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Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?

The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfer...

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Autores principales: Ierardi, Enzo, Giorgio, Floriana, Iannone, Andrea, Losurdo, Giuseppe, Principi, Mariabeatrice, Barone, Michele, Pisani, Antonio, Di Leo, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394508/
https://www.ncbi.nlm.nih.gov/pubmed/28465629
http://dx.doi.org/10.3748/wjg.v23.i14.2453
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author Ierardi, Enzo
Giorgio, Floriana
Iannone, Andrea
Losurdo, Giuseppe
Principi, Mariabeatrice
Barone, Michele
Pisani, Antonio
Di Leo, Alfredo
author_facet Ierardi, Enzo
Giorgio, Floriana
Iannone, Andrea
Losurdo, Giuseppe
Principi, Mariabeatrice
Barone, Michele
Pisani, Antonio
Di Leo, Alfredo
author_sort Ierardi, Enzo
collection PubMed
description The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.
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spelling pubmed-53945082017-05-02 Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy? Ierardi, Enzo Giorgio, Floriana Iannone, Andrea Losurdo, Giuseppe Principi, Mariabeatrice Barone, Michele Pisani, Antonio Di Leo, Alfredo World J Gastroenterol Editorial The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided. Baishideng Publishing Group Inc 2017-04-14 2017-04-14 /pmc/articles/PMC5394508/ /pubmed/28465629 http://dx.doi.org/10.3748/wjg.v23.i14.2453 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ 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.
spellingShingle Editorial
Ierardi, Enzo
Giorgio, Floriana
Iannone, Andrea
Losurdo, Giuseppe
Principi, Mariabeatrice
Barone, Michele
Pisani, Antonio
Di Leo, Alfredo
Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?
title Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?
title_full Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?
title_fullStr Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?
title_full_unstemmed Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?
title_short Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?
title_sort noninvasive molecular analysis of helicobacter pylori: is it time for tailored first-line therapy?
topic Editorial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394508/
https://www.ncbi.nlm.nih.gov/pubmed/28465629
http://dx.doi.org/10.3748/wjg.v23.i14.2453
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