Retrospective study on outcome of salvage <i>Helicobacter pylori</i> eradication therapies based on molecular genetic susceptibility testing

Blümel, Benjamin; Goelz, Hanna; Kist, Manfred; Glocker, Erik-Oliver

doi:10.1111/hel.12494

Cited by 12 publications

(22 citation statements)

References 28 publications

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“…Drug resistance among clinical isolates of H. pylori is a well-recognized issue, and susceptibility-guided treatment of H. pylori infection is crucial to attain a better treatment response among infected individuals (41). WHO has listed H. pylori as a highpriority pathogen for which there is an urgent need to develop new antimicrobials (42).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing

et al. 2020

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The emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While the alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding the molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole-genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa coefficient, 0.84; 95% confidence interval [CI], 0.67 to 1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa coefficient, 0.90; 95% CI, 0.77 to 1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa coefficient, 0.76; 95% CI, 0.56 to 0.96). Previously identified mutations in the rpoB rifampin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampin-resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates, and our findings support the use of WGS for the detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing

et al. 2020

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“…The limitations of this study are the lack of a reference method for clarithromycin resistance, the lack of samples of non-infected individuals to determine the specificity of the method for the detection of infection when using FFPE tissue, and the lack of information on previous eradication therapies. 34 In this context, two similar studies from Korea showed significantly higher eradication rates of tailored firstline therapies in comparison with the conventional empirical triple therapy consisting of clarithromycin, amoxicillin and a PPI. The latter showed the highest positivity rate, which was not affected by the use of PPI in contrast to the other methods.…”

Section: Molecular Methodsmentioning

confidence: 97%

“…Even though current guidelines recommend susceptibility testing to be performed only after two treatment failures, the authors conclude that it may be reasonable to perform susceptibility testing as early as possible, since tailored first-line treatments are superior to empiric ones and may also be cost-effective. 34 In this context, two similar studies from Korea showed significantly higher eradication rates of tailored firstline therapies in comparison with the conventional empirical triple therapy consisting of clarithromycin, amoxicillin and a PPI. In both studies, tailored treatment was guided by molecular detection of mutations associated with clarithromycin resistance in gastric biopsies; however, there was some controversy regarding the costeffectiveness of this approach which depends on local costs.…”

Section: Molecular Methodsmentioning

confidence: 97%

Review: Diagnosis of Helicobacter pylori infection

et al. 2019

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Endoscopic imaging of the stomach is improving. In addition to narrow band imaging, other methods, for example, blue light imaging and linked color imaging, are now available and can be combined with artificial intelligence systems to obtain information on the gastric mucosa and detect early gastric cancer. Immunohistochemistry is only recommended as an ancillary stain in case of chronic active gastritis without Helicobacter pylori detection by standard staining, and recommendations to exclude false negative H. pylori results have been made. Molecular methods using real‐time PCR, droplet digital PCR, or amplification refractory mutation system PCR have shown a high accuracy, both for detecting H. pylori and for clarithromycin susceptibility testing, and can now be used in clinical practice for targeted therapy. The most reliable non‐invasive test remains the 13C‐urea breath test. Large data sets show that DOB values are higher in women and that the cut‐off for positivity could be decreased to 2.74 DOB. Stool antigen tests using monoclonal antibodies are widely used and may be a good alternative to UBT, particularly in countries with a high prevalence of H. pylori infection. Attempts to improve serology by looking at specific immunodominant antigens to distinguish current and past infection have been made. The interest of Gastropanel® which also tests pepsinogen levels was confirmed.

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“…33 Cure, however, was only achieved in 68% of patients. A German study looked at real-time genotypic clarithromycin and/or levofloxacin susceptibility as tested by PCR analysis of 144 H pylori-positive strains from patients with prior treatment failure.…”

Section: Suscep Tib Ilit Y-g Uided Ther Apymentioning

confidence: 93%

“…A German study looked at real-time genotypic clarithromycin and/or levofloxacin susceptibility as tested by PCR analysis of 144 H pylori-positive strains from patients with prior treatment failure. 33 Cure, however, was only achieved in 68% of patients. More encouraging results were obtained in a large, multicenter open-label trial of 450 patients who had failed two previous treatment regimes where genotypic resistance tailored treatment led to 78% eradication, but in this case empirical quadruple sequential therapy with a cure rate of 71% was an acceptable alternative after consideration of accessibility, cost, and patient preference.…”

Section: Suscep Tib Ilit Y-g Uided Ther Apymentioning

confidence: 93%

Review: Treatment of Helicobacter pylori Infection 2019

et al. 2019

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This review summarizes important studies regarding Helicobacter pylori therapy published from May 2018 to May 2019. The main themes that emerge involve studies assessing the efficacy of bismuth‐based regimens. While in recent years the efficacy of bismuth‐based quadruple therapy as a second‐line therapy has been clearly established, there is now substantial evidence that it is the best performing first‐line therapy. Antibiotic resistance was again intensely studied this year, and a clear and dramatic increase in resistance is noted for clarithromycin and levofloxacin; most notably, it may not be possible to support these therapies in most regions of the world much longer without testing. The utility of vonoprazan as an alternative to proton‐pump inhibitor therapy, especially in resistant and difficult to treat groups, has also been considered in greater detail this year, as well as means of supporting and enhancing adherence to therapy. Several studies showed that the diversity of gut microbiota was significantly altered shortly after H pylori eradication. However, the diversity was restored to pre‐treatment state after 2 months in patients treated with triple therapy. More studies are warranted to assess the long‐term changes of gut microbiota after H pylori eradication.

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Retrospective study on outcome of salvage Helicobacter pylori eradication therapies based on molecular genetic susceptibility testing

Abstract: Eradication success was poor despite susceptibility testing. Gastroenterologists are advised to prescribe recommended salvage treatments, considering recommended dosages and prolonged treatment duration.

Cited by 12 publications

References 28 publications

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing

Review: Diagnosis of Helicobacter pylori infection

Review: Treatment of Helicobacter pylori Infection 2019

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