Risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections in Shanghai: A five-year retrospective cohort study

Hongwen Cao; Siqi Zhou; Xuefeng Wang; Shuzhen Xiao; Shengyuan Zhao

doi:10.1371/journal.pone.0324925

Peer Review History

Original SubmissionDecember 31, 2024
31 Dec 2024 Author Response https://doi.org/10.1371/journal.pone.0324925.r001
11 Feb 2025 Decision Letter - Ali Amanati, Editor PONE-D-24-58014Risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections in Shanghai: a five-year retrospective cohort studyPLOS ONE Dear Dr. Zhao, 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 Mar 28 2025 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: 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. In the online submission form, you indicated that [Some of relevant data are within the manuscript and its Supporting Information files. All the datasets used and/or analyzed during the current study are also available from the corresponding authors on reasonable request.]. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Additional Editor Comments: Editor’s comments Your manuscript [PONE-D-24-58014] has passed the review stage and is ready for ‎revision. ‎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.‎ Technical points:‎ ‎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 a yellow color ‎3. Use line numbering and page number in the next submission‎ The Editor’s main concern:‎ Why wasn't there an investigation into the risk factors for mortality in Klebsiella pneumoniae bloodstream infections? The study effectively explores CRKP and MDR KP. However, incorporating a discussion of risk scoring systems like the Increment CPE Score could strengthen the paper by providing a framework for predicting and understanding mortality risk in these infections. I recommend the authors consider adding this to the discussion. [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 Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ****** 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 ****** 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: No Reviewer #2: No Reviewer #3: Yes Reviewer #4: 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: I appreciate the opportunity to evaluate this manuscript. It provides valuable insights into the risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections, and I have a few comments and suggestions that may help enhance its clarity and impact. The introduction contains several long sentences that could be broken down for better readability. For example, the sentence "Moreover, KP BSIs resulted in high mortality rates ranged between 20% and 40%, which has attracted attention" could be split into two sentences for clarity. The terms "MDRKP" and "CRKP" are introduced without prior definitions in the background section. The phrase "the resistance situation has become more serious in recent years" is somewhat redundant, as it implies a known trend without providing specific evidence. The sentence "Only the first episode of each patient was included and only one episode per patient was included" is redundant. It can be simplify to: "Only the first episode of KP BSI per patient was included." The phrasing "Definition of each variable corresponding to these data was listed in Appendix Table 1" is vague and should be made clearer. It can be stated as "Definitions of the variables collected are provided in Appendix Table 1." The phrase "Because of the retrospective nature of the study, the committee waived informed consent" may lead to misinterpretation and could benefit from further clarification. The discussion around ICU admissions is well-articulated, linking it to the increased prevalence of MDRKP and CRKP BSIs. However, it would strengthen the argument to include references or data that support the assertion that ICUs "generate, spread, and amplify antimicrobial resistance." Citing specific studies or statistics could bolster this claim. The identification of respiratory and genitourinary diseases as independent risk factors is significant. Consider discussing the biological plausibility behind these associations in more detail, perhaps by referencing studies that have explored the mechanisms linking these conditions to increased susceptibility to infections. To enhance the clarity and readability of your paper, I recommend avoiding nested parentheses (lines 96-97 and line 103). In line 120, you mentioned the ratio of ratios (OR). It should be referred to as the Odds Ratio. Have you used a generalized linear mixed model or a generalized linear model? (Line 110). How did you assess the goodness of fit of the logistic regression model? Multiple logistic regression is the more appropriate term than multivariate logistic regression. Reviewer #2: Dear Authors Thank for you the write-up. Kindly address the following concerns General concerns If patients with less than 48 hours of admission were excluded, then the title and focus of the study should reflect Hospital-acquired Klebsiella blood stream infections in order to properly align with the exclusion criteria otherwise, a clear and scientifically justifiable explanation should be given for the referenced exclusion criterion The conclusion sounds too sentimental and would be better rephrased specific concerns Abstract should contain at least a statement of reflecting background before jumping to objectives An abbreviation “CR” was introduced in the abstract which had not been previously explained Line 51, readers will appreciate better if ‘good’ or ‘bad’ is used to properly qualify the ‘prognosis’ in the text. Line 54% - please clarify is it proportion among all blood culture isolates or among Klebsiella isolates? Line 57 – the import of the statement is not well articulated and difficult to understand Line 120, kindly correct, ‘ratio of ratios’ Reviewer #3: Compared with some prior submissions, the writing in this article is exceptionally good. I read through it enough to get the sense that a fairly good writer composed this work, compared with the struggles one sometimes sees in articles that have to undergo repeated rewrites. This is a very useful topic in need of review across each health care system, and region with its own unique epidemiological, demographic and climatic-meteorologic-ecological settings. Long term studies focused on bacteriological phenotypic changes regarding MDRKP and CRKP treatment are most important, and very long term studies of changes in frequencies over time for a patter of ten to twenty years certain provides us with very important insights into the evolutionary process of pathogens and the development of drug resistance. This article is certain succinct enough for me with regard to how it reports the overall findings. Some individuals might be a little too detail oriented with figure 2, but that alone is not enough to really demand much of a change in the three (2 + 1) color patterns theoretically expressed due to the minor differences in figure A (ALL) versus the remaining two (a Cardiothoracic Surgery vs Pancreatic Surgery vs Burn Unit color mismatch.). This may very well be due to the printing of these figures and software issues, but I do not necessarily require that somehow this be fully and completely dealt with. In theory, such a correction or change should be quite easy to render in the submission of a final draft for publication. This change is requested, even suggested, but is not required. Reviewer #4: Review Comments to the Author The study is well-designed and addresses an important topic with significant clinical relevance, especially in regions with high levels of antimicrobial resistance. The statistical analysis is thorough, and the conclusions are well-supported by the data. The manuscript is written in clear English, and the figures and tables effectively illustrate the findings. However, the following recommendations are suggested to enhance the paper: 1. A more detailed discussion of the limitations is crucial for improving transparency and providing a clearer framework for future research. 2. Expanding on the implications for clinical interventions and public health policies would significantly increase the practical impact of the findings. 3. Additionally, the descriptive captions for figures and tables should be improved to ensure they are clear and easily understandable on their own. 4. The author should specify the name of the electronic medical record system used. ****** 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: Yes: Farzane Ahmadi Reviewer #2: No Reviewer #3: Yes: Brian L Altonen 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. https://doi.org/10.1371/journal.pone.0324925.r002
Revision 1
12 Mar 2025 Author Response Dear Editor, We have submitted the manuscript entitled “Risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections in Shanghai: a five-year retrospective cohort study” to PLOS ONE (manuscript ID: PONE-D-24-58014). Now we submitted a revised version of this manuscript, in which each point raised by editor and the reviewers has been addressed and all the changes have been highlighted in yellow throughout the manuscript. We deeply appreciate the valuable comments and suggestions. Why wasn't there an investigation into the risk factors for mortality in Klebsiella pneumoniae bloodstream infections? The study effectively explores CRKP and MDR KP. However, incorporating a discussion of risk scoring systems like the Increment CPE Score could strengthen the paper by providing a framework for predicting and understanding mortality risk in these infections. I recommend the authors consider adding this to the discussion. Response: Thank you for your advice. Actually we have investigated risk factors for crude 30-day mortality of Klebsiella pneumoniae bloodstream infections (KP BSIs) using the same dataset of this manuscript and published the findings in 2024, please see reference 5 (https://doi.org/10.1080/23744235.2024.2374980). We found that MDR/CR phenotypes were associated with increased mortality of KP BSIs and healthcare costs (reference 5 and lines 50-55) and CR phenotype was one of independent risk factors for crude 30-day mortality of KP BSIs (reference 5). Therefore, we focused on exploring risk factors for MDRKP and CRKP BSIs in this manuscript. Although we reported in-hospital mortality rate in the current study, given that we have published the work on risk factors for crude 30-day mortality of KPBSIs using the same dataset, we did not look any further into risk factors for in-hospital mortality of KPBSIs in this study. Thank you very much for your kind support and consideration of our manuscript. Kind regards, Shengyuan Dear reviewers, Thank you very much for your valuable comments and suggestions. We have responded to each of your comments and questions and revised the manuscript accordingly. We highlighted all the revisions throughout the manuscript in yellow. Please see our responses in the below. Reviewer #1: I appreciate the opportunity to evaluate this manuscript. It provides valuable insights into the risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections, and I have a few comments and suggestions that may help enhance its clarity and impact. The introduction contains several long sentences that could be broken down for better readability. For example, the sentence "Moreover, KP BSIs resulted in high mortality rates ranged between 20% and 40%, which has attracted attention" could be split into two sentences for clarity. Response: Thank you for your advice. We have double checked the background section and broken down several long sentences as suggested. Please see lines 41-42, 44-47, 50-55. The terms "MDRKP" and "CRKP" are introduced without prior definitions in the background section. Response: Apologies. We have added the definitions of “MDRKP” and “CRKP” as suggested. Please see lines 51-52. The phrase "the resistance situation has become more serious in recent years" is somewhat redundant, as it implies a known trend without providing specific evidence. Response: Apologies. You are right. We have deleted the phrase to make the sentence clear and meaningful. Please see lines 57-58. The sentence "Only the first episode of each patient was included and only one episode per patient was included" is redundant. It can be simplify to: "Only the first episode of KP BSI per patient was included." Response: Thank you for your advice. We have simplified the sentence as suggested to “Only the first episode of KP BSIs per patient was included.”, please see line 73. The phrasing "Definition of each variable corresponding to these data was listed in Appendix Table 1" is vague and should be made clearer. It can be stated as "Definitions of the variables collected are provided in Appendix Table 1." Response: Apologies. To make it clearer, we have rewritten the sentence as “Definitions of the variables collected are provided in S1 Table.” as suggested, please see lines 99-100. The phrase "Because of the retrospective nature of the study, the committee waived informed consent" may lead to misinterpretation and could benefit from further clarification. Response: Apologies. We have rewritten the sentence as “This is an observational retrospective study and all the data were obtained from medical record systems and analyzed anonymously, so the committee waived informed consent.” to make it clearer. Please see lines 79-81. The discussion around ICU admissions is well-articulated, linking it to the increased prevalence of MDRKP and CRKP BSIs. However, it would strengthen the argument to include references or data that support the assertion that ICUs "generate, spread, and amplify antimicrobial resistance." Citing specific studies or statistics could bolster this claim. Response: Thank you for your advice. We have added more supporting information and references as suggested, please see lines 202-206. The identification of respiratory and genitourinary diseases as independent risk factors is significant. Consider discussing the biological plausibility behind these associations in more detail, perhaps by referencing studies that have explored the mechanisms linking these conditions to increased susceptibility to infections. Response: Thank you for your advice. We have added more discussion and references as suggested, please see lines 227-236. To enhance the clarity and readability of your paper, I recommend avoiding nested parentheses (lines 96-97 and line 103). Response: Apologies. We have deleted unnecessary expressions to avoid nested parentheses as suggested, please see lines 96-98 and 104-105. In line 120, you mentioned the ratio of ratios (OR). It should be referred to as the Odds Ratio. Response: Apologies. We have corrected this mistake as suggested. Please see line 121. Have you used a generalized linear mixed model or a generalized linear model? (Line 110). Response: Apologies. We used a generalized linear model, and we have corrected this, please see line 111. How did you assess the goodness of fit of the logistic regression model? Response: Hosmer-Lemeshow test was performed to assess the goodness of fit of the logistic regression models. We have added this in the methods section (lines 125-126) and reported the results in results section (lines 170-171 and 176-177). Multiple logistic regression is the more appropriate term than multivariate logistic regression. Response: Thank you for your advice. We have changed to multiple logistic regression throughout the manuscript as suggested. Reviewer #2: Dear Authors Thank for you the write-up. Kindly address the following concerns General concerns If patients with less than 48 hours of admission were excluded, then the title and focus of the study should reflect Hospital-acquired Klebsiella blood stream infections in order to properly align with the exclusion criteria otherwise, a clear and scientifically justifiable explanation should be given for the referenced exclusion criterion Response: In this study, the inclusion criteria for patients was primarily based on the results of blood cultures. Inpatients with at least one result of Klebsiella pneumoniae in blood culture were included in our study. According to the Centres for Disease Control and Prevention’s criteria, hospital-associated bloodstream infection (BSI) was defined as a BSI that occurred more than 48 hours after admission to hospital or within 48 hours of the last hospital discharge (doi:10.1016/j.ajic. 2008.03.002). For inpatients with more than 48 hours hospitalization but whose bloodstream infection occurred within 48 hours of hospital admission, we did not exclude them. In this study, there was one patient with schizophrenia who did not take the right amount of medicines on time as the physician suggested and was transferred to a psychiatric hospital for treatment 32 hours after hospital admission. This patient took the first positive blood culture of Klebsiella pneumoniae 20 hours after hospital admission. We could not know the exact amount of medicines the patient took by checking medical records. Therefore, we excluded this patient due to inaccurate medical records. There was one elder patient with advanced malignancy who was suggested to be admitted to ICU at admission given that the illness was very severe and the clinical prognosis would be quite poor without life support equipment. Both the patient and families refused to be transferred to ICU and insisted on discharge because they could not afford the healthcare costs for treatment. This patient took the first positive blood culture of Klebsiella pneumoniae at hospital admission. Therefore, we excluded this patient. The two patients mentioned above excluded from this study happened to be with less than 48 hours of hospitalization. As you suggested, the expression of “patients with less than 48 hours of hospitalization were excluded” is misleading, so we have rewritten the exclusion criteria to make it clearly justified as suggested, please see lines 75-76. The conclusion sounds too sentimental and would be better rephrased Response: Thank you for your advice. We have rephrased the conclusion section as suggested, please see lines 35-39 and 286-293. specific concerns Abstract should contain at least a statement of reflecting background before jumping to objectives Response: Thank you for your advice. We have added the background statement as suggested, please see lines 19-21. An abbreviation “CR” was introduced in the abstract which had not been previously explained Response: Apologies. CR means CRKP BSIs, we have rewritten the sentence to make it clearer. Please see line 29. Line 51, readers will appreciate better if ‘good’ or ‘bad’ is used to properly qualify the ‘prognosis’ in the text. Response: Apologies. It should be bad prognosis. We have added the word to make it clear as suggested. Please see line 50. Line 54 - please clarify is it proportion among all blood culture isolates or among Klebsiella isolates? Response: Apologies. The proportion is among Klebsiella pneumoniae isolates. We have clarified this as suggested, please see line 54. Line 57 – the import of the statement is not well articulated and difficult to understand Response: Apologies. The phrase is somewhat redundant as it implies a known trend and not clear. We have rephrased the sentence to make it clear and meaningful. Please see lines 57-58. Line 120, kindly correct, ‘ratio of ratios’ Response: Apologies. We have corrected this mistake as suggested. Please see line 121. Reviewer #3: Compared with some prior submissions, the writing in this article is exceptionally good. I read through it enough to get the sense that a fairly good writer composed this work, compared with the struggles one sometimes sees in articles that have to undergo repeated rewrites. This is a very useful topic in need of review across each health care system, and region with its own unique epidemiological, demographic and climatic-meteorologic-ecological settings. Long term studies focused on bacteriological phenotypic changes regarding MDRKP and CRKP treatment are most important, and very long term studies of changes in frequencies over time for a patter of ten to twenty years certain provides us with very important insights into the evolutionary process of pathogens and the development of drug resistance. This article is certain succinct enough for me with regard to how it reports the overall findings. Some individuals might be a little too detail oriented with figure 2, but that alone is not enough to really demand much of a change in the three (2 + 1) color patterns theoretically expressed due to the minor differences in figure A (ALL) versus the remaining two (a Cardiothoracic Surgery vs Pancreatic Surgery vs Burn Unit color mismatch.). This may very well be due to the printing of these figures and software issues, but I do not necessarily require that somehow this be fully and completely dealt with. In theory, such a correction or change should be quite easy to render in the submission of a final draft for publication. This change is requested, even suggested, but is not required. Response: Apologies. We have corrected the colors of Figure 2 to make sure that the colors match departments among the three groups as suggested. Reviewer #4: Review Comments to the Author The study is well-designed and addresses an important topic with significant clinical relevance, especially in regions with high levels of antimicrobial resistance. The statistical analysis is thorough, and the conclusions are well-supported by the data. The manuscript is written in clear English, and the figures and tables effectively illustrate the findings. However, the following recommendations are suggested to enhance the paper: 1. A more detailed discussion of the limitations is crucial for improving transparency and providing a clearer framework for future research. Response: Thank you for your advice. We have added more detailed information about limitations in the discussion section as suggested, please see lines 264-275. 2. Expanding on the implications for clinical interventions and public health policies would significantly increase the practical impact of the findings. Response: Thank you for your advice. We have added more discussion on the implications for clinical interventions and public health policies as suggested, please see lines 276-283. 3. Additionally, the descriptive captions for figures and tables should be improved to ensure they are clear and easily understandable on their own. Response: Apologies. We have rephrased the descriptive captions for figures and tables to make them clear and easily understandable on their own as suggested. 4. The author should specify the name of the electronic medical record system used. Response: Apologies. We have specified this as suggested, please see lines 65-67. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0324925.r003
24 Apr 2025 Decision Letter - Ali Amanati, Editor PONE-D-24-58014R1Risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections in Shanghai: a five-year retrospective cohort studyPLOS ONE Dear Dr. Zhao, 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 Jun 08 2025 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 successfully passed the ‎review stage and is ready for revision. Although the overall presentation of the ‎manuscript has improved following amendments, it still requires further ‎revision.‎ Yours sincerely,‎ [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 Reviewer #2: 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 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: Yes Reviewer #2: No ****** 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: (No Response) ****** 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: Dear authors, Thank you for addressing all the comments in your manuscript. I have no further comments to add. Reviewer #2: Dear authors If the data set for this write-up has been used in previous publication (s), in order to conform to ethical standards, this must be clearly stated in the methodology section and the new or entirely different research question this write-up seeks to address unambiguously stated as well. ****** 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: Yes: Farzane Ahmadi 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. https://doi.org/10.1371/journal.pone.0324925.r004
Revision 2
1 May 2025 Author Response Dear reviewer, Thank you very much for your valuable comments and suggestions. We have responded to your comment and revised the manuscript accordingly. We highlighted all the revisions throughout the manuscript in yellow. Please see our responses in the below. If the data set for this write-up has been used in previous publication (s), in order to conform to ethical standards, this must be clearly stated in the methodology section and the new or entirely different research question this write-up seeks to address unambiguously stated as well. Response: Thank you. We have added the statement “We investigated incidence, antimicrobial resistance, crude 30-day mortality rate, and risk factors for crude 30-day mortality of KP BSIs using the same dataset of this manuscript (S1 File) and published the findings in 2024 [5]. In this study, we investigated temporal distribution of proportion of KP BSIs attributed deaths, department distribution of KP BSIs and risk factors for MDRKP BSIs and CRKP BSIs which are entirely different research questions. There is no overlap in research content of the two studies.” in the methodology section as suggested, please see lines 82-88. Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_2.docx https://doi.org/10.1371/journal.pone.0324925.r005
4 May 2025 Decision Letter - Ali Amanati, Editor Risk factors for multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae bloodstream infections in Shanghai: a five-year retrospective cohort study PONE-D-24-58014R2 *Dear Dr. Shengyuan Zhao,* 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Ali Amanati Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have managed to use all the available resources and data to re-shape ‎the manuscript in a manner that is more scientifically sound than previously.‎ https://doi.org/10.1371/journal.pone.0324925.r006
Formally Accepted
Acceptance Letter - Ali Amanati, Editor PONE-D-24-58014R2 PLOS ONE Dear Dr. Zhao, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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 customercare@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 Professor Ali Amanati Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0324925.r007

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