Bacterial Gastrointestinal Infections in Pediatric Inflammatory Bowel Disease (PIBD)—A Single-Center Experience of Epidemiology, Management, and Outcome

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for submitting the manuscript „ Bacterial gastrointestinal infections in pediatric inflammatory bowel disease (PIBD) – a single-center experience on epidemiology, management, and outcome“. The manuscript covers interesting and important topic of infections in IBD, and it reflects a huge amount of work. However, there are some points that need to be addressed:

1. Introduction

- regarding: „Although the ECCO guidelines[7] on opportunistic infections in IBD are not specifically tailored to PIBD patients, the ESPGHAN IBD Porto Group considers them largely applicable.[6]“ – ESPGHAN recommendations (cited ref 6) were published in 2012 so they cannot refer and consider applicable ECCO guidelines pubilshed in 2021

- consider providing a flowchart of the study

3. Results

- when mentioning for the first time, please use the whole name for K. oxytoca, C. jejuni, S. Enteritidis

- how many patients in total were diagnosed with IBD in the study period – what was the proportion of the patients with infections

- it would be interesting to see where there any differences between the groups with diagnosed infection vs those who were screened for infection, but the tests were negative

- consider conducting statistical analysis

Discussion

- Regarding „Evidence from previous IBD studies indicates that infection risk is increased in patients treated with infliximab, particularly at shortened dosing intervals, and in those receiving corticosteroids.[7, 8, 18] – reference 18 does not show that the infection risk is increased in patients treated with infliximab

- In general, it is not advisable to compare results presented as majority or rarely (with not known statistical significance) with the results of other studies

- Making conclusions on data without showing whether there is a statistical difference could be misleading

References

- following references seem incomplete or not cited correctly: 2, 5, 13, 18, 20

Author Response

Reviewer 1:

Thank you for submitting the manuscript „ Bacterial gastrointestinal infections in pediatric inflammatory bowel disease (PIBD) – a single-center experience on epidemiology, management, and outcome“. The manuscript covers interesting and important topic of infections in IBD, and it reflects a huge amount of work. However, there are some points that need to be addressed:

1. Introduction

Q: regarding: „Although the ECCO guidelines [7] on opportunistic infections in IBD are not specifically tailored to PIBD patients, the ESPGHAN IBD Porto Group considers them largely applicable.[6]“ – ESPGHAN recommendations (cited ref 6) were published in 2012 so they cannot refer and consider applicable ECCO guidelines published in 2021 -

A:  We thank the reviewer for this important comment. We have revised the corresponding statement in the Discussion to better reflect the evolution of evidence and current guideline recommendations.

Q consider providing a flowchart of the study 

A: We added a flowchart accordingly

1. Results

Q: when mentioning for the first time, please use the whole name for K. oxytoca, C. jejuni, S. Enteritidis

A: We aligned this according to the suggestion

Q: how many patients in total were diagnosed with IBD in the study period – what was the proportion of the patients with infections 

A: Of the 139 patients screened, 87 were diagnosed with IBD during the study period (2011–2021). Among the 17 infection episodes observed in 14 patients, 12 occurred in patients who received their IBD diagnosis within the study period.

 

Q: it would be interesting to see where there any differences between the groups with diagnosed infection vs those who were screened for infection, but the tests were negative

A: comparison between patients with confirmed infections and those with negative microbiological testing was not feasible due to the retrospective design and lack of systematic data collection in the latter group, but represents an important area for future research.

Q: consider conducting statistical analysis 

A: We thank the reviewer for this suggestion. Given the small sample size, advanced statistical analyses such as regression modeling were not considered appropriate. However, we have strengthened the statistical presentation by adding descriptive statistics, including percentages and 95% confidence intervals for key outcomes.

Discussion

Q: Regarding „Evidence from previous IBD studies indicates that infection risk is increased in patients treated with infliximab, particularly at shortened dosing intervals, and in those receiving corticosteroids.[7, 8, 18] – reference 18 does not show that the infection risk is increased in patients treated with infliximab

A: We thank the reviewer for this important observation. We agree that the TREAT registry does not identify infliximab as an independent risk factor for serious infections after adjustment, with corticosteroid use being the main driver of risk. We have revised the statement accordingly and removed this reference to ensure a more accurate and balanced interpretation of the available evidence.

Q: In general, it is not advisable to compare results presented as majority or rarely (with not known statistical significance) with the results of other studies -> diskutabel

A: We thank the reviewer for this important comment. We agree that comparisons based on descriptive terms such as “majority” or “rarely” without statistical testing should be interpreted with caution. We have changed this accordingly.

Q: Making conclusions on data without showing whether there is a statistical difference could be misleading

A: We thank the reviewer for this important comment. We agree that conclusions should not overstate findings in the absence of statistical testing. We have aligned this accordingly.

Reviewer 2 Report

Comments and Suggestions for Authors

The scientific question raised by authors is very pertinent to bridge the knowledge gap. I have certain comments

major

1. the aim of the study can be made discrete and very specific. too many questions can lead to cluttered findings.
2. similarly the primary and secondary objectives of the study needs refinement and presentation of these objectives can be improved in results.
3. consider using STROBE checklist for presentation of work to improve objectivity
4. Is univariate and multivariate analysis possible to determine the susceptibility to infection
5. did authors find any viral, fungal, and protozoal infections that  caused IBD flares. should they be mentioned in exclusion? 

Minor

1. avoid interpretation in result section
2. phenotypes of UC and CD may be added and baseline characteristic of IBD can be presented in a table with data on type of IST
3. discussion section can present more data for comparison on prevalence of bacterial superinfection. use percentage to create impact wherever possible and comparison of data is made
4. strength and limitation section can be more elaborate

Author Response

R2:

The scientific question raised by authors is very pertinent to bridge the knowledge gap. I have certain comments

major

1. the aim of the study can be made discrete and very specific. too many questions can lead to cluttered findings.

A: We agree that clearly defined study aims are important. Our study was designed as a descriptive analysis of bacterial gastrointestinal infections in pediatric IBD, focusing on epidemiology, clinical presentation, management, and outcomes, which we consider closely interrelated aspects of the same clinical entity. To improve clarity, we have slightly refined the wording of the study aim in the manuscript.

1. similarly the primary and secondary objectives of the study needs refinement and presentation of these objectives can be improved in results.

A: We have refined the presentation of the study objectives by clearly defining primary and secondary objectives in the Introduction. The primary objective was to characterize the epidemiology and clinical features of bacterial gastrointestinal infections in pediatric IBD, while secondary objectives included the assessment of management strategies and clinical outcomes. In addition, we have slightly revised the Results section to better align with these objectives.

1. consider using STROBE checklist for presentation of work to improve objectivity –

A: We thank the reviewer for this valuable suggestion. We have ensured that the manuscript is aligned with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines and have added a corresponding statement in the Methods section

1. Is univariate and multivariate analysis possible to determine the susceptibility to infection

A: Due to the small sample size and the descriptive design of our study, univariate and multivariate analyses to identify risk factors for infection were not considered appropriate, as such analyses would lack sufficient statistical power and could lead to unreliable or misleading results. We agree that investigating susceptibility to infection using multivariable approaches would be of great interest and should be addressed in larger cohorts or multicenter studies in the future

1. did authors find any viral, fungal, and protozoal infections that caused IBD flares. should they be mentioned in exclusion?

A: The present study was specifically designed to investigate bacterial gastrointestinal infections in pediatric IBD, and systematic screening for viral, fungal, or protozoal infections was not performed. Therefore, such infections were not included in the analysis. We agree that these pathogens may also contribute to IBD flares and represent an important area for future research. This aspect has been added to the limitations section of the manuscript.

Minor

1. avoid interpretation in result section

A: The results section has been revised to ensure a strictly descriptive presentation of the data, and interpretative statements have been removed or relocated to the Discussion section.

1. phenotypes of UC and CD may be added and baseline characteristic of IBD can be presented in a table with data on type of IST 

A: A table with phenotype and type of IST was added

1. discussion section can present more data for comparison on prevalence of bacterial superinfection. use percentage to create impact wherever possible and comparison of data is made.

A: We have revised the Discussion to replace qualitative terms (e.g., “most” or “majority”) with quantitative data (percentages) to improve clarity and impact. Furthermore, we have added a statement comparing the observed proportion of bacterial gastrointestinal infections in our cohort with previously reported data, while emphasizing the limitations of direct comparison due to differences in study design and diagnostic strategies.

1. strength and limitation section can be more elaborat

A: We have expanded the strengths and limitations section to provide a more detailed and balanced discussion of the study’s methodological constraints and key strengths, including the retrospective design, limited sample size, lack of comparative data, and the focused assessment of bacterial infections.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for submitting the revised version of the manuscript „Bacterial gastrointestinal infections in pediatric inflammatory bowel disease (PIBD) – a single-center experience on epidemiology, management, and outcome“ and thank you for addressing most of the comments. The manuscript has been improved but there are still some points that need to be clarified:

- In Abstract in results and in the Results there are sentences that start as „14 patients…“. If the sentence begins with a number, it should be spelled out, rather than using numerals. If the number is complex or spelling out the number is awkward, the  sentence can be restructured to avoid starting it with a numeral.

References

- following references are incomplete or not cited correctly: 2, 5, 13, 18, 20 – as by the journal’s instructions – Journal title should be cited by Abbreviated Journal Name and if the book is cited than it should be cited as: Author 1, A.; Author 2, B. Book Title, 3rd ed.; Publisher: Publisher Location, Country, Year; pp. 154–196.

Author Response

Many thanks for your precise suggestions and help. We changed the manuscript accordingly.

Q: In Abstract in results and in the Results there are sentences that start as „14 patients…“. If the sentence begins with a number, it should be spelled out, rather than using numerals. If the number is complex or spelling out the number is awkward, the  sentence can be restructured to avoid starting it with a numeral.

A: This has been corrected

References

Q:  following references are incomplete or not cited correctly: 2, 5, 13, 18, 20 – as by the journal’s instructions – Journal title should be cited by Abbreviated Journal Name and if the book is cited than it should be cited as: Author 1, A.; Author 2, B. Book Title, 3rd ed.; Publisher: Publisher Location, Country, Year; pp. 154–196.

A: The format of the citations were aligned according to the suggesitions.

Reviewer 2 Report

Comments and Suggestions for Authors

authors have addressed the reviewer comments satisfactorily. 

Author Response

Many thanks for your help reviewing the manuscript.