Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing

Jade Chen; Su Su Soe San; Amelia Kung; Michael Tomasek; Dakai Liu; William Rodgers; Vincent Gau

doi:10.1371/journal.pone.0263868

Peer Review History

Original SubmissionApril 7, 2021
8 Jul 2021 Decision Letter - Arumugam Sundaramanickam, Editor PONE-D-21-08657 Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing PLOS ONE Dear Dr. Gau, 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 22 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. 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: http://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, Arumugam Sundaramanickam, PhD 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. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: - https://journals.asm.org/doi/10.1128/jcm.01999-17?permanently=true The text that needs to be addressed involves the second paragraph of the Discussions section. In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. [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: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: N/A ****** 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: No 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: Summary of the manuscript: I would like to appreciate the authors for their efforts, overall ideology and execution of the work is commendable. But language of the manuscript is not upto the mark, it has lots of grammatical errors and improper sentence formations. The manuscript needs an extensive review of the English language, hence this manuscript can’t be considered for publication in the same format. Specific corrections Avoid general statements, results and discussions in the methodology part, it can be included in respective sections of the manuscript. Authors may avoid some unsound words in manuscript such as, very, see etc. Authors may provide figures with high clarity Reviewer #2: The manuscript “Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing” proposes an antimicrobial efficacy profiling method that can be performed in hours directly from clinical urine specimens. The study seems very interesting, and clearly advances the current science. Although authors have worked on an interesting area of research, the figure quality is too poor to judge the manuscript. I am unable to read anything; the printing was also not helpful. Please submit higher resolution images for proper review. Please avoid abbreviations in the abstract. Also, adding a graphical abstract will be helpful for the readers of Plos one. ****** 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 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. Attachments Attachment Submitted filename: Plos.docx https://doi.org/10.1371/journal.pone.0263868.r001
Revision 1
29 Jul 2021 Author Response Response to Reviewers PONE-D-21-08657 Dear Editor, We would like to thank you and the reviewers for taking the time to consider our work and provide feedback. We appreciate the reviewers’ detailed feedback, which has proved to be helpful in improving the quality of our manuscript. We have adjusted our manuscript accordingly and addressed each comment in italics with references to the clean copy of the revised manuscript. 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 Response: We have ensured our manuscript meets journal requirements: figure and table references, figure and table captions and legends, section headings, etc. 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: - https://journals.asm.org/doi/10.1128/jcm.01999-17?permanently=true The text that needs to be addressed involves the second paragraph of the Discussions section. In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Response: We have amended lines 482-490 to address the overlapping text. We have also checked all citations for other instances of overlapping text. 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: Partly Reviewer #2: Partly Response: We have added the number of data points for each graph in each figure caption. We have also revised the statistical analysis section (line 170) to provide more details. ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: N/A Response: We have added the number of data points for each graph in each figure caption. We have also revised the statistical analysis section (line 170) to provide more details. ________________________________________ 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: No Reviewer #2: Yes Response: We have made changes throughout the manuscript to more clearly present our research findings and enhance the flow of content. ________________________________________ 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: Summary of the manuscript: I would like to appreciate the authors for their efforts, overall ideology and execution of the work is commendable. But language of the manuscript is not upto the mark, it has lots of grammatical errors and improper sentence formations. The manuscript needs an extensive review of the English language, hence this manuscript can’t be considered for publication in the same format. Response: We have made changes throughout the manuscript to more clearly present our research findings and enhance the flow of content. Specific corrections Avoid general statements, results and discussions in the methodology part, it can be included in respective sections of the manuscript. Response: We have removed such statements from the methods section. Authors may avoid some unsound words in manuscript such as, very, see etc. Response: We have made changes throughout the manuscript to address this concern. Authors may provide figures with high clarity Response: We have improved the quality of the figures. Reviewer #2: The manuscript “Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing” proposes an antimicrobial efficacy profiling method that can be performed in hours directly from clinical urine specimens. The study seems very interesting, and clearly advances the current science. Although authors have worked on an interesting area of research, the figure quality is too poor to judge the manuscript. I am unable to read anything; the printing was also not helpful. Please submit higher resolution images for proper review. Please avoid abbreviations in the abstract. Also, adding a graphical abstract will be helpful for the readers of Plos one. Response: We have removed all abbreviations in the abstract. We have improved the quality of the figures and the surrounding text. We have included a graphical abstract (Fig 1) illustrating the presented method in line 76. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0263868.r002
6 Dec 2021 Decision Letter - Mehmet A Orman, Editor PONE-D-21-08657R1 Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing PLOS ONE Dear Dr. Gau, Thank you for submitting your manuscript to PLOS ONE. The 2nd reviewer has raised a few minor issues regarding the literature discussed and statistical analyses performed in the manuscript. Therefore, we invite you to submit a revised version of the manuscript that addresses these minor points. Please submit your revised manuscript within a month. 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, Mehmet A Orman 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. [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: (No Response) ******** 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: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: All the comments have been addressed by authors, I would like to recommend this manuscript for the publication. Reviewer #2: The paragraph “Even though antibiotics do not directly affect the SARS-CoV-2 respiratory virus responsible for the COVID-19 48 pandemics, physicians are administering many more antibiotics than normal when treating COVID-19 patients 49 [2]. As published in the New England Journal of Medicine, 58.0% of the surveyed 1,099 COVID-19 patients 50 received intravenous antibiotic therapy in China, whereas 35.8% received oseltamivir antiviral therapy [3]. The 51 appearing surge in antibiotic use is reflected in the higher percentages of COVID-19 patients with severe 52 conditions and pediatric patients (85% in a multicenter pediatric COVID-19 study [4]) receiving antibiotic 53 therapies. The World Health Organization warned that the use of antibiotic therapy may lead to higher bacterial 54 resistance rates and increase the burden of the pandemic [5]. As viral respiratory infections often lead to bacterial 55 pneumonia, physicians may struggle to identify the causative pathogen in lung infections. A recent study by Zhou 56 et al. [6] found that 15% of 191 hospitalized COVID-19 patients, as well as 50% of the 54 non-survivors, acquired 57 bacterial infections. Major outbreaks of other respiratory viruses illustrated the same concern. For example, the 58 majority of deaths from the 1918 flu showed autopsy results consistent with bacterial pneumonia, and up to half 59 of the 300,000 non-survivors of the 2009 H1N1 flu were confirmed to have died from pneumonia [7-8]. Therefore, 60 a shorter time to rule out certain antibiotic options by detecting microbial growth under such conditions may 61 provide physicians with valuable information before the availability of conventional AST results,” contains some irrelevant information and it must be shortened. Where statistical analyses are described, please specify what formal tests for normality were used to assess data distribution. All data should be subject to tests for normality. Data that do not exhibit a normal/Gaussian distribution should be analyzed via a non-parametric equivalent. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [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.0263868.r003
Revision 2
22 Dec 2021 Author Response Dear Editor, We would like to thank you and the reviewers for considering our manuscript for publication. We appreciate the time and effort taken to provide feedback. Although comments were minor, we believe they were helpful to ensure the best version of our manuscript. We have addressed all comments below in italics and have referenced the manuscript with tracked changes in our responses. 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: (No Response) 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: Partly Response: We have added statistical analysis in the supporting information. Please see response below. 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No Response: We have added statistical analysis in the supporting information. Please see response below. 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: All the comments have been addressed by authors, I would like to recommend this manuscript for the publication. Response: We thank you for your time and support. Reviewer #2: The paragraph “Even though antibiotics do not directly affect the SARS-CoV-2 respiratory virus responsible for the COVID-19 48 pandemics, physicians are administering many more antibiotics than normal when treating COVID-19 patients 49 [2]. As published in the New England Journal of Medicine, 58.0% of the surveyed 1,099 COVID-19 patients 50 received intravenous antibiotic therapy in China, whereas 35.8% received oseltamivir antiviral therapy [3]. The 51 appearing surge in antibiotic use is reflected in the higher percentages of COVID-19 patients with severe 52 conditions and pediatric patients (85% in a multicenter pediatric COVID-19 study [4]) receiving antibiotic 53 therapies. The World Health Organization warned that the use of antibiotic therapy may lead to higher bacterial 54 resistance rates and increase the burden of the pandemic [5]. As viral respiratory infections often lead to bacterial 55 pneumonia, physicians may struggle to identify the causative pathogen in lung infections. A recent study by Zhou 56 et al. [6] found that 15% of 191 hospitalized COVID-19 patients, as well as 50% of the 54 non-survivors, acquired 57 bacterial infections. Major outbreaks of other respiratory viruses illustrated the same concern. For example, the 58 majority of deaths from the 1918 flu showed autopsy results consistent with bacterial pneumonia, and up to half 59 of the 300,000 non-survivors of the 2009 H1N1 flu were confirmed to have died from pneumonia [7-8]. Therefore, 60 a shorter time to rule out certain antibiotic options by detecting microbial growth under such conditions may 61 provide physicians with valuable information before the availability of conventional AST results,” contains some irrelevant information and it must be shortened. Response: We have removed irrelevant information and shortened the paragraph in lines 47-61. Where statistical analyses are described, please specify what formal tests for normality were used to assess data distribution. All data should be subject to tests for normality. Data that do not exhibit a normal/Gaussian distribution should be analyzed via a non-parametric equivalent. Response: The main premise of this paper is to demonstrate the feasibility of a direct-from-specimen AST that does not require clinical isolates as most current FDA-approved and CLSI methods do. A larger sample size for testing of clinical samples would be our next step to further validate the clinical utility of the presented method, and the normality test would then be essential for that future study. However, we have taken your suggestion and added a paragraph to the statistical analysis section (lines 205-211) to explain our normality tests for the negative and growth controls. Additionally, we reference and briefly explain each supplemental figure in lines 251-255, 282-284, and 317-322. In the future study using a larger sample size of blinded clinical samples, the microbial load distribution would not be predictable and therefore not normal, as samples could be negative, high positive, or weak positive (>80% of culture samples are reported negative). 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0263868.r004
31 Jan 2022 Decision Letter - Mehmet A Orman, Editor Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing PONE-D-21-08657R2 Dear Dr. Gau, 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, Mehmet A Orman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0263868.r005
Formally Accepted
7 Feb 2022 Acceptance Letter - Mehmet A Orman, Editor PONE-D-21-08657R2 Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing Dear Dr. Gau: 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 Dr. Mehmet A Orman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0263868.r006

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