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World J Gastroenterol. Sep 14, 2019; 25(34): 5097-5104
Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5097
Optimizing proton pump inhibitors in Helicobacter pylori treatment: Old and new tricks to improve effectiveness
Enzo Ierardi, Giuseppe Losurdo, Rosa Federica La Fortezza, Mariabeatrice Principi, Michele Barone, Alfredo Di Leo
Enzo Ierardi, Giuseppe Losurdo, Rosa Federica La Fortezza, Mariabeatrice Principi, Michele Barone, Alfredo Di Leo, Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
Author contributions: Ierardi E, Losurdo G and Di Leo A planned the study; La Fortezza RF, Principi M and Barone M collected the data; Ierardi E, Losurdo G and La Fortezza RF wrote the first draft; all authors read and approved the final version; Ierardi E and Losurdo G contributed equally and are co-first authors.
Conflict-of-interest statement: None declared.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Enzo Ierardi, MD, Academic Fellow, Associate Professor, Doctor, Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11, Bari 70124, Italy. e.ierardi@virgilio.it
Telephone: +39-80-5593452 Fax: +39-80-5593088
Received: May 28, 2019
Peer-review started: May 28, 2019
First decision: July 21, 2019
Revised: July 26, 2019
Accepted: August 7, 2019
Article in press: August 7, 2019
Published online: September 14, 2019
Abstract

The survival and replication cycle of Helicobacter pylori (H. pylori) is strictly dependant on intragastric pH, since H. pylori enters replicative phase at an almost neutral pH (6-7), while at acid pH (3-6) it turns into its coccoid form, which is resistant to antibiotics. On these bases, it is crucial to increase intragastric pH by proton pump inhibitors (PPIs) when an antibiotic-based eradicating therapy needs to be administered. Therefore, several tricks need to be used to optimize eradication rate of different regimens. The administration of the highest dose as possible of PPI, by doubling or increasing the number of pills/day, has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies, even if specific trials have not been performed. A pre-treatment with PPI before starting antibiotics does not seem to be effective, therefore it is discouraged. However, the choice of PPI molecule could have a certain weight, since second-generation substances (esomeprazole, rabeprazole) are likely more effective than those of first generation (omeprazole, lansoprazole). A possible explanation is due to their metabolism, which has been proven to be less dependent on cytochrome P450 (CYP) 2C19 genetic variables. Finally, vonoprazan, a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy, due to both its highest acid inhibition power and rapid pharmacologic effect. However current data come only from Eastern Asia, therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.

Keywords: Helicobacter pylori, Proton pump inhibitors, Eradication, Cytochrome P450, Optimization

Core tip: The most adequate acid suppression by proton pump inhibitors (PPIs) is fundamental to optimize antibiotic therapies for Helicobacter pylori eradication. Herein, we summarize data from literature in order to ascertain the most effective strategies in this topic. Increasing PPI dose showed a real benefit on eradication rate even in the absence of dedicated trials. Second-generation PPIs, as demonstrated in some meta-analyses, may be more effective than old PPI molecules. Finally, vonoprazan, a novel molecule, has shown promising results but, currently, data come from Asian countries, therefore its strong power needs to be confirmed outside this geographic area.