Clinical Implication of Drug Resistance for H. pylori Management.

Rates of antimicrobial-resistance among H. pylori strains are increasing worldwide, resulting in declining eradication rates with current therapies, especially those containing clarithromycin or levofloxacin. To improve H. pylori management, a paradigm shift is needed, from the empiric approaches formerly employed, to regimen selection based upon knowledge of local and patient-level antimicrobial susceptibility data. We review the mechanisms of H. pylori antimicrobial resistance and the available worldwide pattern of resistance to key antimicrobials used in H. pylori therapy. The practicalities and challenges of measuring susceptibility in clinical practice is discussed, including not only conventional culture-based techniques but also novel sequencing-based methods performed on gastric tissue and stool samples. Though clinical trials of "tailored" (susceptibility-based) treatments have yet to show the clear superiority of tailored over empiric regimen selection, the ability to measure and modify treatment based upon antimicrobial susceptibility testing is likely to become more frequent in clinical practice and should lead to improved H. pylori management in the near future.

Helicobacter pylori Treatment Regimens: A US Perspective.

Helicobacter pylori infects nearly one-third of the US population. H pylori is a significant cause of gastroduodenal disease, including peptic ulcers and cancers. However, rising antibiotic resistance has complicated management of H pylori. This article provides a practical review of management strategies, including first-line empiric therapies and how to treat patients when prior therapies fail. Bismuthbased quadruple therapy remains the standard initial empiric regimen, although a rifabutin-based triple regimen is another approach for empiric therapy in the United States. Clarithromycin and levofloxacin therapies should be avoided except when treating a strain of known susceptibility. When therapies fail, resistance should be tested with molecular or culture-based methods. Knowing local resistance patterns and/or using practice-based eradication rates is important for devising logic-based clinical choices. Ultimately, shared decision-making, patient counseling, and careful attention to drug type and dosage are essential for refractory cases.

The prevention of gastric cancer by Helicobacter pylori eradication.

PURPOSE OF REVIEW: Gastric cancer remains one of the most common causes of death globally. Increasing evidence suggests that many gastric cancer cases can be prevented by eradicating its most important etiological agent, Helicobacter pylori. Using the search terms 'H. pylori' and 'gastric cancer' we reviewed the scientific literature regarding the association between H. pylori and gastric cancer published from 1 January 2020 to 30 May 2021. We review the most important articles relevant to the clinical issues regarding H. pylori eradication for gastric cancer prevention. RECENT FINDINGS: In randomized trials, eradication of H. pylori is associated with an approximately 50% reduction in sporadic gastric cancer. A similar benefit was observed when screening first-degree relatives of gastric cancer cases, after resection of early gastric cancer to prevent metachronous neoplasia, and in population-based screen and treatment programs in areas of high H. pylori and gastric cancer prevalence. Even in relatively low gastric cancer countries such as the United States, gastric cancer may potentially be avoided by screening for H. pylori, especially among minority groups who are at greatest risk. SUMMARY: Gastric cancer is preventable, at least in part, by H. pylori eradication. Ongoing screening trials will help determine whether population-based H. pylori screening programs are feasible and cost-effective. Their results are likely to differ according to H. pylori and gastric cancer prevalence rates.

Management of Helicobacter pylori.

PURPOSE OF REVIEW: Gastroenterologists and many general internists and primary care physicians confront questions regarding the management of Helicobacter pylori on a daily basis. The subject remains of global interest and continue to generate debate and research. Using the search terms 'pylori and treatment' or 'pylori and management' we identified over 1000 relevant articles in PubMed published over the time period 1 January 2019 to 30 April 2020. We have selected the most highly clinically relevant of these to review here. RECENT FINDINGS: Clinical evidence grows regarding the benefits of H. pylori eradication on gastric cancer prevention. High rates of resistance to clarithromycin and levofloxacin, correlating with treatment failure in regimens utilizing these drugs, has stimulated interest in alternative regimens as well as the need for susceptibility testing of individual patients and populations. Although many aspects of H. pylori management are well established, implementation of appropriate testing and treatment pathways remains suboptimal throughout healthcare settings. SUMMARY: Increased emphasis on measuring H. pylori-related clinical outcomes in practice is needed to identify implementation gaps, and to suggest means to best apply the knowledge gained on H. pylori for the prevention of gastric symptoms and disease.

Treatment of Helicobacter pylori.

PURPOSE OF REVIEW: Helicobacter pylori eradication has become more challenging over the past decade due to increasing antimicrobial resistance, especially to clarithromycin and levofloxacin. We identified 508 recent publications on H. pylori treatment (published between January 2018 and June 2019), focusing on the most highly clinically relevant for this review. RECENT FINDINGS: Declining H. pylori eradication rates with clarithromycin triple therapy have led to most guidelines recommending 14 days bismuth-based quadruple therapy or concomitant therapy as the best initial empiric regimen. Substituting amoxicillin for tetracycline or metronidazole in quadruple therapy, and a three-in-one pill version of the regimen, also appear effective. Vonoprazan, a potent acid inhibitor, can overcome much clarithromycin resistance in triple therapy. High-dose dual therapy (proton pump inhibitor with amoxicillin) is a promising alternative approach. Reviewing resistance patterns to select suitable first-line empiric therapies is important in high resistance regions. Molecular methods to evaluate H. pylori antimicrobial susceptibility promise to be simpler than standard microbiological culture. The cost-effectiveness of antimicrobial susceptibility testing in refractory cases remains unproven. SUMMARY: Updating clinicians treating H. pylori is important to combat the emerging problems of multidrug antimicrobial resistance in H. pylori strains. Truly novel approaches to H. pylori eradication are needed.

A Case of Acute Esophageal Necrosis.

Acute esophageal necrosis (AEN) is a rare condition that impacts the distal esophagus after a vascular insult. In this case report, we describe a patient with multiple comorbid conditions presenting with shock from gastroenteritis who subsequently developed AEN complicated by refractory strictures.

Unusual non-enzymatic flavin catalysis enhances understanding of flavoenzymes.

Flavin cofactors are central to many biochemical transformations and are typically tightly bound as part of a catalytically active flavoenzyme. This work indicates that naturally occurring flavins can act as stand-alone catalysts to promote the oxidation of biosynthetically inspired heterocycles in aqueous buffers. Flavin activity was compared with that of oxidases important in non-ribosomal peptide synthesis, providing a rare direct comparison between the catalytic efficacy of flavins alone and in the context of a full flavoenzyme. This study suggests that such oxidases are likely to possess an active site base, as oxidase activity was greater than that of flavins alone, particularly for less acidic substrates. These findings offer perspective on the development of robust and catalytically effective, designed miniature flavoenzymes.