PONE-D-21-16139

Prevalence and antimicrobial resistance pattern of Clostridium difficile: a systematic review and meta-analysis

PLOS ONE

Dear Dr. Dilnessa,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Yung-Fu Chang

Academic Editor

PLOS ONE

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2. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author.

- https://www.researchsquare.com/article/rs-4263/v1

- https://www.sciencedirect.com/science/article/abs/pii/S1046592810001282?via%3Dihub

- https://www.sciencedirect.com/science/article/abs/pii/S1075996418300234?via%3Dihub

- https://aricjournal.biomedcentral.com/articles/10.1186/s13756-020-00815-5

- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244057

- https://www.nature.com/articles/srep37865?code=5bd7e315-eb97-43aa-965b-4f80e34626cd&error=cookies_not_supported

- https://www.tandfonline.com/doi/abs/10.1080/20477724.2019.1603003?journalCode=ypgh20

- https://www.hindawi.com/journals/ijmicro/2020/9461901/

- https://www.biomerieux.com.tr/sites/subsidiary_uk/files/c-difficile-booklet-final-update-2013_0.pdf

- https://www.sciencedirect.com/science/article/abs/pii/S0891552014000907?via%3Dihub

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current 

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study Dilnessa et al described presents a sustematic review and meta-analysis on prevalence and antimicrobial resistance pattern of C.difficile. C.difficile is the leading cause of infectious disease that has been concerned in most of countries. The data in this study were collected from some regions in the worldwide, and the results reported here were a little bias. The comments were presented as below.

1. In line 35, C.difficile has also become a big issue in community-acquired diarrhea.

2. In lines 13-16, this paragraph should be omitted. the paragraph in lines 16-19 should be an initial paragraph in Introduction.

3. In lines 7-10, the reference 5 published in 2009, the data in ref 5. did not display the data from the last decade.

4. In lines 10-11, the authors should provide the geographical information.

In lines 105-106, this is not an exclusion criteria. The authors should involve all the published data meeting inclusion criteria.

5. As figure 1 shown, only fifteen studies was too few to meet the study. I just searched C.difficle, molecular epidemiology, antimicrobial resistance/ susceptibility pattern in the PubMed. There were more than one hundred studies meeting the inclusion criteria. I strongly recommended that the authors involved more data into this study.

Minor comments:

1. In line 6, omit the letter"a".

2. In line 33, C.difficile producing....

3. In line 44, omit the letter"s".

4. In line 118, provide the full name of JBI.

5. There are some mistakes in Table 1, e.g. Peng Z and Wang R from China.

6. Please provide high resolution pictures as the figures.

Reviewer #2: This is a systematic review and meta-analysis of the prevalence of CDI and the prevalence of resistance to common antimicrobials of CD strains among hospitalised patients with diarrhea. The topic is of health care importance.

The study background appears sometimes partly outdated as CD resistance to most commonly used antibiotics is not an emerging issue but is a reality since at least 2 decades.

The title clearly describes the main focus but doesn’t mention the specific setting, i.e. hospitalised patients with diarrhea.

The abstract sums up the main contents of the work with coherence and effectiveness. However, it mentions hypervirulent strains that are not the focus of any specific evaluation. Also, it states CDI prevalence came out ‘higher’ but it is not clear with respect to which anticipated value.

The methods section reports all information about the study, along with inclusion and exclusion criteria.

Statistical analysis is well described.

Results are not always clearly presented. In the text, it is difficult to differentiate cases (i.e. patients with the disease) of CDI from strains evaluated for susceptibility. Often the impression is that authors failed to re-read the article for a final revision. Just as an example, sentence at line 236 appears truncated (it should read ‘for estimating the pooled resistance is applicable’).

Major comments:

1. A more clinically-relevant focus of the study would be to assess CD resistance to the 3 commonly used antimicrobials (vanco, metron, fidaxom) and some newer assessed options, that are only partly mentioned by authors, but not studied. Assessing prevalence of AMR for ciprofloxacin, clindamycin or erythromycin has much less relevance as none of these molecules are used for CDI treatment.

2. Inclusion of patients with diarrhea: were these patients who were admitted because of diarrhea or developed diarrhea during hospitalization for other reasons? Were patients on any antibiotic before or at the time of diarrhea onset?

3. Beyond formal evaluation of heterogeneity of results, it is significant to note the large difference in prevalence of CDI in the EU study and in the Iran+China studies. This requires authors to describe which were the diagnostic tools used for diagnosis (culture, toxigenic culture, GDH/toxin EIA, polymerase chain reaction?). The same applies for antimicrobial susceptibility testing: which were tests used and was any heterogeneity in terms of methodology used across studies?

4. At the beginning of Results section, authors repeat that studies had features already described in Methods, inclusion/exclusion criteria. These details are not needed in the Results and make the text too long.

5. Country of studies: Scotland and Poland are in Europe. It is odd that half of the studies included came from Iran. By the way, this makes generalizability of results much more problematic, also in light of the fact that Iranian studies weight was 70%. On double checking Table 1, ref. 50 Freeman is not from Iran, ref. 45 Mohammadbeigi is not from China but Iran. … I think most data regarding countries are wrong. Referring to the weighted pooled proportion authors define it as ‘worldwide’. This is not the case as the number of countries included is limited. The notation worldwide should be essentially removed.

6. Abstract Line 34: not necessarily after hospitalization; it is usually after antibiotic administration. Hospital emerging cases are the majority as community based diagnosis is more difficult.

7. A thorough revision of the English language is needed.

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Reviewer #1: Yes: Dazhi Jin

Reviewer #2: Yes: Emanuele Durante Mangoni, MD PhD

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PONE-D-21-16139R1Prevalence and antimicrobial resistance pattern of Clostridium difficile among hospitalized diarrheal patients: a systematic review and meta-analysisPLOS ONE

Dear Dr. Dilnessa,

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. Your manuscript has been reviewed by one of the previous reviewers and a minor revision  is required before a decision can be made.

Please submit your revised manuscript by two weeks. 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,

Yung-Fu Chang

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

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

Reviewer #1: 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

**********

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: No

**********

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: The revised manuscript has been improved and better than the previous one. However, the language needs to be checked and edited again. In line 370, the word "was" is corrected to "were". In line 371, The pooled resistances.....In line 376, no resistant strains have been identified...... e.g.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes: Dazhi Jin

[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.

Prevalence and antimicrobial resistance pattern of Clostridium difficile among hospitalized diarrheal patients: a systematic review and meta-analysis

PONE-D-21-16139R2

Dear Dr. Dilnessa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Yung-Fu Chang

Academic Editor

PLOS ONE

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