PONE-D-23-31373Frequency and mortality rate following antimicrobial-resistant bloodstream infections in tertiary-care hospitals compared with secondary-care hospitalsPLOS ONE

Dear Dr. Limmathurotsakul,

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.

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Ali Amanati

Academic Editor

PLOS ONE

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3. During our evaluation of the documents provided, we noted that the data were accessed for research purposes in November 2022, but this was after the project period had expired on the IRB documents supplied. Please could you provide the ethics approval extension documents for the study. If the document is in another language, please also provide an English translation. Please note that if these documents are not included when your manuscript is resubmitted, it may be rejected.

4. Thank you for stating the following financial disclosure:

“The study was supported by the DDC, MoPH, Thailand, and Defense Threat Reduction Agency (DTRA), U.S.. This research was funded in part by the Wellcome Trust (224681/Z/21/Z and Wellcome Trust Institutional Translational Partnership Award-MORU). CL is supported by the Wellcome Trust (106680/B/14/Z). BS is supported by a grant from the UK Department of Health and Social Care using UK aid funding managed by the Fleming Fund (R52354 CN001). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

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Additional Editor Comments:

Dear authors

Your manuscript [PONE-D-23-31373] has passed the review stage and is ready for ‎revision. ‎

Editorial comments

To ensure the Editor and Reviewers can recommend that your revised manuscript be ‎accepted, ‎‎please pay careful attention to each comment posted underneath ‎this email. This way we ‎can ‎avoid future clarifications and revisions, moving swiftly to ‎a decision.‎

‎1. Please provide a point-by-point response to the Editor and reviewer's comments

‎2. Please highlight all the amends on your manuscript with yellow color

‎3. Some grammatical and spacing errors need to be revised throughout the ‎manuscript

Editor comments:

There are significant objections to the statistical tests applied in this study.‎

As the second reviewer has pointed out, multivariable modeling ‎needs to be considered, and as the fourth reviewer has ‎pointed out, the significance of the obtained findings may be weakened ‎substantially without controlling potential confounders for investigating differences between hospital and also investigating factors associated with mortality. Please noticed that without considering advanced statistical revision I am unable to consider the manuscript further for peer review.‎

Truly yours

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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

Reviewer #3: Partly

Reviewer #4: Partly

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: 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

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: 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

Reviewer #3: Yes

Reviewer #4: 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: Thanks to the research team for their valuable work. Please find my comments below:

1. In lines 220 to 227, you mentioned the hospitals included in the study, stating that out of 96 hospitals, 46 were excluded under certain conditions, and 49 studies were analyzed in your research, while it should have been 50. Please provide an explanation for this discrepancy regarding one study.

2. In the statistical section, it is necessary to clarify which variables have fixed effect(s) and which have random effect(s) in your mixed-effects logistic model.

3. Please be aware that p-values only indicate the level of significance, not the strength of the relationship. Therefore, consider this in all your tables and replace all values of <0.0001 with <0.001. NOTICE: "When p-values are displayed as very small numbers (e.g., 0.0001), it can be challenging for readers to quickly grasp their significance. It's more common to use the conventional format of displaying p-values as three decimal places (e.g., 0.001) for ease of interpretation."

4. The quality of your figures is significantly low, or they did not meet the desired quality in the submitted version, and I could not extract any useful information from them.. Please ensure that the figures meet the required quality standards or provide better versions in the submitted manuscript.

5. In the references section, you've used reports as sources. Please include relevant links for each reference to facilitate readers' access to the sources in your article.

Reviewer #2: I am impressed by the large amount of data collected during the study period 2012 to 2015; however, I recommend rejection due to the limited analysis performed and the similarities with previous studies.

Reviewer #3: Dear Authors

Kindly address the following few concerns

Line 154 correct the grammatical error " local importance" instead of "locally importance."

Line 215, second sentence is unclear, kindly revise.

LINE 398 "This is likely occurring in other LMICs” as part of the conclusion is too much of extrapolation from the current study under review. Rephrasing it to eg “This may be situation in other LMICs, or This might also be occurring in other LMICs” will be more scientifically acceptable.

Additional concerns

1. please include a section/paragraph that describes challenges or weakness or limitations of this study.

2. Are the patients' demographics accessible? We could make more meaningful inference from the comparative analysis with the demographic data. If this is not available, kindly include it in the weakness section.

Reviewer #4: Review of the manuscript frequency and mortality rate following antimicrobial-resistant blood stream infection in tertiary care hospital compared with the secondary care hospital.

This study addresses an important topic comparing the burden of antimicrobial resistant bloodstream infections between tertiary care and secondary care hospitals in Thailand. The study demonstrates the utility of using automated tools like AMASS for analyzing routine surveillance data to generate useful statistics on AMR infections. However, there are some limitations that should be acknowledged:

Major Comments:

1. More details needed on the data analysis plan - which specific metrics were compared between tertiary and secondary care hospitals and what statistical tests were used.

2. The results section overall is well-written, but could benefit from some sub-headings to improve readability by breaking it down into logical sections.

3. One limitation as acknowledged is that the findings may not be generalizable to other LMIC settings, so it may be useful to explicitly state this in the conclusion as well.

4. The paper does not provide information on the specific criteria used to classify community-origin and hospital-origin bloodstream infections (BSI), which may affect the accuracy of the results. Based only on admission date fails to account for healthcare exposures prior to admission. This could inflate community proportions at teaching hospitals receiving many transfers e.g. Patient with MRSA blood stream infection from previous hospitalization. More granular exposure data is needed

5. Designation of the Health care originated or associated blood stream infection relies on the fact that cultured organism should not be isolated from any site other than blood in order to be classified as BSI(blood stream infection) (www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf) during the infection window period. Absence of information about the culture results during the infection window period (with same organism) from sites other than blood can overestimate the proportion of blood stream infections

6. Major potential confounders like antibiotic usage, infection control practices are not adjusted for. This limits the ability to draw causal inferences about differences between hospital types.

7. Crude mortality rates do not adjust for important risk factors and likely oversimplify differences between complex tertiary vs general hospitals. More rigorous statistical approaches are needed to control for confounding

8. Relying on routinely collected data presents various quality issues like missing/inconsistent variables, coding errors, and variability in diagnostic/prescribing practices between sites. This reduces ability to accurately measure and compare burdens.

9. No validation is reported of automated classification (e.g. AMR vs susceptible). Misclassification bias could differentially affect estimates between settings

Minor Comments:

1. Standardize the formatting of abbreviations - write out full forms initially before introducing abbreviations.

2. Carefully proofread the manuscript to correct any minor grammar, spelling or punctuation errors.

3. Sample sizes: with only 15 TCHs and 34 SCHs, the study may be underpowered to detect some differences, especially for less common organisms. Larger multi-year datasets could provide more robust comparisons.

4. The study does not provide information on the specific interventions or strategies that could be implemented to address the differences in AMR burden between TCHs and SCHs.

5. The term AMR is not defined clearly whether it refers to an organism resistant to multiple families of antibiotics or just one

6. Mortality measures: all-cause in-hospital deaths only capture a fraction of outcomes and underestimate AMR impacts. Longer term and attributable mortality should also be examined.

7. Proportional measures like AMR proportions do not account for differences in total case volumes between hospitals. Higher proportions may still represent lower absolute burdens at smaller hospitals. Frequencies provide more clinically meaningful comparisons but are still prone to biases from differences in populations served.

8. Focus is on bacteremia but AMR impacts many infection types. Generalizing findings may overlook reservoir/transmission dynamics across all healthcare-associated infections.

Specific Comments:

1. Line 95-100 : The concept provided is misinterpreted , actually the reason for expressing the rates in 100s, 1000s or even 100000 is to provide the utility of comparison of rates across different locations and cohorts regardless of the size or services of the hospital https://www.cdc.gov/STD/Sassi/Module2/expression_of_rates.html

2. Line 181-192: it is not clear whether the BSI with common commensals are included in the analysis or not. according to CDC, 2 or more blood samples collected with common commensals and clinical picture constitutes BSI www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf

3. Line 194-200: the statistical analysis portion need elaboration as which of the strata of have less than 5 observations. There is mention of many statistical analysis. Author needs to clarify the data type used and rationale of using the statistical analyses.

4. Line 305-319: the text is out of the context of study as the study is about the frequency , proportion and burden of blood stream infections

5. Line 324-326: there is no assessment of AMS program or the infection control program for the participating facilities. So author cannot suggest if the practices are not tailored according to the scope of services already.

6. Line 338-343: this highlight the need of robust and comprehensive data collections that captures all aspects of patient detail including the previous admission history and the previous culture results

7. Line 344-349: no reference or bases provided for the assumptions

8. Line 354-256: contradicting statement to the earlier statement in line 324-326

9. Line 390-392: it could be overestimated as well. Since only the first isolate is taken into account there is no knowledge of how well the patient responding to the antibiotics and could die of cause other than BSI.

In summary, while a pragmatic first step, the methods have limitations for making robust policy inferences about AMR burdens in different hospital contexts. Greater standardization and more sophisticated statistical analyses are needed. Prospective collection of clinical and microbiological data would allow for more rigorous analyses of differences in AMR burdens and outcomes between hospital settings. Overall the manuscript makes a useful contribution on an important topic. Addressing the comments above would further improve it. I hope these suggestions are helpful for the authors. Please feel free to let me know if you need any clarification or have additional questions!

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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: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Attachments

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Submitted filename: Referee_answer.pdf

Attachment

Submitted filename: review PONE-D-23-31373.docx

PONE-D-23-31373R1Frequency and mortality rate following antimicrobial-resistant bloodstream infections in tertiary-care hospitals compared with secondary-care hospitalsPLOS ONE

Dear Dr. Limmathurotsakul,

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 Apr 27 2024 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,

Ali Amanati

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:

Dear authors

We are pleased to inform you that your manuscript has passed through ‎‎the ‎review stage and is ready for revision. The manuscript's overall ‎‎presentation ‎improved after amendments; ‎‎however, ‎still needs minor revision.‎

Editor comments:

Abstract:‎

‎Add corresponding statistics in the “results” section for the data presented in ‎the abstract section. Address the following shortcomings: ‎

a. “The frequencies of hospital-origin AMR BSI per 100,000 patient-days at risk ‎in TCHs were about twice that in SCHs for most pathogens under evaluation.”; ‎add frequencies and p. value. ‎

b. “All-cause in-hospital mortality (%) following hospital-origin AMR BSI was

not significantly different between TCHs and SCHs.”; add p. value.‎

c. “However, due to the higher frequencies, all-cause in-hospital mortality rates ‎following hospital-origin AMR BSI per 100,000 patient-days at risk were ‎considerably higher in TCHs for most pathogens.”; remove “However”; add ‎frequencies and p. value.‎

d. the following statement need corrections: ‎

‎“For example, the all-cause in-hospital mortality rate ...”; remove “For example, ”‎

e. Conclusion should be improved (both abstract and main text). It is a fact that AMR is varied in different ‎hospital settings. Based on the results of your study, you should highlight the ‎important indicators that found to be clinically more different and suggest ‎appropriate action to address issues.‎

[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: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: 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 #3: Yes

Reviewer #4: Yes

**********

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

Reviewer #1: No

Reviewer #3: Yes

Reviewer #4: 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 #3: Yes

Reviewer #4: 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 #3: Yes

Reviewer #4: 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: Your statistical section leaves me feeling disconnected for a couple of reasons. Firstly, there's no mention of demographic variables for the patients. Was this data unavailable or deemed unnecessary for your model? Secondly, the confounding variables you adjusted for aren't specified. Were these variables shared between patients and hospitals? Were they chosen based on their relevance to patients or hospitals? The only insights provided are tucked away in the supplementary file, in the footer of the tables.

Reviewer #3: No further comments at this stage. Authors have tried to address largely the concerns raised earlier.

Reviewer #4: All the previous comments have been addressed but the author have not mentioned which AMR proportions and Mortalities were analyzed using either the chi square test or fisher exact test or both.

line 222: author repeatedly mentioned "estimate of magnitude" but there is no mention of coefficient in result section , figures or in the supplemental material. kindly provide the output of analysis in stata showing coefficient.

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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 #3: No

Reviewer #4: 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.

PONE-D-23-31373R2Frequency and mortality rate following antimicrobial-resistant bloodstream infections in tertiary-care hospitals compared with secondary-care hospitalsPLOS ONE

Dear Dr. Limmathurotsakul,

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 May 23 2024 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,

Ali Amanati

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:

Dear authors,

New comments were posted by the reviewer #1. So, the manuscripts require a round of revision.‎ Please provide a point-by-point response to the reviewer comments and highlight all the ‎amends on your manuscript with yellow color.‎

Yours

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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: (No Response)

Reviewer #4: 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 #4: Yes

**********

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

Reviewer #1: No

Reviewer #4: 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 #4: 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 #4: Yes

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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: I appreciate the research team for answering the concerns. The authors' response does address some of the concerns by providing clarification on the nature of the data and the purpose of the study. However, there are still aspects that could be further explicit to improve the clarity and robustness of the study.

Demographic Variables: The authors clarify that individual patient-level data on demographic variables was not collected and that the study relied on aggregated statistics. While this explanation addresses the absence of demographic variables, it would be beneficial for the authors to explain why such data was not collected or why it was not deemed necessary for the model.

Confounding Variables: The authors mention that multivariable mixed-effect models were performed to control for other variables, including blood culture utilization rates of the hospitals and the health region where the hospitals were located. While this adds some clarity regarding the confounding variables, it would be helpful for the authors to elaborate on why these specific variables were chosen and how they were determined to be relevant to the analysis. Additionally, providing information on any other potential confounders that were considered but not included in the analysis would strengthen the robustness of the study.

Reviewer #4: no Comments . all the previous comments have been addressed .

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Reviewer #1: No

Reviewer #4: No

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Frequency and mortality rate following antimicrobial-resistant bloodstream infections in tertiary-care hospitals compared with secondary-care hospitals

PONE-D-23-31373R3

Dear Dr. Direk Limmathurotsakul,

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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Ali Amanati

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I read the revised manuscript ‎

I have no further comments to add. I thank the authors for their detailed ‎‎replies to the reviewers' comments.‎

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

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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

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

Reviewer #1: Yes

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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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Reviewer #1: Yes

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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)

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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

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