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PONE-D-21-28267Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: a case-control studyPLOS ONE

Dear Dr. Qu,

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. In particular, reviewer 1 thinks more information is needed for "the selection of the case and control group," and tables need to be improved. Therefore, I recommend you revise your manuscript by addressing those review comments.

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Taeok Bae

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: No

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: I Don't Know

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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: The authors performed a retrospective case-control study to compare clinical characteristics and outcome of PVL+ and PVL- S. aureus bacteremia. The premise of the study is interesting, since PVL has been associated with SSTI and pneumonia but its relevance in S. aureus bacteremia (SAB) is still unclear. In total, 52 case and 56 control patients were included and analyzed. The authors concluded that the clinical cure was comparable and that the presence of PVL does not have any significant effect on the clinical course of SAB.

In order to assess the methodological quality of the paper, some missing information needs to be provided/clarified.

Major comments:

• In the selection of the case/control, was the antibiotic taken into account? The (optimal) treatment for MRSA SAB and MSSA SAB are not the same. MRSA=vancomycin and MSSA=beta-lactams/oxacillin. That being said, the proportion of MRSA/MSSA in both case and control groups were unclear. This information (and statistics) should be included in the tables. This is an essential information as vancomycin has been demonstrated to be inferior in terms of clinical cure (which is the outcome in the study) than oxacillin for treating MSSA SAB.

• In the US, most PVL+ strains are MRSA (ST8 USA300). Therefore, PVL- MRSA controls would have been the best choice of control group (or at least equal proportions of MRSA/MSSA). In the study 77% of the cases were MRSA and only 29% of the control was MRSA. Did all patients in both groups receive the same antibiotic treatment (vancomycin)?

• Tables are not intuitive. For example, table 6. How were the categories for vancomycin determined? Were these vancomycin plasma levels? If yes, units are missing and please state so. I assume that N=number of patients (e.g. for Vancomycin categories). It was unclear how the numbers in the column should add up (Total IVDU users N=30; but VAN <0.5 N=27; 1 N=38 and 2 N=5 giving a total of N=70)? Similar to outcome of infection (16+4+16 does not add up to N=30/column total). Please check your tables and numbers. Missing values and others should be included in the tables.

• These points should be clarified before other aspects of the study can be assessed.

Minor points

• Line 58: gene in italics

• Line 62: please cite the correct papers. Papers cited did not show the increase of ST8-USA300 in the community worldwide! (e.g. PMID: 30315958, 34160741, 26884428, 26464204, 33636329, etc..)

• Line 67: please cite the correct papers. Pneumonia PMID: 10524952, SSTI/Abscesses PMID: 25753191.

• Line 100: bacterial genus/species in italics

• Line 156: explain the coding of vancomycin

• Lines 211: length of stay, fever and other clinical parameters can only be assessed if information on the antibiotic therapy was provided (choice of antibiotic has an effect on the clinical course)

Reviewer #2: In the manuscript “Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: a case-control study” authors describe the possible differences in clinical outcomes for SAB associated with the presence and absence of the PVL exotoxin. The manuscript presents interesting data, it is well structured and the writing quality is good.

Minor comments:

1. Line 39: correct percentage of MRSA in case patients

2. Please correct the order of tables (table #6 is after the table #3, and #4 is after #6)

3. Line 243: correct spelling of “however”

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Reviewer #1: Yes: Dennis Nurjadi

Reviewer #2: No

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Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: a case-control study

PONE-D-21-28267R1

Dear Dr. Qu,

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.

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Kind regards,

Carla Pegoraro

Division Editor

PLOS ONE

Additional Editor Comments (optional):

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

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

Reviewer #1: Yes

Reviewer #2: N/A

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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

Reviewer #2: Yes

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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: thank you for addressing the reviewers' comments, no further comments or concerns for the revised manuscript from my side.

Reviewer #2: (No Response)

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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