PONE-D-20-05909

Four weeks versus six weeks of ampicillin plus ceftriaxone in Enterococcus faecalis native valve endocarditis: A prospective cohort study.

PLOS ONE

Dear Dr. Ramos,

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 submit your revised manuscript by Jul 10 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Cécile Oury

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide the full names of the Institutional Review Boards s that approved the study in your manuscript.

3. Please specify in your ethics statement whether participant consent was written or verbal. If verbal, please also specify: 1) whether the ethics committee approved the verbal consent procedure, 2) why written consent could not be obtained, and 3) how verbal consent was recorded.” Do not ping with follow up unless there are questions

4. Thank you for stating the following in the Acknowledgments Section of your manuscript:

'This work was supported in part by the “Fondo de Investigaciones Sanitarias” (FIS)

grant 17/01251 from the “Instituto de Salud Carlos III”, Madrid, Spain awarded to

JMM. JMM received a personal 80:20 research grant from the Institut d’Investigacions

Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19. JMP was

member of the Endocarditis Team of the Hospital Clinic of Barcelona, Spain when this

project was approved by the GAMES Steering Committee.'

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

'The funders had no role in study design, data collection and analysis, decision to

publish, or preparation of the manuscript.'

5. Thank you for stating the following in the Competing Interests section:

'Dr. Ramos-Martínez declares personal fees from Merck, Astellas and Pfizer, outside

the submitted work. Dr. Ojeda-Burgos reports personal fees from Merck, personal fees

from Janssen Cilag, personal fees from Gilead, outside the submitted work. Dr. Miro

reports grants and personal fees from AbbVie, Bristol-Myers Squibb, Contrafect,

Genentech, Jansen, Medtronic, Merck, Novartis, Gilead Sciences, and ViiV Healthcare,

outside the submitted work. Dr. Juan M Pericas. Dr. Ana Fernández-Cruz, Dr. Patricia

Muñoz, Dr. Maricela Valerio, Dr. Martha Kestler, Dr. Miguel Montejo, Dr. Mª Carmen

Fariñas, Dr. Dolores Sousa, Dr. Fernando Domínguez, Dr. Antonio Plata and Dr. Laura

Vidal have nothing to disclouse'

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

6. Please amend the manuscript submission data (via Edit Submission) to include author Guillermo Ojeda-Burgos MD PhD

Additional Editor Comments (if provided):

[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

**********

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

Reviewer #1: No

**********

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

**********

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

**********

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: Dear authors,

Your work addresses an important clinical issue with regard to treating patients with NVEFIE. Interesting work.

Major issues:

1. Statistical issue: p8, 202-204. It is stated that continous varibales will be reported as a median with IQR and that a student's t-test will be used to compare these values. If you report values as a median with IQR, it means that your data was not normally distributed. Did you check if the continous variables had a normal distribution? In that case, it is not correct to use a student's t-test and a non-parametric test should be used.

2. Statistical issue: p8, 204. The aim of this study is to test whether the clinical outcome of patients that received AC for 4 weeks is similar to those that received AC for 6 weeks. Student t-tests are made to test if there is a significant difference, not to test equivalance. Did you perform an equivalence test or can this be conducted?

3. p3, 100-101. In the abstract you mention that patients that received AC for 4 weeks had a longer duration of symptoms (21 days) than patients thet received AC for 6 weeks (7 days). In table 1, the values are the opposite. Is this a mistake? Should be corrected, because it is concluded that treatment with AC for 4 weeks may be considered in patients with a shorter duration of symptoms.

Minor issues:

4. Does severity of symptoms correlate with a worse outcome? For example, perivalvular abscesses, vegetation size, valve perforation, ...

5. Data represented in table 1 will be more clear if this table is divided in to two tables: one with the baseline characteristics and another one with the data on outcome.

**********

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.

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.

Four weeks versus six weeks of ampicillin plus ceftriaxone in Enterococcus faecalis native valve endocarditis: A prospective cohort study.

PONE-D-20-05909R1

Dear Dr. Ramos,

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,

Cécile Oury

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: