 1,042 patients were identified, including 739 (70.9%) males, aged 39.3 ± 18.9 years. Resistance to clarithromycin, metronidazole, and levofloxacin was found in 57.2%, 64.4%, and 5.1% of isolates, respectively. Dual resistance to clarithromycin and metronidazole was seen in 39.9%. Over the study period, clarithromycin resistance increased annually in a linear manner (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03 to 1.14;P< 0.01), levofloxacin resistance decreased annually (OR, 0.78; 95% CI, 0.61 to 0.92;P< 0.01), and metronidazole resistance was nonlinear. Age was an independent predictor of resistance to all antibiotics. Time elapsed predicted resistance for clarithromycin and levofloxacin and dual resistance for clarithromycin-metronidazole. Secondary resistance ofH. pylorito clarithromycin and metronidazole remains high. The low secondary resistance to levofloxacin makes it an attractive treatment option in our region for patients following two failed eradication attempts.

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1058
Author(s):  
Luis Bujanda ◽  
Olga P. Nyssen ◽  
Dino Vaira ◽  
Ilaria M. Saracino ◽  
Giulia Fiorini ◽  
...  

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.


2020 ◽  
Vol 75 (11) ◽  
pp. 3391-3394
Author(s):  
Tao Lyu ◽  
Ka Shing Cheung ◽  
Li Ni ◽  
Jiaqi Guo ◽  
Pei Mu ◽  
...  

Abstract Background We aimed to study the prevalence of secondary antibiotic resistance of Helicobacter pylori in southern China and its risk factors, particularly geographical and socio-economic factors. Methods This was a municipality-wide, multicentre, prospective cohort study involving five major hospitals. Patients aged ≥18 years who failed first-line bismuth-based quadruple anti-H. pylori therapy between September 2016 and February 2018 were recruited. Participants underwent upper gastrointestinal endoscopy with biopsy from the antrum and body for H. pylori culture and antimicrobial susceptibility testing for six antibiotics (clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline and furazolidone). Patients with failure of H. pylori culture were excluded. Participants completed a questionnaire profiling 22 potential risk factors of H. pylori infection and antibiotic resistance, including medical, social, household and birthplace factors. Results A total of 1113 patients failed first-line therapy, with successful H. pylori culture in 791 (71.1%) [male = 433 (54.7%); median age = 43 years]. Secondary resistance rates of dual antibiotics (clarithromycin + metronidazole and levofloxacin + metronidazole) and triple antibiotics (clarithromycin + levofloxacin + metronidazole) were 34.0%, 38.7% and 17.8%, respectively. Risk factors for clarithromycin + metronidazole resistance were history of ≥2 courses of H. pylori therapies [adjusted OR (aOR) = 1.71; 95% CI = 1.17–2.54], ≥3 household members (aOR = 2.00; 95% CI = 1.07–3.90) and family history of gastric cancer (aOR = 1.85; 95% CI = 1.18–2.85). Risk factors for levofloxacin + metronidazole resistance were age ≥40 years (aOR = 1.94; 95% CI = 1.37–2.75), lower gross domestic product per capita (aOR = 0.29; 95% CI = 0.10–0.80) and higher number of doctors/10 000 population (aOR = 1.59; 95% CI = 1.07–2.39). A higher human development index was of borderline significance (aOR = 2.79; 95% CI = 0.97–8.70). Conclusions The rates of secondary resistance of H. pylori to multiple antibiotics were high in southern China. Certain population-level risk factors were associated with levofloxacin + metronidazole resistance.


2021 ◽  
Author(s):  
Jinnan Chen ◽  
Yu Huang ◽  
Zhaohui Ding ◽  
Xiao Liang ◽  
Hong Lu

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Li ◽  
Jianjun Deng ◽  
Zhiling Wang ◽  
Hong Li ◽  
Chaomin Wan

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.


2000 ◽  
Vol 14 (10) ◽  
pp. 879-882 ◽  
Author(s):  
Carlo A Fallone

BACKGROUND: The rate ofHelicobacter pyloriresistance to antibiotics determines the cure rate of treatment regimens containing such antibiotics. AIMS: To review the literature to determine the rates ofH pyloriresistance to metronidazole and clarithromycin in Canada, and whether these rates vary in different regions of Canada.METHODS: The literature was reviewed extensively for the prevalence of antibiotic-resistantH pyloriin Canada by searching MEDLINE from January 1980 to May 1999, as well as abstracts of the American Gastroenterology Association Digestive Disease Week, Canadian Digestive Disease Week and The EuropeanH pyloriStudy Group Meetings from January 1995 to May 1999.RESULTS: Eleven studies that estimatedH pyloriresistance to metronidazole resistance and nine that estimated resistance to clarithromycin in Canada were identified. Rates of resistance for metronidazole and clarithromycin varied from 11% to 48% and 0% to 12%, respectively. Studies that obtained their estimates using the E-test and those that did not clearly exclude patients who had undergone previous attempts atH pylorieradication had higher estimates of resistance, accounting for this variability in results.CONCLUSIONS: The prevalence of primaryH pyloriresistance in Canada appears to be 18% to 22% for metronidazole and less than 4% for clarithromycin. These rates appear to be consistent across the different regions studied in Canada, but many regions have not been studied.


2020 ◽  
Vol 13 ◽  
pp. 175628482097699
Author(s):  
Chih-Ming Liang ◽  
Wei-Chen Tai ◽  
Pin-I Hsu ◽  
Deng-Chyang Wu ◽  
Chao-Hung Kuo ◽  
...  

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.


1998 ◽  
Vol 12 (4) ◽  
pp. 295-298 ◽  
Author(s):  
Diane E Taylor ◽  
Qin Jiang ◽  
Richard N Fedorak

The incidence of antibiotic resistance to amoxicillin, clarithromycin, erythromycin, metronidazole and tetracycline inHelicobacter pyloristrains isolated from gastric biopsy specimens obtained in Alberta was investigated. Results for all antibiotics were obtained using agar dilution, and in addition to metronidazole, the E test was used. Resistance to amoxicillin and tetracycline was not detected. Metronidazole resistance determined using agar dilution was approximately 12% (95% CI 4% to 26%) when minimal inhibitory concentrations (MICs) were at least 8 µg/mL, but fell to 2% (95% CI 0.1% to 13%) when MICs were set at 32 µg/mL or greater. The E test for metronidazole resistance (MIC 8 µg/mL or greater) yielded a slightly higher percentage of resistant strains compared with agar dilution tests (14%, 95% CI 5% to 29%). One of the 31 strains was resistant to clarithromycin (MIC 8 µg/mL) and erythromycin (MIC 16 µg/mL). Thus, the incidence of resistance to clarithromycin, part of the currently used triple therapy for eradication ofH pylori, was 3% (95% CI 0.1% to 17%).


2014 ◽  
Vol 63 (5) ◽  
pp. 703-709 ◽  
Author(s):  
Hanafiah Alfizah ◽  
Ahmad Norazah ◽  
Razlan Hamizah ◽  
Mohamed Ramelah

Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of H. pylori in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one H. pylori isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of H. pylori isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2  and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in rdxA and frxA genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gyrA gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in rdxA or frxA genes and point mutations in the 23S rRNA affected the efficacy of H. pylori eradication therapy.


2015 ◽  
Vol 59 (4) ◽  
pp. 2343-2348 ◽  
Author(s):  
Tran Thanh Binh ◽  
Rumiko Suzuki ◽  
Tran Thi Huyen Trang ◽  
Dong Hyeon Kwon ◽  
Yoshio Yamaoka

ABSTRACTMetronidazole resistance is a key factor associated withHelicobacter pyloritreatment failure. Although this resistance is mainly associated with mutations in therdxAandfrxAgenes, the question of whether metronidazole resistance is caused by the inactivation offrxAalone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptibleH. pyloristrain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistantH. pyloristrains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations infrxA(hp0642),rdxA(hp0954), andrpsU(hp0562) were confirmed by the Sanger method. The mutated sequence inrdxAwas successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation inrdxAshowed a low MIC (16 mg/liter), while those containing mutations in bothrdxAandfrxAshowed a higher MIC (48 mg/liter). No transformants containing a single mutation infrxAorrpsUwere obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations inrdxAare mainly associated with metronidazole resistance, and mutations infrxAare able to enhanceH. pyloriresistance only in the presence ofrdxAmutations. Moreover, mutations inrpsUmay play a role in metronidazole resistance.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Feng-Woei Tsay ◽  
Deng-Chyang Wu ◽  
Hsien-Chung Yu ◽  
Sung-Shuo Kao ◽  
Kung-Hung Lin ◽  
...  

ABSTRACT Hybrid therapy is a novel two-step treatment achieving a high eradication rate for Helicobacter pylori infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of H. pylori infection. From July 2013 to June 2015, eligible H. pylori-infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). H. pylori status was examined 6 weeks after the end of treatment. Three hundred thirty H. pylori-infected participants were randomized to receive 14-day bismuth quadruple therapy (n = 164) or 14-day hybrid therapy (n = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], −4.3% to 5.4%; P = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; P = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; P < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; P = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with H. pylori infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.)


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