Resistance pattern of infected chronic wound isolates and factors associated with bacterial resistance to third generation cephalosporins at Mbarara Regional Referral Hospital, Uganda

Wangoye Khalim; James Mwesigye; Martin Tungotyo; Silvano Samba Twinomujuni

doi:10.1371/journal.pone.0261264

Peer Review History

Original SubmissionJuly 6, 2021
26 Oct 2021 Decision Letter - Grzegorz Woźniakowski, Editor PONE-D-21-22072 Resistance pattern of infected chronic wound isolates and factors associated with bacterial resistance to third generation cephalosporins at Mbarara Regional Referral Hospital, Uganda. PLOS ONE Dear Dr. Khalim, 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 Nov 20 2021 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. 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If you have no competing interests, please state ""The authors have declared that no competing interests exist."", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now This information should be included in your cover letter; we will change the online submission form on your behalf. 4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. 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 (if provided): [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Overall this was a good study that focused on a matter of great public health importance. While the study objectives are listed in the abstract there is no mention of the objectives in the methodology sections. It is not clear whether the authors differentiated between hospital or community acquired chronic wound infections given that this may influence antibiotic resistance patterns. While there was a consideration for ≤2 prior hospitalizations it is not clear whether “0” or no hospitalization was also evaluated. While the background section mentions some comorbidities as factors contributing to bacterial resistance the authors do not state what comorbidities the study participants were evaluated for. Despite there being no single factor with significant The statistical analysis and inferences made are however valid. There are a few editorial issues that could be easily resolved by the authors e.g some minor typos with regard to the use of upper or lower case letters with regard to nouns. Another grammatical error that could be corrected is in paragraph 2 of the section titled “Factors associated with bacterial resistance to the third generation cephalosporins”. The first sentence of in this second parapraph reads “Higher odds of bacterial resistance to more 2 brands of the third generation cephalosporins….”. Did the authors mean to sate “2 brands or more”, or “more than 2 brands”? This should be clarified. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0261264.r001
Revision 1
10 Nov 2021 Author Response Response to Reviewers: Preamble: this document outlines the changes/revisions made as a result of review process made. All revisions have been written in red colour. This document consists of two main sections (journal requirements and Review Comments to the Author). The authors have also made the following minor changes; -The phrase ‘’infected chronic wound’’ is changed to “chronic wound infection” throughout the revised manuscript. - Additional affiliation (5) was added in the revised manuscript were the first author works as a head of department. (a)Journal 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. Response: All major section headings are level headings; bold with font size 18 throughout the revised manuscript, sub-headings are level 2 headings, bold and font size 16 while headings under subheadings are level 3 headings, bold and font size 14. All first letters of the headings are now capitalized. We also introduced cells in table 4 as per the above guidelines. See page 16. Equations have been restated using equation tool (page 6-7). Figure 1 has been removed from the manuscript body and submitted separately. Figure title and legend have been stated on page 14. Title, authors and affiliations have been revised as per PLOS ONE guidelines above. 2. Thank you for stating the following financial disclosure: “This study had no funding support from any organization/Institution. The corresponding author used out-of- pocket to fund this study as part of his postgraduate studies at Mbarara University of Science and Technology. All the remaining authors did not receive any grant to support this study but contributed non-financial support to this study.” At this time, please address the following queries: a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b) State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c) If any authors received a salary from any of your funders, please state which authors and which funders. d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Response: The authors have revised the above statement and the new statement of financial disclosure is “The authors received no specific funding for this work.” See page 20 under declaration section. 3.Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: Amendments have been stated in the cover letter and Witten in red color in the cover letter. 4. Thank you for stating the following in your Competing Interests section: The following authors had no financial and non-financial competing interest; 1. W.K 2. J.M 3. T.M 4. T.S.S Please complete your Competing Interests on the online submission form to state any Competing Interests. If you have no competing interests, please state ""The authors have declared that no competing interests exist."", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now Response: we have revised the above statement and the new statement is “The authors have declared that no competing interests exist” see competing interest on page 20 of the revised manuscript with track changes highlighted in red color. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ Response: The corresponding author has authenticated his pre-existing ID in the editorial manager. The ORCID ID is 0000-0002-5446-9352. 6. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Response: The ethics statement has been removed ‘’declaration sections’’ and ‘’selection criteria’’ and now appears only in methods section of the revised manuscript with track changes on page 4 under methods section. 7. 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. Response: Reference list has been reviewed. It is complete and correct. (b) Review Comments to the Author 1. While the study objectives are listed in the abstract there is no mention of the objectives in the methodology sections. It is not clear whether the authors differentiated between hospital or community acquired chronic wound infections given that this may influence antibiotic resistance patterns. Response: We (the authors) have clarified on page 5 under study population we studied community acquired chronic wound infection. This has been stated also in objective 1 on page 12 under subsection “data processing and analysis plan” 2. While there was a consideration for ≤2 prior hospitalizations it is not clear whether “0” or no hospitalization was also evaluated. Response: we only considered patients with at least 1 hospitalization in a year. See a caption under table 4 has been included to clarify this on page 16. 3. While the background section mentions some comorbidities as factors contributing to bacterial resistance the authors do not state what comorbidities the study participants were evaluated for. Response: We studied patients with chronic wound infection who had diabetes mellitus and hypertension. This has now been included under subsection “selection criteria’’ on page 6 of the revised manuscript. 4. There are a few editorial issues that could be easily resolved by the authors e.g some minor typos with regard to the use of upper or lower case letters with regard to nouns. Response: We have made various corrections regarding minor typos with regard to the use of upper or lower case letters with regard to nouns, particularly names of drugs, isolates and other nouns throughout the revised manuscript. See highlighted the first letters of various nouns that have been capitalized e.g. page 1 under subsection ’’results’’ of the abstract and page 14 under subheading “resistance pattern of chronic wound isolates” 5. Another grammatical error that could be corrected is in paragraph 2 of the section titled “Factors associated with bacterial resistance to the third generation cephalosporins”. The first sentence of in this second parapraph reads “Higher odds of bacterial resistance to more 2 brands of the third generation cephalosporins….”. Did the authors mean to sate “2 brands or more”, or “more than 2 brands”? This should be clarified. Response: The grammatical error has been resolved. We have stated “more than 2 brands” see paragraph 2 on page 15 under subsection “factors associated with bacterial resistance to third generation cephalosporins” Attachments Attachment Submitted filename: Response _to_ Reviewers.docx https://doi.org/10.1371/journal.pone.0261264.r002
26 Nov 2021 Decision Letter - Grzegorz Woźniakowski, Editor Resistance pattern of infected chronic wound isolates and factors associated with bacterial resistance to third generation cephalosporins at Mbarara Regional Referral Hospital, Uganda. PONE-D-21-22072R1 Dear Dr. Khalim, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Grzegorz Woźniakowski, Full professor, PhD, ScD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0261264.r003
Formally Accepted
6 Dec 2021 Acceptance Letter - Grzegorz Woźniakowski, Editor PONE-D-21-22072R1 Resistance pattern of infected chronic wound isolates and factors associated with bacterial resistance to third generation cephalosporins at Mbarara Regional Referral Hospital, Uganda. Dear Dr. Khalim: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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 Prof. Grzegorz Woźniakowski Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0261264.r004

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