The life and death of Helicobacter pylori

Scott, David; Weeks, David L.; Melchers, Klaus; Sachs, George

doi:10.1136/gut.43.2008.s56

Cited by 192 publications

(190 citation statements)

References 14 publications

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“…Treatment for eradication of H. pylori includes PPIs along with antimicrobial agents [68,69]. The role of PPIs is to increase the intragastric pH, allowing the bacteria to reach the growth phase and become more sensitive to antibiotics [69].…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

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Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

190

172

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Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

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Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…The role of PPIs is to increase the intragastric pH, allowing the bacteria to reach the growth phase and become more sensitive to antibiotics [69]. Additionally, the increased pH increases the stability of antibiotics, allowing for increased antimicrobial activity [68].…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

190

172

View full text Add to dashboard Cite

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“…This concept is not new as it was first described by Bigger in 1944 49 . In H. pylori infections, it has been suggested that pH lower than 6 in the microenvironment surrounding the bacteria is responsible for maintaining the bacteria in a nonreplicative state as H. pylori do not replicate at pH's below 6 such that increasing the local pH may restore replication 50 . This concept has been the theoretical basis for the successful revival of PPI plus amoxicillin dual therapy 51 (see below).…”

Section: Why Are H Pylori Difficult To Eradicate?mentioning

confidence: 99%

New concepts of resistance in the treatment of Helicobacter pylori infections

Graham

Shiotani

2008

Nat Rev Gastroenterol Hepatol

316

368

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SummaryThe prevalence of antimicrobial resistance is now such that all patients should be considered as having resistant infections. Ideally therapy is based on pretreatment susceptibility testing. Empiric therapies should assume antimicrobial resistance and use higher doses for 14 days. Acceptable results are 90-94% cure intention to treat (Grade B) or greater. Clarithromycin-containing triple therapies now typically produce ≤80% cure ITT (Grade F) and are no longer acceptable empiric therapy. Current initial therapy options are between sequential therapy, concomitant therapy, and bismuth containing quadruple therapy. Sequential therapy has the potential to be improved to ≥95% cure ITT (Grade A) by continuing the amoxicillin through the second and/or by increasing the duration. Better appreciation of the role of acidity in phenotypic resistance has resulted in high cure rates with high dose PPI plus amoxicillin dual therapy; additional studies to devise better dual-based multidrug regimes are still needed. Antimicrobial choices following treatment failure is best approached by susceptibility testing. If not available, we recommended a bismuth containing quadruple therapy substituting a new drug for metronidazole/tinidazole and/or clarithromycin if they have been used previously. The alternate would be to use a 14 day high dose PPI, amoxicillin-based triple therapy with rifabutin, a fluoroquinolone, or furazolidone. KeywordsHelicobacter pylori; therapy; resistance; antibiotics; anti-secretory drugs; phenotypic drug resistance; cytochrome P450 "To read without reflecting is like eating without digesting". -86-462-1111-86-462- , FAX 81-86-464-1195 Review criteria: We searched the relevant papers by using computer-assisted bibliographic searches of PubMed through November 30, 2007 using combinations of the following terms: H. pylori combined with resistance, therapy, eradication, second, triple, quadruple, sequential, or rescue. We also reviewed the recent literature on pharmacokinetics and pharmacodynamics in relation to the drugs used in H. pylori therapy and the relation to host cytochrome P450 genotypes to treatment outcome. We did not perform meta-analyses. We reviewed only articles published in English.

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“…Histologic studies in combination with culture confirmed that PPI use is associated with a change in the distribution of gastritis with histological improvement in antrum and worsening of the gastritis in the body portion of the stomach 44. These changes have been attributed to alteration in local pH as H. pylori are killed at pHs below 4 and above 8, are able to survive but not replicate at pHs between 4 and 6 and only replicate at pHs between 6 and 8 45. Kuipers et al .…”

Section: Discussionmentioning

confidence: 92%

Proton pump inhibitors and risk of periampullary cancers—A nested case–control study

Chien

Huang

Shao

et al. 2015

Intl Journal of Cancer

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Considerable attention has been focused on long‐term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA‐damaged cells. The aim of this study is to examine the dose‐dependent effect of PPI on periampullary cancers in a national population‐based cohort. A nested case–control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A “PPI user” was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow‐up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16–1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose‐dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long‐term PPI use was associated with an increased risk of periampullary cancers in the current population‐based study. Physicians must weigh potential risks of long‐term maintenance against therapeutic benefit.

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The life and death of Helicobacter pylori

Cited by 192 publications

References 14 publications

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

New concepts of resistance in the treatment of Helicobacter pylori infections

Proton pump inhibitors and risk of periampullary cancers—A nested case–control study

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