PONE-D-20-20807

Geographical distribution of Enterobacteriaceae with a carbapenemase IMP-6 phenotype and its association with antimicrobial use: an analysis using comprehensive national surveillance data on antimicrobial resistance

PLOS ONE

Dear Dr. Hirabayashi,

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Please address all comments of the referee point by point

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Iddya Karunasagar

Academic Editor

PLOS ONE

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There are some minor changes in the manuscript suggested by the reviewer. Please address these point by point.

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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: Yes

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

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: I would like to thank the editors for sending me such an interesting and relevant manuscript to review. I believe that the findings from this study are very important and have the ability not only to inform antimicrobial stewardship, but provide a good example of for other countries to investigate their own antimicrobial resistance and usage relationships.

I have a few comments for the authors, which I hope are of use.

General

- Would the authors consider using more current taxonomy i.e. Enterobacterales as opposed to Enterobacteriaceae [https://doi.org/10.1099/ijsem.0.001485]?

- Use a consistent approach to reporting p-values e.g. 1 significant figure, 2 decimal places etc.

Line 38: Suggest remove “This examination revealed a skewed frequency distribution.” This sentence means nothing in isolation.

Line 39-40: Were high rates observed in prefectures with high levels of 3GC prescribing? If so, suggest this sentence is merged with following sentence.

Line 44 and throughout: Remove “not carbapenems”. I don’t think you need to precede your 3GC observations with “not carbapenems” after the first mention.

Abstract: Could you conclude the abstract with a public health/antimicrobial stewardship recommendation? I believe the findings are important and actionable.

Line 53: Change “species” to “genera”

Line 63-65: This is a repeated statement – you have already stated that IMP carbapenemases are plasmid-mediated etc. earlier in the Introduction.

Lines 80-87: Summarise this section further. Suggest remove sentences between line 81 and 85 as you have already referenced the study and therefore detailed findings do not need to be provided.

Lines 92-96. This statement would be better placed in the Discussion, to highlight the advantages of the study design.

Lines 104-111: This reads more like an introduction of the methods. Suggest ending the Introduction by stating the aim(s) of your study.

Line 125: Defined daily dose = DDD

Line 160: Change “species” to “genera”

Lines 163-166: The detail in this sentence is superfluous since you have described the dataset and study years in the Methods. Suggest the sentence is simplified.

Line 168: Add “respectively” after “2016”.

Line 178: Provide the actual number (since this is the frequency) with the proportion in brackets immediately afterwards.

Line 179-180: This needs to precede the reporting of frequency and associated proportions. Also need to clarify what this “average” represents, and the type of “average” reported i.e. mean, median, mode?

Line 185: Change “average” to “median”.

Lines 191-192: Report 2015 data before 2016 (as you have done for the rest of the manuscript).

Lines 199-200: It is not clear which p-value relates to which specimen type.

Lines 206-210: This statement is more suited to the Discussion.

Lines 211-215: Much of this is already covered in the Methods and can be removed.

Lines 215-218: The wording of this goes beyond reporting the results, introducing elements of interpretation, which belongs in the Discussion.

Lines 241-242: If the proportion of Enterobacter cloacae is so high, why were these isolates not included in the study? An explanation in the Introduction or Methods (depending on reason) may be necessary.

Lines 242-245: This information belongs in the Results.

Lines 262-265: This information belongs in the Results.

Lines 269-271: Is there a reference for this?

Figure 1: The category “<1” does not make sense in the legend.

Figure 3: I think this data would be better presented as a table.

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Reviewer #1: No

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Geographical distribution of Enterobacterales with a carbapenemase IMP-6 phenotype and its association with antimicrobial use: an analysis using comprehensive national surveillance data on antimicrobial resistance

PONE-D-20-20807R1

Dear Dr. Hirabayashi,

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,

Iddya Karunasagar

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All reviewer comments addressed

Reviewers' comments: