High Levels of Helicobacter pylori Antimicrobial Resistance in Ireland—A Multicentre Study
, Stephen Molloy 1, Atiyekeogbebe Douglas 1, Denise Brennan 1, Rebecca FitzGerald 1, Conor Costigan 1,2, Vikrant Parihar 3, Kevin Van Der Merwe 3, Serhiy Semenov 4, Donal Tighe 4, Sharon Hough 5, David Kevans 1,5, Colm O’Morain 1, Deirdre McNamara 1,2,†and Sinéad Marian Smith 1,*,†Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis study aims to assess H. pylori antimicrobial resistance rates in Ireland and to identify patient risk factors associated with resistant strains. The author addresses a significant yet underexplored issue in national research. The introduction provides a thorough and clear overview of the topic and existing scientific knowledge. Methods and findings are explained transparently, and the authors compare their current observations with earlier studies in a well-organized, comprehensible way.
I recommend a slight adjustment to the methodology, as the primary and secondary antibiotic resistance terms should be clearly defined in line with what is being studied in this study.
Comments for author File: 
Comments.pdf
Author Response
Thank you for this important suggestion - we have added the definition of primary and secondary resistance to Methods Section 2.5.
Reviewer 2 Report
Comments and Suggestions for AuthorsIn the paper titled "High levels of Helicobacter pylori antimicrobial resistance in Ireland – a multicenter study," the authors present the results of a study on the drug resistance of H. pylori strains isolated from patients in Ireland and identify risk factors associated with harboring antimicrobial-resistant strains. The study utilized a combined corpus and antrum biopsy sampling approach to culture H. pylori and investigated resistance to all six antimicrobials in clinical use for H. pylori. This is an interesting study, and my minor comments are as follows:
- The methodological section requires further clarification ("Using a sterile inoculating loop, the corpus and antrum biopsies from each patient were spread onto a Columbia blood agar..."). Please specify whether the biopsy was subjected to any processing (e.g., homogenization) before inoculation.
- The Authors demonstrated that resistance to clarithromycin, amoxicillin, and dual resistance to clarithromycin and amoxicillin (or metronidazole) were more frequently observed in strains isolated from women than men, explaining this by the more frequent treatment undertaken in this group. However, the reader will be interested in a more in-depth analysis of this phenomenon. In other words, what else, besides more frequent treatment, could explain these observations? Could it be related to lower eradication rates, metabolic factors, physiology, immune response, bacterial load, or simply to random sample selection? Is there evidence of such gender-specific observations in the literature? Without this analysis, it is difficult to agree with the statement that "female sex was associated with an increased risk of resistance."
- Table 6 should be placed in the "Results" section, not in the Discussion.
Author Response
Reviewer 2
In the paper titled "High levels of Helicobacter pylori antimicrobial resistance in Ireland – a multicenter study," the authors present the results of a study on the drug resistance of H. pylori strains isolated from patients in Ireland and identify risk factors associated with harboring antimicrobial-resistant strains. The study utilized a combined corpus and antrum biopsy sampling approach to culture H. pylori and investigated resistance to all six antimicrobials in clinical use for H. pylori. This is an interesting study, and my minor comments are as follows:
Reviewer 2, Point 1: The methodological section requires further clarification ("Using a sterile inoculating loop, the corpus and antrum biopsies from each patient were spread onto a Columbia blood agar..."). Please specify whether the biopsy was subjected to any processing (e.g., homogenization) before inoculation.
Response: The biopsy samples were not subject to any processing before inoculation. Further details on how the biopsy samples were inoculated onto the plate have been provided in Methods section 2.3.
Reviewer 2, Point 2: The Authors demonstrated that resistance to clarithromycin, amoxicillin, and dual resistance to clarithromycin and amoxicillin (or metronidazole) were more frequently observed in strains isolated from women than men, explaining this by the more frequent treatment undertaken in this group. However, the reader will be interested in a more in-depth analysis of this phenomenon. In other words, what else, besides more frequent treatment, could explain these observations? Could it be related to lower eradication rates, metabolic factors, physiology, immune response, bacterial load, or simply to random sample selection? Is there evidence of such gender-specific observations in the literature? Without this analysis, it is difficult to agree with the statement that "female sex was associated with an increased risk of resistance."
Response: We thank the reviewer for this valuable suggestion. We have included further discussion on the risk of antibiotic resistance in H. pylori from females versus males in the revised manuscript, as well as supporting references 53-64 and 66-69.
Reviewer 2, Point 3: Table 6 should be placed in the "Results" section, not in the Discussion.
Response: Table 6 has been moved to the Results section.
