PONE-D-20-22429

The Growing Role of Streptococci as Causative Agents of Peritoneal Dialysis-related Peritonitis. A Longitudinal Analysis

PLOS ONE

Dear Dr. Fontan,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.  Those points are included below.

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Sean Reid

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Overview

The authors have conducted a 30-year retrospective chart review to evaluate trends in incidence of PD-related peritonitis. They have found decreasing trends in staphylococci and Gram negative bacterial infections and an increase in streptococcal and polymicrobial infection. There wasn’t a difference in predictive risk factors for Streptococcal PDrP but had more favorable outcomes. There were no differences amongst species of Streptococci. This is information that is useful to clinicians, infection prevention and improving quality of care. The authors have described the various aspects of this study succinctly and performed an excellent review of why this is an issue of practical importance. They also highlight, the potential difficulties with interpreting this data due to the retrospective nature of the work many years later.

Importance

The submission is an important contribution as it highlights important etiological trends in PDrP and advocates for further research towards preventing streptococcal and polymicrobial infections.

Abstract

Appropriate wording and description.

Throughout the manuscript, period has been replaced by a comma probably related to a software issue – example please change 1,6% to 1.6%

Please reword “We disclosed significant trends to a decrease” and “The last three decades have contemplated a growing involvement”.

Throughout the manuscript, please replace “associated a” with “was associated with a”

Introduction

Written well. No significant changes recommended.

Please reword the last paragraph as it is wordy and unclear “Our main interest was to pursue a clinical perception that advances in the prevention and management of PDrP could have modified the clinical scenery of PD-related peritonitis, conferring streptococci a progressively dominant role, with potential consequences for the clinical presentation, management and outcomes of these infections.”

Methods

The general design, study variables and outcomes are appropriate.

Please delete “(primary objectives too)”

Is information regarding methicillin resistance available for Staphylococcus aureus? If so, please include it. If not available, please note that it is not available.

Describe outpatient diagnosis, and management of PDrP and if any changes have been made over the last 30 years. Since hospital admission for PDrP is indicated for high-risk patients, infections with an aggressive clinical presentation, treatment failure after oriented antimicrobial therapy and isolation of microorganisms demanding in centre management – what is the management for those that don’t meet these criteria? Are cultures obtained prior to empiric therapy as an outpatient? This may have a significant impact on epidemiology, etiology, presentation and outcomes.

Are chlorhexidine baths/ wipes used for any patients?

Please cite SPSS per guideline

Results

Four hundred and sixty-two patients (52.6%) suffered at least one episode of PDrP. This appears to be inconsistent.

To clarify, did 462 out of 878 patients evaluated have a total of 1061 episodes of PDrP? If so, could this be stated more clearly for the reader?

Antibiotic association should be delineated better. Is the implication deviation from standard practice?

Clinical outcomes are described in an excellent manner.

Discussion

Well described. No significant changes recommended.

Given the suspicion for enteric source due to Streptococcal, polymicrobial and Gram negative infections even after exclusion of an obvious surgical etiology, it may help to include how many of these instances had negative abdominal imaging (if information available).

With streptococcal PDrP, could presentation be delayed due to a sub-acute onset of illness and therefore present with a higher PD fluid cell count?

Acknowledge limitation that therapy used may be broader than necessary for streptococcal PDrP. Since this paper evaluates outcomes, this may be important.

Limitations:

Overall, well described.

References:

Appropriate.

Table 1-7; Figure 1

Clear and appropriately defined. For figure, can consider trend line chart.

Reviewer #2: The authors have studied the incidence and characteristics of peritonitis over a 30-year period.

The paper is interesting, but there are a few problems with the analysis.

1) The authors seem to fall between two stools in their methodology. The stated aim is particular focus on streptococcal infections, but they present data on all common forms of peritonitis, so it is only in the discussion that any real differences in approach appear. Consider altering the focus to a general overview of the peritonitis experience (the most interesting choice for this reviewer). I am not clear why they have chosen streptococci as the primary subject of investigation. If they wish to maintain the focus on streptococci, perhaps just comparing streptococci with “all others”.

2) The incidence of streptococcal infections is more or less unchanged, varying between 0,063 and 0,122/year for a relatively small number of cases. This is confirmed by the joinpoint analysis. The title is thus somewhat misleading, and could really be called “The falling incidence of staphylococci…..”. The relative incidence of streptococci and staphylococci is uninteresting in this respect.

3) Several of the variables do not seem to be normally distributed, e.g. Charlson Comorbidity score, peritoneal cell count, time to remission or catheter removal, but are presented and analysed as such in the multivariate analyses.

4) Some of the statistics “feel” wrong. E.g an unchanged Strept. peritonitis incidence translates into a 77% increase in Table 4. A more or less identical time to remission is significant in Table 6. Please check for common statistical errors (maybe using professional statistical assistance), e.g. failing to correct for multiple comparisons, using parametric analyses for non-parametric variables, treating categorical variables as continuous variables.

Minor Comments

1) Page 8 ” including 25 patients (15,8%) with more than two monobacterial streptococcal PDrP during follow-up (range 3-7).” Slightly unclear. 3-7 months? What about patients with two monobacterial streptococcal PDrP during follow-up?

2) Page 9. “Median delays to the first episode of PDrP were 8 (interquartile range 3 to 17) (overall) and 12 months (interquartile range 5 to 24)(streptococcal PDrP).” Does “overall” include or exclude streptococcal PDrP?

3) Page 9 “On the other hand, at least one streptococcal strain was isolated in 78 polymicrobial infections”. Table 2 seems to state 116 patients. Unclear, please clarify.

4) “No patient denied consent”. In this long-term retrospective study, requirement for patient consent was presumably waived?

5) Table 4. Four outcomes are defined in the Methods, but only three are presented. Were the outcomes censored for each other?

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-20-22429_reviewer with highlights.pdf

PONE-D-20-22429R1

The Growing Role of Streptococci as Causative Agents of Peritoneal Dialysis-related Peritonitis. A Longitudinal Analysis

PLOS ONE

Dear Dr. Fontan,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.  Specifically, one reviewer is at odds with your conclusions.  I would like you to review these comments and indicate whether or not the minor changes proposed are reasonable. 

Please submit your revised manuscript within two weeks. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Sean Reid

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The authors have responded satisfactorily to previous comments.

I have only one remaining issue.

The bottom line is that no significant change in incidence of streptococcus peritonitis has ocurred. Thus the title "The Growing Role of Streptococci as Causative Agents of Peritoneal Dialysis-related Peritonitis." and the conclusion "Streptococci have acquired an increasing role as causative agents" are misleading.

It is not usual to present an insignificant trend as a conclusion Indeed, in the opinion of this reviewer, a more scientific title would be “Unchanged incidence of streptococcal peritonitis over a 30-year period”, but at the very least it should be emphasised that it is relative and not absolute incidence that is being discussed. As previously stated, the emphasis on relative incidence is not very interesting.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Long-Term Trends in the Incidence of Peritoneal Dialysis-Related Peritonitis Disclose an Increasing Relevance of Streptococcal Infections. A longitudinal Study

PONE-D-20-22429R2

Dear Dr. Fontan,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Sean Reid

Academic Editor

PLOS ONE

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