Dear Dr. Kebede,

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 Sep 14 2025 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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We look forward to receiving your revised manuscript.

Kind regards,

Tebelay Dilnessa, MSc

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

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2. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement.

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4. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments:

The paper requires intensive revision.

Avoid words like 'see figure 1' etc. It is better written as (Figure 1)

Follow the PLOS ONE manuscript writing protocol.

[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?

Reviewer #1: Partly

Reviewer #2: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

Reviewer #1: Dear Editors,

Thank you for inviting me to review the manuscript titled “Antibiotics Utilization Patterns among Tertiary Care Hospitals in Ethiopia.” The study addresses a critical public health issue and provides valuable insights for antimicrobial stewardship in low-resource settings. Below, I outline its strengths and key areas for improvement to enhance the manuscript’s rigor and impact.

Strengths:

• The manuscript is well-structured and contributes meaningfully to the literature on antibiotic use in sub-Saharan Africa.

• The application of WHO’s ATC/DDD methodology ensures standardized measurement of antibiotic consumption.

• Findings are actionable, particularly the overuse of "Watch" group antibiotics, which deviates from WHO recommendations.

Major Weaknesses and Recommendations:

1. Timeliness of Data:

The study was conducted three years ago, and antibiotic prescribing practices or resistance patterns may have since evolved. The authors should address how this temporal gap might affect the current relevance of their findings.

2. Ethical Approval/Consideration

While retrospective studies often involve anonymized data, the manuscript should explicitly state whether ethical approval (e.g., IRB reference number) was obtained to ensure compliance with research integrity standards.

3. Study Design Limitations:

o The retrospective cross-sectional design precludes causal inferences (e.g., linking prescribing patterns directly to resistance rates).

o Excluding outpatient and pediatric data omits significant antibiotic use contexts. Recommendation: Future studies should expand methodology to include these populations and integrate local antibiograms to correlate prescribing with resistance trends.

4. Generalizability Concerns:

o Findings from five public tertiary hospitals may not reflect practices in primary/secondary care or private sectors.

o Regional variability (4 regions) may not capture national heterogeneity. Recommendation: Acknowledge this limitation and suggest multi-center studies for broader applicability.

5. Methodological Gaps:

o The DDD metric does not account for dosing adjustments (e.g., renal impairment) or pediatric use.

o Clinical outcomes (e.g., treatment success, resistance emergence) are not analyzed. Recommendation: Discuss these limitations and propose linking future data to patient outcomes.

6. Presentation Issues:

o Tables 2–4 contain repetitive data and could be consolidated for clarity.

o A visual summary (e.g., bar chart of AWaRe group deviations from WHO targets) would improve readability.

7. Discussion Enhancements:

o Contextualize findings with regional AMR surveillance data (e.g., resistance rates for ceftriaxone).

o Compare results with Ethiopia’s AMR National Action Plan (if available) and propose specific stewardship interventions (e.g., audit/feedback, surgical prophylaxis guidelines).

8. Policy and Recommendations:

o Detail actionable strategies (e.g., formulary restrictions, prescriber education).

o Include cost-analysis of antibiotic misuse (e.g., budget impact of Watch-group overuse).

o Advocate for hospital-specific formularies prioritizing "Access" group antibiotics and training on de-escalation protocols.

Reviewer #2: Needs to work on English language presentation

What is the novelty of data in the study?

There is overall casual attitude in preparation of manuscript

Result: Table no 3, 5 and 6 are missing in the manuscript

Table no 2 mentions Drugs with drug name are mentioned as 1,2,3,4,5. This does not explain anything.

There is repetition of data presentation in the tables.

**********

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:  Bantayehu Addis Tegegne

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: Comment for the manuscript.docx

Dear Dr. Kebede,

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 15 2025 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.

• 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 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,

Tebelay Dilnessa, MSc

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

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:

• It is better the author order, ‘Materials and methods’
• The figure 1, description should be placed within the manuscript where cited below it.
• Poofread is also required.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

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

Reviewer #1: Yes

Reviewer #2: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

Reviewer #1: Dear Editors,

Thank you for inviting me to review the manuscript titled “Antibiotics Utilization Patterns among Tertiary Care Hospitals in Ethiopia.” The study addresses a critical public health issue and provides valuable insights for antimicrobial stewardship in low-resource settings. Below, I outline its strengths and key areas for improvement to enhance the manuscript’s rigor and impact.

Strengths:

• The manuscript is well-structured and contributes meaningfully to the literature on antibiotic use in sub-Saharan Africa.

• The application of WHO’s ATC/DDD methodology ensures standardized measurement of antibiotic consumption.

• Findings are actionable, particularly the overuse of "Watch" group antibiotics, which deviates from WHO recommendations.

Major Weaknesses and Recommendations:

1. Timeliness of Data:

The study was conducted three years ago, and antibiotic prescribing practices or resistance patterns may have since evolved. The authors should address how this temporal gap might affect the current relevance of their findings.

2. Ethical Approval/Consideration

While retrospective studies often involve anonymized data, the manuscript should explicitly state whether ethical approval (e.g., IRB reference number) was obtained to ensure compliance with research integrity standards.

3. Study Design Limitations:

o The retrospective cross-sectional design precludes causal inferences (e.g., linking prescribing patterns directly to resistance rates).

o Excluding outpatient and pediatric data omits significant antibiotic use contexts. Recommendation: Future studies should expand methodology to include these populations and integrate local antibiograms to correlate prescribing with resistance trends.

4. Generalizability Concerns:

o Findings from five public tertiary hospitals may not reflect practices in primary/secondary care or private sectors.

o Regional variability (4 regions) may not capture national heterogeneity. Recommendation: Acknowledge this limitation and suggest multi-center studies for broader applicability.

5. Methodological Gaps:

o The DDD metric does not account for dosing adjustments (e.g., renal impairment) or pediatric use.

o Clinical outcomes (e.g., treatment success, resistance emergence) are not analyzed. Recommendation: Discuss these limitations and propose linking future data to patient outcomes.

6. Presentation Issues:

o Tables 2–4 contain repetitive data and could be consolidated for clarity.

o A visual summary (e.g., bar chart of AWaRe group deviations from WHO targets) would improve readability.

7. Discussion Enhancements:

o Contextualize findings with regional AMR surveillance data (e.g., resistance rates for ceftriaxone).

o Compare results with Ethiopia’s AMR National Action Plan (if available) and propose specific stewardship interventions (e.g., audit/feedback, surgical prophylaxis guidelines).

8. Policy and Recommendations:

o Detail actionable strategies (e.g., formulary restrictions, prescriber education).

o Include cost-analysis of antibiotic misuse (e.g., budget impact of Watch-group overuse).

o Advocate for hospital-specific formularies prioritizing "Access" group antibiotics and training on de-escalation protocols.

Reviewer #2: Inclusion criteria are vague and lack specification. Antibiotics outside ELM were not included?

Inclusion criteria mentions “Antibiotics prescribed for initial diagnosis were included”. Please clarify.

Ethics permission from the registered ethics committee of each hospital participating in the study is required to collect data. Verbal permission may not be sufficient or authentic.

Study design: The study design is mentioned as “retrospective cross-sectional study”; however, the exact time point of data collection is not mentioned in the manuscript. Only the duration during which the data was assessed, as has been mentioned

Results: The number of female participants in the text and table is different. Data on SD is missing. The legend for Table 2 is not clear. What are 1,2,3,4,5,6,7, rounds of prescribing? Table 4: column 1st: What does drug 1,2,3,4,56,7 indicate?

There are multiple instances of spelling errors.

**********

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:  Bantayehu Addis Tegegne, Lecturer of Pharmacology at Debre Markos University, Debre Markos, Ethiopia

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

Antibiotics Utilization Patterns among Tertiary Care Hospitals in Ethiopia

PONE-D-25-34538R2

Dear Dr. Kebede,

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.

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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,

Tebelay Dilnessa, MSc

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: