Role of bismuth in improving<i>Helicobacter pylori</i>eradication with triple therapy

Dore, Maria Pina; Lü, Hong; Graham, David Y.

doi:10.1136/gutjnl-2015-311019

Cited by 225 publications

(278 citation statements)

References 108 publications

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“…We showed that the Niu transporter is additionally involved in cobalt uptake, while the NixA permease is not, although the latter belongs to the NiCoT family. Bismuth, a metal that is not a natural protein cofactor, is a component of the new Pylera medication, in combination with two antibiotics and a proton pump inhibitor [64]. Pylera has proven to be more efficient in eradicating H .…”

Section: Discussionmentioning

confidence: 99%

Characterization in Helicobacter pylori of a Nickel Transporter Essential for Colonization That Was Acquired during Evolution by Gastric Helicobacter Species

et al. 2016

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Metal acquisition is crucial for all cells and for the virulence of many bacterial pathogens. In particular, nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori as it is the cofactor of two enzymes essential for in vivo colonization, urease and a [NiFe] hydrogenase. To import nickel despite its scarcity in the human body, H. pylori requires efficient uptake mechanisms that are only partially defined. Indeed, alternative ways of nickel entry were predicted to exist in addition to the well-described NixA permease. Using a genetic screen, we identified an ABC transporter, that we designated NiuBDE, as a novel H. pylori nickel transport system. Unmarked mutants carrying deletions of nixA, niuD and/or niuB, were constructed and used to measure (i) tolerance to toxic nickel exposure, (ii) intracellular nickel content by ICP-OES, (iii) transport of radioactive nickel and (iv) expression of a reporter gene controlled by nickel concentration. We demonstrated that NiuBDE and NixA function separately and are the sole nickel transporters in H. pylori. NiuBDE, but not NixA, also transports cobalt and bismuth, a metal currently used in H. pylori eradication therapy. Both NiuBDE and NixA participate in nickel-dependent urease activation at pH 5 and survival under acidic conditions mimicking those encountered in the stomach. However, only NiuBDE is able to carry out this activity at neutral pH and is essential for colonization of the mouse stomach. Phylogenomic analyses indicated that both nixA and niuBDE genes have been acquired via horizontal gene transfer by the last common ancestor of the gastric Helicobacter species. Our work highlights the importance of this evolutionary event for the emergence of Helicobacter gastric species that are adapted to the hostile environment of the stomach where the capacity of Helicobacter to import nickel and thereby activate urease needs to be optimized.

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Section: Discussionmentioning

confidence: 99%

Characterization in Helicobacter pylori of a Nickel Transporter Essential for Colonization That Was Acquired during Evolution by Gastric Helicobacter Species

et al. 2016

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“…The recommended eradication regimen in Northern Europe is triple therapy with a PPI in combination with clarithromycin and amoxicillin or metronidazole for 7 days [5]. A treatment alternative with comparable efficacy is bismuth-containing quadruple therapy, since the addition of bismuth can lead to a 30-40% increase in eradication success in areas with high antibiotic resistance [6]. However, bismuth is rarely used in Sweden, and many other combinations of antibiotics can also be prescribed [5].…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori eradication in the Swedish population

Doorakkers

Lagergren

Gajulapuri

et al. 2017

Scandinavian Journal of Gastroenterology

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Objectives: Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade. Materials and methods: This population-based study used data from the Swedish Prescribed Drug Register. From July 2005 until December 2014, all regimens that can eradicate H. pylori were identified and evaluated according to patients' age and sex and calendar year of eradication. Results: We identified 157,915 eradication episodes in 140,391 individuals (53.8% women, 42.6% older than 60 years), who correspond to 1.5% of the Swedish population. The absolute number and incidence of eradications decreased over the study period. Overall, 91.0% had one eradication and 0.1% had more than three. Of all eradications, 95.4% followed the recommended regimen, while 4.7% did not. The latter group was overrepresented among individuals aged 80 years (7.8%). Amoxicillin and clarithromycin were most frequently prescribed, while metronidazole was rarely used (0.01%). Other prescribed antibiotics were ciprofloxacin (2.4%), doxycycline (1.4%), nitrofurantoin (0.7%), norfloxacin (0.5%) and erythromycin (0.3%). Conclusions: During the last decade in Sweden H. pylori eradication has been frequently prescribed, but the incidence of eradication has slowly declined. Most eradications followed the recommended regimen, including those occurring after a previous eradication. ARTICLE HISTORY

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“…The treatment outcome in a population is based on the following formula: (% success with susceptible strains) + (% success with resistant strains) = overall eradication rate (Dore et al, 2016). The eradication rates of different regimens (14-day triple therapies, sequential therapies, concomitant therapies, BQTs, levofloxacin triple therapies or 7-day vonoprazan triple therapies) are greater than 95% in subpopulations with susceptible infections.…”

Section: Treatmentmentioning

confidence: 99%

Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

Zhu

Lü

2017

Front. Cell. Infect. Microbiol.

134

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Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

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Role of bismuth in improvingHelicobacter pylorieradication with triple therapy

Cited by 225 publications

References 108 publications

Characterization in Helicobacter pylori of a Nickel Transporter Essential for Colonization That Was Acquired during Evolution by Gastric Helicobacter Species

Characterization in Helicobacter pylori of a Nickel Transporter Essential for Colonization That Was Acquired during Evolution by Gastric Helicobacter Species

Helicobacter pylori eradication in the Swedish population

Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

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