PONE-D-24-46598The effect of antibiotic prescription in non-critically ill hospitalized patients with COVID-19: A Japanese inpatient database study

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Editor's comments:

Line 58-60: "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can progress from mild symptoms to acute respiratory distress syndrome with high mortality rate, hence a global pandemic": More references need to be cited, with these ones (PMID: 33337932 and 33667962) as examples (citing is optional).

line 212, Discussion: "Antibiotic use benefits may be observed in high-risk patients.": More references need to be cited, with this one (PMID: 34406882) as an example (citing is optional).

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Real-world retrospective analyses benefited from the compilation of previous data from databases. The paper evaluated the impact of antibiotic prescribing on COVID-19 non-critically ill patients by analyzing the Japanese inpatient database, including analysis of mortality, secondary nosocomial infections, and hemodialysis, which provides a valuable reference value for clinicians or researchers, in terms of treatment and prognosis.

The paper itself is logically clear, with concise arguments and clear statistics. However, even if anonymized data is purchased, please provide proof of the appropriate ethical license for this study as required by the journal.

Reviewer #2: This study aimed to evaluate the effects of antibiotic prescriptions in non-critically ill COVID-19 patients using a Japanese multicenter inpatient database.

While antibiotics help manage secondary bacterial infections, they also come with risks. The first thing that comes to mind is that antibiotic prescriptions are known to cause diarrhea as a side effect.

In this study, the authors used Clostridioides difficile infection (CDI) and acute kidney injury (AKI) as measures of the side effects of antibiotic usage, while 28-day mortality and in-hospital mortality were assessed as beneficial outcomes.

the definition of "mortality" in this study is unclear. Is it attributed to COVID-19 or other causes? The authors should clarify how they distinguish between COVID-related and unrelated mortality to improve the interpretability of their results

Introduction :The Introduction does not provide enough background information. While I didn’t search extensively, I believe there are existing papers or case reports discussing the benefits of antibiotic prescriptions for COVID-19 patients. Given that excessive antibiotic use is becoming a significant issue, I recommend the authors include more context on the benefits and side effects of antibiotic prescriptions in this population.

Methods: The terms Clostridioides difficile infection (CDI) and acute kidney injury (AKI) need clearer definitions in Lane 130.

Results: The baseline characteristics of the participants appear balanced, which is a strength of the study.

Discussion: The discussion section should compare the results with other available data. For instance, the WHO has stated that "overall, antibiotic use did not improve clinical outcomes for patients with COVID-19 and may cause harm to individuals without bacterial infections compared to those not receiving antibiotics." Including such comparisons would contextualize the findings and add depth to the discussion.

First thing jump to my head is that The side effect of antibiotic prescription is reported to casuse diarrhea. Ref: Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection. The good part is antibiotics deal with secondary bacteria infection.

In this study, the author used CDI and AKI as measures of side effect of antibiotic usage, and use 28-day mortality rate and In-hospital mortality as the beneficial side outcomes.

In term of “mortality”, it is not well defined in this study. Is it from covid or others? And how to distinguish one from another.

Introduction doesn’t provide enough information/background: to be honsst, I didn’t search carefully but. I believe there should be some papers/case reports talking about the benefitcial of antibiotic prescribing to patients. becasue Now the excessive usega of antibiotics is becoming a problem. In this case, I would suggest authors to : Add some context about the benefits or side effect of antibiotix prescription on covid patients .

Definition of CDI and AKI: Clostridioides difficile infection (CDI) and acute kidney injury (AKI). Lane 130 need a clearer definition.

Result: the Baseline characteristics of the participants are balanced

Discussion section shold also discuss the result comparing with other available data. For example,WHO announced: Overall, antibiotic use did not improve clinical outcomes for patients with COVID-19 and also . But rather, it might create harm for people without bacterial infection, compared to those not receiving antibiotics’

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Reviewer #1: No

Reviewer #2: No

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The effect of antibiotic prescription in non-critically ill hospitalized patients with COVID-19: A Japanese inpatient database study

PONE-D-24-46598R1

Dear Dr. Kodama,

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,

Benjamin M. Liu, MBBS, PhD, D(ABMM), MB(ASCP)

Academic Editor

PLOS ONE

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