Peer Review History

Original SubmissionJuly 1, 2022
Decision Letter - Iddya Karunasagar, Editor

PONE-D-22-18648Risk factors and microbiological features of recurrent Escherichia coli bloodstream infectionsPLOS ONE

Dear Dr. Park,

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.

Please address comments on the manuscript and improve presentation of Table 1. 

Please submit your revised manuscript by Oct 02 2022 11:59PM. 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Iddya Karunasagar

Academic Editor

PLOS ONE

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Additional Editor Comments:

The reviewer has many important comments to improve the manuscript. Please revise considering all comments point by point.

[Note: HTML markup is below. Please do not edit.]

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

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

Reviewer #1: 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: 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

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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: The authors hve carried out a retrospective analysis of Esch.coli BSI with recurren and re-infection and have compared resistance and virulence genes.

As it is a retrospective study, details of how the folow up data was collected needs to be exlained.s

No where have the authors juxtaposed the different resistance or virulence genes among the groups,to compare. with an appropriate statistical test.

Table 1. just lists the various genes. This may be modified to a comparative table.

Minor points have been highlighted in the attached manuscript.

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6. 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.

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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: Yes: Reba Kanungo MD,PhD Former Dean Research & HoD Microbiology ,PIMS,Puducherry, India

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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.

Attachments
Attachment
Submitted filename: PONE-D-22-18648_reviewed.pdf
Revision 1

To editor,

Thank you for your constructive comments and criticism on our manuscript. The manuscript has been carefully rechecked and appropriate changes have been made in accordance with the journal requirements and the reviewers’ suggestions. We believe that the quality of the manuscript has significantly improved after incorporating the reviewers’ suggestions. Our point-by-point responses to the reviewers are provided in the “Response to reviewers” file. Furthermore, we have ensured that the manuscript meets PLOS ONE's style requirements. We have now provided the original (uncropped and unadjusted) images of the underlying gel results reported in Fig 2, as S1 Fig.

We hope that the revised manuscript is now suitable for publication in your journal. We look forward to your response.

================================================================================================================

Response to Reviewer

We thank the reviewer for their thoughtful comments and suggestions, which have enhanced the manuscript and produced a balanced account of the research.

Reviewer #1:

Comment #1

As it is a retrospective study, details of how the follow up data was collected needs to be explained.

Authors’ response to comment #1>

To address your comment. The Department of Laboratory Medicine in Ilsan Hospital, where this study was conducted, has been collecting E. coli strains that caused bloodstream infection for research. Since they were not specimen of human origin, informed consent was not required from the subjects for collection. Patients’ information related to E. coli strains was collected retrospectively through medical records.

Comment #2

No where have the authors juxtaposed the different resistance or virulence genes among the groups,to compare. with an appropriate statistical test.

Table 1. just lists the various genes. This may be modified to a comparative table.

Authors’ response to comment #2>

Please verify whether your comment is about Table 4 and not Table 1. If you are referring to Table 4, we could not compare antimicrobial resistance genes, plasmid types, and virulence factors detected in each of the ESBL-producing E. coli isolates from each of the different BSI groups due to limited numbers of isolates included in the WGS test.

Therefore, we decided to present Table 4 as supplementary data (S2 Table). We further describe this limitation in the “Discussion” section, as follows (Page 17, Line 322–326):

“Third, we could not compare antimicrobial resistance genes, plasmid types, and virulence factors detected in each of the ESBL-producing E. coli isolates from each of the different BSI groups due to limited numbers of isolates included in the WGS test. Further studies are needed to provide more information on molecular characteristics of ESBL-producing E. coli causing BSI.”

Comment #3

Minor points have been highlighted in the attached manuscript.

-There is no shortening in “Short Title”

Authors’ response to comment #3>

We agree and we have revised the short title, as follows:

“Recurrent Escherichia coli bloodstream infections”

Comment #4

Minor points have been highlighted in the attached manuscript.

-Grammar error in “Abstract”

Authors’ response to comment #4>

We concur and we have corrected the sentence as follows (Page 3 Line 31–32):

Original: “We also identify the ST131 and ESBL genotype to…”

-> Revised: “We also identified the ST131 and ESBL genotype to…”

Comment #5

Minor points have been highlighted in the attached manuscript.

-What statistical test was applied to note significant differences in Table 3?

Authors’ response to comment #5>

We acknowledge your detailed comment. To address your comment, we performed a statistical test.

We also modified the manuscript according to the statistical test result (Page 12, Line 210–215).

Original: “ST131 strains were more frequently observed in the early onset group (N = 12, 41.4%) when compared to the late onset recurrent episode (N = 7, 25.0%) and single episode (N = 34, 22.8%) groups. E. coli with an ESBL genotype were also more commonly observed in the early onset recurrent episode (N = 12, 41.4%) group when compared with either the late onset recurrent episode (N = 7, 25%) or single episode BSI (N = 25, 16.8%) groups.”

-> Revised: ‘ST131–025 strains were more frequently observed in the early onset group (N = 12, 41.4%) when compared to the late onset recurrent episode (N = 6, 21.4%) and single episode (N = 29, 19.5%) groups (P = 0.036). E. coli with an ESBL genotype were also more commonly observed in the early onset recurrent episode (N = 12, 41.4%) group when compared with either the late onset recurrent episode (N = 7, 25%) or single episode BSI (N = 25, 16.8%) groups (P = 0.011).”

Attachments
Attachment
Submitted filename: Response to reviewers.docx
Decision Letter - Iddya Karunasagar, Editor

PONE-D-22-18648R1Risk factors and microbiological features of recurrent Escherichia coli bloodstream infectionsPLOS ONE

Dear Dr. Park,

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.

==============================

Please provide clarifications for patient consent and add limitation of the study. 

==============================

Please submit your revised manuscript by Dec 09 2022 11:59PM. 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Iddya Karunasagar

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Please clarify regarding patient consent and add a note on the limitation of the study.

[Note: HTML markup is below. Please do not edit.]

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

**********

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: Partly

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

Reviewer #1: 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: 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

**********

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: Minor revision is required with regards to the following

1. E. coli strains that caused bloodstream infection for research. Since they were not specimen of human origin, informed consent was not required from the subjects for collection� How did this reflect BS infections in specific patients ?

However the following stamen is contradictory: Our study cohort consisted of adult patients (age ≥18 92 years) who presented at the Ilsan Hospital with positive blood cultures for E. coli at least 93 once over the course of a two-year period.

Was any permission sought and granted from the hospital authorities to use patient data? If so this must be mentioned.

2. The paper still lacks in clarity with regards to the genetic studies on resistance and recurrence outcome . This may be highlighted .

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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

**********

[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.

Attachments
Attachment
Submitted filename: PLOS-Risk factors and microbiological features.docx
Revision 2

We thank the editor and reviewers for their thoughtful comments and suggestions, which have enhanced the manuscript and produced a balanced account of the research.

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Authors’ response>

We have reviewed and changed the reference list. We found that reference numbers 12 and 14 were duplicated, so we corrected the reference number after deleting one of them. These changes were also applied to the introduction, methods, results, and discussion.

Additional Editor Comments:

Please clarify regarding patient consent and add a note on the limitation of the study.

Authors’ response>

In response to the reviewer’s comments, statements regarding patient consent and descriptions of the limitation of this study are listed below.

Reviewer #1:

Comment #1

E. coli strains that caused bloodstream infection for research. Since they were not specimen of human origin, informed consent was not required from the subjects for collection� How did this reflect BS infections in specific patients ?

However the following stamen is contradictory: Our study cohort consisted of adult patients (age ≥18 92 years) who presented at the Ilsan Hospital with positive blood cultures for E. coli at least 93 once over the course of a two-year period.

Was any permission sought and granted from the hospital authorities to use patient data? If so this must be mentioned.

Authors’ response to comment #1>

We regret to inform you that there were errors and omissions in our prior explanation.

E. coli strains identified in blood culture were of human origin. However, since bacteria isolated from the human body do not contain the genetic information of humans, there are no restrictions on the collection or use of the collected strains. This matter is addressed in detail in the bylaws of the Institutional Review Board (by which this study was approved). Young Ah Kim (Department of Laboratory Medicine at Ilsan Hospital) harvested several strains isolated from blood culture, including E. coli for another study. E. coli strains analyzed for this study were already collected and matched with the ID number of patients, who had experienced bloodstream infections (BSIs) due to corresponding strains. Therefore, clinical information on patients with BSIs caused by a specific strain could likewise be obtained through a medical record review. The aforementioned information was disclosed when receiving the Institutional Review Board approval for this study.

Comment #2

The paper still lacks in clarity with regards to the genetic studies on resistance and recurrence outcome. This may be highlighted.

Authors’ response to comment #2>

We attempted to evaluate the genetic characteristics of ESBL-producing E. coli strains from each of the different BSI groups and determine the effects of genetic factors on recurrence. However, we could not determine the effect of antimicrobial resistance genes, plasmid types, and virulence factors detected in ESBL-producing E. coli isolates on recurrence due to the limited number of isolates included in the WGS test.

We further describe this limitation in the “Discussion” section of the paper (Page 17, Line 322–326):

“Third, we could not determine the effect of antimicrobial resistance genes, plasmid types, and virulence factors detected in ESBL-producing E. coli isolates on recurrent BSI due to limited numbers of isolates included in the WGS test. This limitation precluded comprehensive and accurate explanation for genetic characteristics of E. coli causing recurrent BSI.”

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Iddya Karunasagar, Editor

Risk factors and microbiological features of recurrent Escherichia coli bloodstream infections

PONE-D-22-18648R2

Dear Dr. Park,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Iddya Karunasagar

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All reviewer comments have been addressed satisfactorily.

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

**********

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

**********

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

Reviewer #1: 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: 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

**********

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: The comments to the reviewer's queries have been adequately responded.and ncessary changes have been made in the manuscript

**********

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

**********

Formally Accepted
Acceptance Letter - Iddya Karunasagar, Editor

PONE-D-22-18648R2

Risk factors and microbiological features of recurrent Escherichia coli bloodstream infections

Dear Dr. Park:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Iddya Karunasagar

Academic Editor

PLOS ONE

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