PONE-D-22-04577Antibiotic treatment duration for bacteremia in critically ill children--a survey of pediatric infectious diseases and critical care clinicians for clinical equipoisePLOS ONE

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Additional Editor Comments:

While paper is one of much interest, the analyses of the data obtained requires more thought on the results and inferences. The reviewers have provided clear comments to be addressed which the authors are required to respond to.

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: Review of article entitled “Antibiotic treatment duration for bacteremia in critically ill children--a survey of pediatric infectious diseases and critical care clinicians for clinical equipoise” by S. Pong et al.

Major comments

Interesting study. The project is well designed and the results are presented clearly. The use of violin plots is judicious. I have the following comments to help improve the manuscript.

1. Abstract: could we indicate how many scenarios were presented? Perhaps mentioning that the survey focused on 5 common pediatric scenarios.

2. Respondents: could an individual answer the survey twice?

3. Invitation to participate: were reminders to participate sent to potential participants to improve response rate?

4. Could people forward the survey to other potential respondents? This can sometimes bias the response rate.

5. Analyses: From the survey, I understand that the answers regarding the number of days are continuous numerical values (i.e. respondents indicated the number of days they would recommend), not a multiple-choice question (e.g. 7, 10, 14 days). Consequently, I’m not sure to understand why the main outcome is presented as “the proportion of respondents who recommend >=10 days of antibiotics” (page 8, line 187). Presenting the results in this manner would be expected if the question had been a multiple choice question, but considering the type of data available, I would expect these results to be presented as a median number of days with IQR. Saying that “65% recommend at least 10 days of treatment for pneumonia” is not the same (and not as informative) as saying that the median duration is 10 days (IQR, 7-10). Actually, the former sentence gives the impression that the treatment duration recommendation is longer than it really is (looking at the violin chart, 50% of respondents recommend 10 days or less of treatment). This comment would also apply to the abstract.

6. Analyses: the authors state that they conducted a multivariable linear regression analysis using specialty, country, years of practice and ASP practice as independent variables. However, when I look at table 3 and read the discussion section (page 18, lines 329-332), I have the impression that only bivariate (univariate) analyses were performed. Indeed, conducting multiple univariate analyses is not the same thing as conducting a multivariate analysis. Please clarify whether multiple variables were entered simultaneously into a single model to identify independent predictors after adjusting for covariates.

7. As an additional analysis, I would be curious to know whether there is cross-correlation in terms of treatment duration recommendation for a given respondent. For example: is a respondent who recommend a longer treatment for a given infection also more likely to recommend a longer treatment for another type of infection? Identifying cross-correlation would allow to identify subgroups of “long-prescribers” and “short-prescribers”.

8. Table 3. A footnote to explain how to interpret the B-coefficient would be helpful.

9. Considering the small sample size and the multiple comparisons that were conducted between groups, I wonder whether the p-value should be adjusted for multiple comparisons and be lower than 0.05. This could prevent the identification of spurious findings.

Reviewer #2: In this study, Dr. Pong and colleagues aimed to understand typical practice patterns surrounding duration of therapy for bacteremia in pediatric patients. They designed an online survey that was administered to pediatric intensivists, nurse practitioners, ID physicians, and pharmacists. They report interesting data that should motivate RCTs in this area. Some minor comments below.

Abstract

Lines 59-60: This is a little unclear. I think that it would be helpful avoid the nested parentheses and perhaps use brackets instead. Also, make it more clear that the first set of numbers refers to lack of source control with intra-abdominal infections and second set of numbers refers to patients with central line infections

Lines 60: It would be helpful to clarify why there is a range here. Perhaps “73-95%, depending on source of bacteremia”

Lines 63-64: I don’t think that this concept of implicit versus explicit equipoise is going to be familiar to most readers and so it either warrants a brief explanation or just remove it. It would be important to point out how the results presented in the abstract support this statement.

Introduction:

Why transition in terminology between bacteremia (Abstract) and then BSIs (the rest)?

Results:

Lines 188-190: Why the different denominators for each infectious syndrome, and why none equal to 136? Participants had the option of not answering questions?

Table 3: It would be helpful to note that the beta-coefficient and CI represent days of therapy

Discussion:

Lines 327-335: Could consider omitting this paragraph. Identifying differences in treatment duration between the various subgroups is challenging given the overall low numbers in the subgroups and the different compositions of the subgroups (e.g., more ID providers in the New Zealand/Australia group).

Reviewer #3: This manuscript nicely describes the variability in AB prescription patterns for SBI in children. As expected, there is a wide range of treatment duration as beautifully showed in the violin plots, but the general duration is long (10-14 days) and to me always intriguing, durations are usually 5, 7, 10, 14 or 21 days, never a number in between.

The manuscript is very clear and well written. One question that came into my mind is how are the prescription patterns related to the national protocols? Did authors look at national protocols for paediatric SBI and compared those protocols with the answers of the respondents? This probably would be interesting to add although there is also variability within a country.

The manuscript is a good base for starting of a trial into duration of SBI treatment. I am wondering if there is any place for IV-oral switch in those SBIs (see review DOI: 10.1016/S1473-3099(16)30024-X) , this is nowhere mentioned by the authors and might be addressed in the discussion section.

Specific comments:

The introduction is very well written and covers the most important aspects of questions concerning antibiotic use. The review of McMullan could be referred to (DOI: 10.1016/S1473-3099(16)30024-X)

Line 228/229: is this sentence correct? Is should probably read longer durations after no removal of catheter?

Table 3: very interesting an ASP present does not lead to differences in treatment duration - authors could highlight this in the discussion.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: G.A. Tramper

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Antibiotic treatment duration for bloodstream infections in critically ill children—a survey of pediatric infectious diseases and critical care clinicians for clinical equipoise

PONE-D-22-04577R1

Dear Dr Pong,

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,

Jamunarani Vadivelu

Academic Editor

PLOS ONE

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