Impact of Helicobacter pylori resistance in unsuccessfully pluritreated patients in a Department of Infectious Diseases in Rome

Twenty-five pluritreated patients were examined. Fifty-six percent yielded Helicobacter pylori (H. Pilory); of these, 9 patients showed a concomitant colonization of the three gastric regions. The highest resistance rate was found for metronidazole (71.8%) followed by chlaritromycin (53.1%). Amoxycillin showed the best susceptibility (only 6% of resistance), tetracycline showed 12% of resistant strains and levofloxacin appeared to be a promising antibacterial agent (18% of resistance). The E-test method was shown to be more suitable than disk diffusion technique for resistance testing. Combined resistance to both chlaritromycin and metronidazole appeared in 50% of the strains. The isolates showing this dual resistance are known to be difficult to eradicate. Resistotypes were shown to be genotypically different even if the strains with the resistance to both chlaritromycin and metronidazole are more likely to belong to genotype cagA+ and vacA s1m1. Heteroresistance (different susceptibility of the isolated strains in a single stomach) resulted in 36% of patients with pangastritis. Indeed, the concomitant presence of H. pylori strains in the same subject, either susceptible or resistant or vice versa, may interfere with the eradication outcomes. In our study, antibiotic resistant H. pylori typically develops from pre-existing susceptible strains rather than from co-infection with a different and unrelated strain. In fact, each pair of isolates detected in our 4 patients with heteroresistance belonged to the same genotype (cagA+ s1m2 in patient 1 and cagA+ s1m1 in patients 2, 3 and 4). In conclusion, H. pylori antibiotic resistance does present several issues in pluritreated patients owing to the rapid emergence of multi-resistant strains.

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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.

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

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820976990 ◽

2020 ◽

Vol 13 ◽

pp. 175628482097699

Author(s):

Chih-Ming Liang ◽

Wei-Chen Tai ◽

Pin-I Hsu ◽

Deng-Chyang Wu ◽

Chao-Hung Kuo ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Linear Trend ◽

Eradication Therapy ◽

Resistance Rate ◽

Test Method ◽

Success Rates ◽

Primary Resistance ◽

Secondary Resistance ◽

H Pylori

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.

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Variability in Prevalence ofHelicobacter pyloriStrains Resistant to Clarithromycin and Levofloxacin in Southern Poland

Gastroenterology Research and Practice ◽

10.1155/2012/418010 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Elżbieta Karczewska ◽

Karolina Klesiewicz ◽

Iwona Skiba ◽

Izabela Wojtas-Bonior ◽

Edward Sito ◽

...

Keyword(s):

Helicobacter Pylori ◽

Statistical Analysis ◽

Antimicrobial Agents ◽

Test Method ◽

Secondary Resistance ◽

Significance Level ◽

Southern Poland ◽

Resistant Strains ◽

Therapeutic Problem ◽

H Pylori

Background. An increasing resistance ofHelicobacter pyloristrains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance ofH. pyloristrains isolated between 2006–2008 (data published) and 2009–2011 to clarithromycin and levofloxacin.Material and Methods. 220 dyspeptic patients (153 before treatment, 67 after), were enrolled in the study. 51H. pyloristrains were isolated. MIC values of clarithromycin and levofloxacin were determined by theE-test method. The statistical analysis was conducted with theχ2test with Yates correction at the 0.05 significance level (P≤0.05).Results. Between 2006 and 2008, 34% (39/115) ofH. pyloristrains were resistant to clarithromycin (primary 21% (19/90), secondary 80% (20/25)). 5% (6/115) of strains were resistant to levofloxacin (primary 2% (2/90), secondary 16% ((4/25); data published) Between 2009–2011, 22% (11/51) ofH. pyloristrains were resistant to clarithromycin (primary 19% (8/43), secondary 38% (3/8)). 16% (8/51) of strains were resistant to levofloxacin (primary 12% (5/43), secondary 38% (3/8)).Conclusion. The present study has shown the increasing amount of resistantH. pyloristrains isolated from patients in Southern Poland to levofloxacin and decreasing number of resistant strains to clarithromycin.

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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.

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Appearance of a metronidazole-resistant Helicobacter pylori strain in an infected-ICR-mouse model and difference in eradication of metronidazole-resistant and -sensitive strains.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.12.2602 ◽

1997 ◽

Vol 41 (12) ◽

pp. 2602-2605 ◽

Cited By ~ 15

Author(s):

S Matsumoto ◽

Y Washizuka ◽

Y Matsumoto ◽

S Tawara ◽

F Ikeda ◽

...

Keyword(s):

Helicobacter Pylori ◽

Mouse Model ◽

Resistant Strain ◽

Sensitive Strain ◽

Original Strain ◽

Antibiotic Resistant ◽

Icr Mouse ◽

Resistant Strains ◽

H Pylori

We tested whether antibiotic-resistant strains appeared in vivo after the failure of treatment using the Helicobacter pylori-infected euthymic mouse model. The numbers of colonies isolated from 56 ICR mice 2 weeks after 4 days of treatment with metronidazole (3.2, 10, or 32 mg/kg of body weight) or amoxicillin (1, 3.2 or 10 mg/kg), with treatment started 4 days after H. pylori CPY2052 inoculation, were counted, and the isolated strains were tested for their sensitivities to two antibiotics to rule out the presence of antibiotic-resistant strains. One metronidazole-resistant strain was detected in a mouse treated with 10 mg of metronidazole per kg, and the MIC of metronidazole for this strain was 25 microg/ml, compared to a MIC of 1.56 microg/ml for the original strain. However, no resistant strain was detected in the amoxicillin treatment group. After the examination described above, mice challenged with a metronidazole-resistant or -sensitive strain isolated from the stomach of a mouse were treated with metronidazole or amoxicillin. The metronidazole-resistant strain was more difficult to eradicate in vivo than the sensitive strain after treatment with metronidazole but not after treatment with amoxicillin. Thus, a metronidazole-resistant H. pylori strain was selected by insufficient treatment, but no resistant strain was selected with amoxicillin. Eradication of a metronidazole-resistant H. pylori strain in vivo required a higher dosage than eradication of a metronidazole-sensitive H. pylori strain. These results may explain one of the reasons for H. pylori treatment failure.

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Synergism of the Combination of Traditional Antibiotics and Novel Phenolic Compounds against Escherichia coli

Pathogens ◽

10.3390/pathogens9100811 ◽

2020 ◽

Vol 9 (10) ◽

pp. 811

Author(s):

Md. Akil Hossain ◽

Hae-Chul Park ◽

Sung-Won Park ◽

Seung-Chun Park ◽

Min-Goo Seo ◽

...

Keyword(s):

Escherichia Coli ◽

Rattus Norvegicus ◽

Inhibitory Concentration ◽

Epicatechin Gallate ◽

Antibiotic Resistant ◽

E Coli ◽

Pathogenic Escherichia Coli ◽

Resistant Strains ◽

Novel Approaches ◽

Rapid Emergence

Pathogenic Escherichia coli (E. coli)-associated infections are becoming difficult to treat because of the rapid emergence of antibiotic-resistant strains. Novel approaches are required to prevent the progression of resistance and to extend the lifespan of existing antibiotics. This study was designed to improve the effectiveness of traditional antibiotics against E. coli using a combination of the gallic acid (GA), hamamelitannin, epicatechin gallate, epigallocatechin, and epicatechin. The fractional inhibitory concentration index (FICI) of each of the phenolic compound-antibiotic combinations against E. coli was ascertained. Considering the clinical significance and FICI, two combinations (hamamelitannin-erythromycin and GA-ampicillin) were evaluated for their impact on certain virulence factors of E. coli. Finally, the effects of hamamelitannin and GA on Rattus norvegicus (IEC-6) cell viability were investigated. The FICIs of the antibacterial combinations against E. coli were 0.281–1.008. The GA-ampicillin and hamamelitannin-erythromycin combinations more effectively prohibited the growth, biofilm viability, and swim and swarm motilities of E. coli than individual antibiotics. The concentration of hamamelitannin and GA required to reduce viability by 50% (IC50) in IEC-6 cells was 988.54 μM and 564.55 μM, correspondingly. GA-ampicillin and hamamelitannin-erythromycin may be potent combinations and promising candidates for eradicating pathogenic E. coli in humans and animals.

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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.

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Efficacy of and Resistance to Rifaximin-based Quadruple Therapy in Helicobacter pylori Eradication

The Korean Journal of Helicobacter and Upper Gastrointestinal Research ◽

10.7704/kjhugr.2020.0021 ◽

2020 ◽

Vol 20 (3) ◽

pp. 218-224

Author(s):

Hyun Soo Kim ◽

Hyuk Yoon ◽

Dong Woo Shin ◽

Dong Jun Oh ◽

Mingu Kwon ◽

...

Keyword(s):

Helicobacter Pylori ◽

Rescue Therapy ◽

Treatment Options ◽

Treatment Protocol ◽

Resistance Rate ◽

Quadruple Therapy ◽

Minimal Inhibitory Concentrations ◽

Intention To Treat ◽

H Pylori ◽

Triple Regimen

Background/Aims: The treatment options for Helicobacter pylori (H. pylori) infection are in a state of flux: traditional triple therapies have started to fail, and new treatments are unable to achieve optimal eradication rates. Rifaximin and rifabutin are new antibiotics. The aim of this study was to evaluate the efficacy and safety of adding rifaximin to the standard triple regimen and of a rifabutin-based triple regimen as a rescue therapy for H. pylori eradication.Materials and Methods: We enrolled 27 H. pylori-positive patients who were treated with a proton pump inhibitor, amoxicillin, clarithromycin, and rifaximin for 14 days. H. pylori eradication was assessed by a 13C-urea breath test performed 4 weeks after therapy completion. The efficacy of the therapy was based on intention-to-treat (ITT) and per-protocol (PP) analysis. We also investigated the resistance rate, compliance, and side effects associated with rifaximin therapy. Minimal inhibitory concentrations and resistance to rifabutin were evaluated using the agar dilution method.Results: Of the 27 patients, 22 completed the treatment protocol with 100% compliance; five patients withdrew. The ITT and PP eradication rates for the rifaximin-containing quadruple therapy were 70.4% (19/27) and 86.3% (19/22), respectively. Adverse events were observed in five of 22 patients (22.7%). The resistance rates to rifaximin and rifabutin were 66.7% (2/3) and 0% (0/3), respectively.Conclusions: The findings of this study show the limitations of rifaximin-based quadruple therapy and suggest the benefits of a rifabutin-based rescue regimen in South Korea.

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Antibiotic Resistance and Genotypes of Helicobacter pylori Strains in Patients with Gastroduodenal Disease in Southeast Poland

Journal of Clinical Medicine ◽

10.3390/jcm8071071 ◽

2019 ◽

Vol 8 (7) ◽

pp. 1071 ◽

Cited By ~ 3

Author(s):

Izabela Korona-Glowniak ◽

Halina Cichoz-Lach ◽

Radoslaw Siwiec ◽

Sylwia Andrzejczuk ◽

Andrzej Glowniak ◽

...

Keyword(s):

Genetic Diversity ◽

Helicobacter Pylori ◽

Test Method ◽

Rapid Urease Test ◽

Microbial Culture ◽

Virulence Markers ◽

Gastroduodenal Disease ◽

Urease Test ◽

Gastric Biopsies ◽

H Pylori

The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested for presence of H. pylori with the use of rapid urease test, microbial culture, and polymerase chain reaction (PCR) detection. The genetic diversity of 62 H. pylori positive samples was evaluated by detection of cagA and PCR-typing of vacA and iceA virulence-associated genes. Most common H. pylori genotypes were cagA(+)vacAs1m2 (27.4%) and cagA(−)vacAs2m2 (24.2%). In logistic regression analysis, we recognized the subsequent significant associations: gastritis with ureC, i.e., H. pylori infection (p = 0.006), BMI index (p = 0.032); and negatively with iceA1 (p = 0.049) and peptic ulcer with cagA (p = 0.018). Thirty-five H. pylori strains were cultured and tested by E-test method showing that 49% of strains were resistant to at least one of the tested antibiotics. This is the first study that reports the high incidence and diversity of allelic combination of virulence genes in gastroduodenitis patients in Poland. Genotyping of H. pylori strains confirmed the involvement of cagA gene and vacAs1m1 genotype in development and severity of gastric disorder.

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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.

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