Adopting a model of antimicrobial stewardship program to anti-tubercular treatment stewardship: A single-centre experience from a private tertiary care hospital in South India

Swathy S. Samban; Akhilesh Kunoor; Preetha Prasanna; Malavika Krishnakumar; Nandita Shashindran; Chithira V. Nair; Abhinandh Babu; Ananth Ram K. J.; Sivapriya G. Nair; Subhash Chandra; Kiran G. Kulirankal; Georg Gutjahr; Rakesh P. S.; Dipu T. Sathyapalan; Merlin Moni

doi:10.1371/journal.pone.0310493

Peer Review History

Original SubmissionJune 18, 2024
16 Jul 2024 Decision Letter - Arghya Das, Editor PONE-D-24-23210Adopting a Model of Antimicrobial Stewardship Program to Anti-Tubercular Therapy Stewardship: A Single-CentreExperience from a Private Tertiary Care Hospital in South IndiaPLOS ONE Dear Dr. T Sathyapalan, 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 Aug 30 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, Arghya Das, MD Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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 additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (a) whether consent was informed and (b) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. 3. 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: Authors of the present manuscript presents a proof of concept for antimicrobial stewardship in tuberculosis which they have mentioned as Anti-Tubercular Therapy Stewardship (ATTSP). From the same institute, a previously published article mentioned the term "anti-tuberculosis treatment stewardship". As a new concept is being presented, it is advisable if the authors could use uniform terminologies to describe the concept. Although the concept presented in the manuscript is new and pertinent in contemporary landscape of TB treatment (with special emphasis to private sector hospitals), it appears to be more of a prescription audit. The exclusion of one of the 5Rs 'Right Duration' from the assessment is justifiable due to lack of follow up data after discharge, consideration of few important aspects like monitoring adverse drug reactions during inpatient treatment could make the study more meaningful. Please address the above in the revised version of the manuscript under DISCUSSION. MATERIALS AND METHODS Line 101: This prospective cohort study was conducted................. Comment: The study design does not seem to be that of a prospective cohort study. Please mention it as a descriptive observational study only. Line 114: ...........Centres for Disease Control and Prevention (CDC) Comment: Please mention the above as United States CDC Line 143: Fig 2: Extrapolating the benefits of implementing ATT across the private hospitals in India Comment: Figure 2 and its legends have been mentioned twice in the manuscript; once under MATERIALS AND METHODS and second time under DISCUSSION Line 156-158: New cases/recurrence/ relapse..................................National Tuberculosis Elimination Programme (NTEP) Comment: Please cite the suitable reference for the above sentence. RESULTS Lines 184-185: ..................no recommendations were filed as three patients were discharged early. Comment: It is not understood why recommendations could not be filed for three patients who were discharged. In the event of detection of inappropriate prescription, it's a sine qua non to rectify the same to avoid further complications. Please explain. Lines 193-196: The most common recommendation was optimising the ATT dose. Among the 27 recommendations filed for dose adjustment, 15 were for inappropriately high doses and 12 for inappropriately low doses. Comment: The above statistics require more elaboration. Was there any effect of age-group (like children) on the high doses or low doses? That means, whether the wrong prescribed doses may be resulting from not-considering dose-adjustments or wrongly calculating the doses. If such instances are documented please include them in the revised manuscript. In the same context, it is also advisable to add the demographic details, drugs prescribed including the inappropriate ones and inappropriate doses prescribed, inappropriate frequency and inappropriate indication in a tabular format for those 36 cases where recommendations were filed. Please upload this information as a Supplementary file. Lines 237-239: ...................so an information-technology-enabled platform for providing................................associations or city consortiums of private providers may be developed. Comment: One such IT-based platform ERS/WHO TB Consilium to provide rapid advice to clinicians already exists. Please consider adding it under the same paragraph adding suitable references. TABLE 1: Tables should be self explanatory. Please expand all abbreviations in the footnote. FIGURES: All figures should also be cited sequentially in the text. Figure 2 seems to be reproduced from other sources. Please acknowledge the source and cite the reference accordingly. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 ****** 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 ****** 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: As TB is increasing burden in our country , we have to strengthen the treatment by implementing ATTSP. Drug therapy for TB take longer duration, so we need to titrate the treatment course well organised without have any misdirections. Proper drug therapy will enhance the treatment outcome. Reviewer #2: its a novel concept especially for developing countries where rampant use of ATT drugs has happened leading to surge in MDR and XDR cases of TB. The article is well written and easy to understand. The workflow can be implemented at other places too. ****** 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: Dr M R Vasanthapriyan Reviewer #2: Yes: Dr VIKRAMJEET SINGH, MD, DNB Microbiology, Assistant Professor, SGPGI Lucknow ******** [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.0310493.r001
Revision 1
29 Aug 2024 Author Response Dear Reviewer’s, We sincerely thank you for the time and effort you have invested in reviewing our manuscript. We are grateful for your constructive feedback, which has helped us enhance the quality and clarity of our work. We have carefully addressed each of the points raised in your review and have made the necessary revisions to the manuscript. We have provided detailed responses to each comment, and added supplementary materials where appropriate. Additionally, we have updated the author list to include Dr. Binny P. Prabhu and Dr. Nandita Shashindran acknowledging their significant contributions to the study. We trust that these revisions meet your expectations and contribute to the overall improvement of our manuscript. We look forward to your further insights. Thank you once again for your valuable feedback. Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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 Carefully reviewed and formatted the manuscript according to the PLOS ONE's style requirements 2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (a) whether consent was informed and (b) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. ANS: Thank you for your comments. In our study, written informed consent was obtained from all participants. For the nine paediatric participants included in the study, written consent was duly obtained from their parents or legal guardians. This has been clarified in the Methods section under the heading Patient Consent Statement. We will also ensure that this information is appropriately reflected in the online submission details. Line numbering: 117 - 120 This study was not a retrospective study. Informed written consent was obtained from all participants prospectively, prior to data collection. 3. 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. ANS: Thank you for the careful review of the manuscript and insightful comments. The reference list as requested was reviewed and confirmed that none of the cited papers have been retracted. To enhance the manuscript, additional reference has been added that is highly relevant to the topic discussed: Singh S, Menon VP, Mohamed ZU, Kumar VA, Nampoothiri V, Sudhir S, Moni M, Dipu TS, Dutt A, Edathadathil F, Keerthivasan G. Implementation and impact of an antimicrobial stewardship program at a tertiary care center in South India. In Open Forum Infectious Diseases 2019 Apr (Vol. 6, No. 4, p. ofy290). US: Oxford University Press. This reference is particularly important as it details antimicrobial stewardship model implemented at the same institution, providing a comprehensive context and supporting the findings presented in the manuscript. All changes to the reference list have been reflected in the revised manuscript, as reference number 25. Additional Editor Comments: 1. A) Authors of the present manuscript presents a proof of concept for antimicrobial stewardship in tuberculosis which they have mentioned as Anti-Tubercular Therapy Stewardship (ATTSP). From the same institute, a previously published article mentioned the term "anti-tuberculosis treatment stewardship". As a new concept is being presented, it is advisable if the authors could use uniform terminologies to describe the concept. ANS 1.A) Thank you for your valuable feedback. We understand the importance of using uniform terminologies to describe the concept. In light of your suggestion, we have revised the terminology in our manuscript to "anti-tubercular treatment stewardship program (ATTSP)" to ensure consistency with previous publications from our institute, along with the fact that ATT is expanded as “Anti Tubercular Treatment” in RNTCP guidelines. We believe this will help maintain clarity and uniformity in the literature. B) Although the concept presented in the manuscript is new and pertinent in contemporary landscape of TB treatment (with special emphasis to private sector hospitals), it appears to be more of a prescription audit. ANS 1.B) Thank you for your feedback. While we understand that the concept may appear similar to a prescription audit, it is more accurately described as a stewardship model that was adopted. Specifically, it represents the widely accepted stewardship strategy of prospective audit and feedback. This approach includes a prospective audit and feedback mechanism, along with tracking compliance, which distinguishes it from a simple prescription audit. To ensure clarity, we have now added the explanation of this strategy to the discussion section of the manuscript. Line numbering 253-256. C)The exclusion of one of the 5Rs 'Right Duration' from the assessment is justifiable due to lack of follow up data after discharge, ANS 1.C) The exclusion of the 'Right Duration' from our assessment is indeed due to the lack of follow-up data post-discharge, as mentioned. We have already acknowledged this in the limitations section under the discussion section of the manuscript. Line numbering.310-311 D) Consideration of few important aspects like monitoring adverse drug reactions during inpatient treatment could make the study more meaningful. Please address the above in the revised version of the manuscript under DISCUSSION. ANS 1.D) Thank you for your insightful suggestion regarding the inclusion of adverse drug reaction (ADR) monitoring. We have now addressed this in the revised manuscript. This information has been incorporated into both the results and discussion sections and has also been added as supporting information (S1 Table). Line numbering 228-230, 261-262 2. MATERIALS AND METHODS Line 101: This prospective cohort study was conducted................. Comment: The study design does not seem to be that of a prospective cohort study. Please mention it as a descriptive observational study only. ANS 2: Thank you for the comment. We agree that the study design is more accurately described as an observational study. To reflect this, we have revised the manuscript to describe the study as a “prospective observational study”. Line numbering: 110,243 3. Line 114: ...........Centres for Disease Control and Prevention (CDC) Comment: Please mention the above as United States CDC ANS 3: Thank you for your suggestion. We have revised the manuscript to specify "United States CDC" as requested. Line numbering: 129 4. Line 143: Fig 2: Extrapolating the benefits of implementing ATT across the private hospitals in India Comment: Figure 2 and its legends have been mentioned twice in the manuscript; once under MATERIALS AND METHODS and second time under DISCUSSION ANS: Thank you for bringing this to our attention. We will revise the manuscript to ensure Figure 2 and its legends are mentioned only once, under the DISCUSSION section. 5. Line 156-158: New cases/recurrence/ relapse..................................National Tuberculosis Elimination Programme (NTEP) Comment: Please cite the suitable reference for the above sentence. ANS: Thank you for pointing out the need for citation. Appropriate reference added to support the statement regarding new cases, recurrence, and relapse in the context of the National Tuberculosis Elimination Programme (NTEP). Ref number 28. 6. RESULTS Lines 184-185: ..................no recommendations were filed as three patients were discharged early. Comment: It is not understood why recommendations could not be filed for three patients who were discharged. In the event of detection of inappropriate prescription, it's a sine qua non to rectify the same to avoid further complications. Please explain. ANS: Thank you for your comment. The filing of recommendations refers to documenting them directly in the patients' files, a process primarily conducted for inpatients. For the three patients who were discharged early, direct filing was not feasible. However, in these instances, the clinicians were promptly informed of the recommendations either in person or over the phone. This clarification has been addressed in the results section of the manuscript. Line numbering: 211-213 7. Lines 193-196: The most common recommendation was optimising the ATT dose. Among the 27 recommendations filed for dose adjustment, 15 were for inappropriately high doses and 12 for inappropriately low doses. Comment: The above statistics require more elaboration. Was there any effect of age-group (like children) on the high doses or low doses? That means, whether the wrong prescribed doses may be resulting from not-considering dose-adjustments or wrongly calculating the doses. If such instances are documented please include them in the revised manuscript. In the same context, it is also advisable to add the demographic details, drugs prescribed including the inappropriate ones and inappropriate doses prescribed, inappropriate frequency and inappropriate indication in a tabular format for those 36 cases where recommendations were filed. Please upload this information as a Supplementary file. ANS: Effect of Age-Group on Dose Errors: In our analysis we observed that an increase in age was associated with a higher likelihood of dosing errors. This analysis has been detailed in the supporting information (S2 Table). Line numbering: 231-232 Causes of Incorrect Dosing: The majority of dosing errors were attributed to incorrect dose calculations. Specific issues included doses exceeding the maximum recommended dose and instances of underdosing even in scenarios where patients show mildly deranged liver enzymes. Additionally, there were cases where frequency of administration of drug were not considered in patients with chronic kidney disease (CKD). This is now included in the discussion section. Line numbering. Line numbering:263-267 We have added a supplementary table providing detailed demographic information, including the drugs prescribed (both appropriate and inappropriate), inappropriate doses, frequencies, and indications for the 36 cases where recommendations were filed. This table is now included as supplementary material to offer a comprehensive view of the dosing issues encountered. Added as supporting information (S3 Table). 8. Lines 237-239: ...................so an information-technology-enabled platform for providing................................associations or city consortiums of private providers may be developed. Comment: One such IT-based platform ERS/WHO TB Consilium to provide rapid advice to clinicians already exists. Please consider adding it under the same paragraph adding suitable references. ANS: Thank you for your valuable suggestion. We have incorporated it to the manuscript with suitable reference. Line numbering: 283-287. Reference number:30 9. TABLE 1: Tables should be self explanatory. Please expand all abbreviations in the footnote. Thank you for the suggestion. The abbreviations in Table 1 have been expanded in the footnote to ensure the table is self-explanatory. 10. FIGURES: All figures should also be cited sequentially in the text. Figure 2 seems to be reproduced from other sources. Please acknowledge the source and cite the reference accordingly. ANS: Thank you for your feedback. The figures have been cited sequentially in the text. For Figure 2, the statistics used for extrapolation were taken from the National Strategic Plan, mentioned accordingly in the manuscript and the figure itself is an original creation. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0310493.r002
2 Sep 2024 Decision Letter - Arghya Das, Editor Adopting a model of antimicrobial stewardship program to anti-tubercular treatment stewardship: A single-centreexperience from a private tertiary care hospital in South India PONE-D-24-23210R1 Dear Dr. T Sathyapalan, 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, Arghya Das, MD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0310493.r003
Formally Accepted
16 Oct 2024 Acceptance Letter - Arghya Das, Editor PONE-D-24-23210R1 PLOS ONE Dear Dr. Sathyapalan, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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 Dr. Arghya Das Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0310493.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .