Early Administration of Rifampicin Does Not Induce Increased Resistance in Septic Two-Stage Revision Knee and Hip Arthroplasty

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors carried out a retrospective study assessing the prevalence of rifampicin resistance and its characteristics. Following comments may be useful to authors:

1. Rifampicin was administered in combination with other antimicrobial drugs. What are the combinations observed following oral and intravenous administrations?
2. Could sub-group analyses be carried out between different combinations?
3. Are there data regarding the patients compliance following oral therapy? How does this influence the development of resistance in your patient cohort?
4. Were there any comorbid immunosuppressive disordes such as poorly controlled diabetes or other concomitant medicines that could potentially induce the development of resistance in your patient cohort?
5. How was the sample size estimated in your study?
6. Please adhere to EQUATOR reporting guidelines for retrospective studies.
7. Provide a checklist filling the page numbers related to each of the items in the reporting guidelines.
8. In the discussion, provide the strengths of your study with future directions to the practicing clinicians and researchers.  

Author Response

Reviewer 1:

Thank you very much for reviewing our paper and the helpful comments. Are the comments are addressed in new version. The answers to the comments are here in red and the changes in the manuscript also in red.

 

The authors carried out a retrospective study assessing the prevalence of rifampicin resistance and its characteristics. Following comments may be useful to authors:

1. Rifampicin was administered in combination with other antimicrobial drugs. What are the combinations observed following oral and intravenous administrations? Answer: This is added in Table 2 and 3
2. Could sub-group analyses be carried out between different combinations? Answer: Because of the small numbers of restistance a aub-group analyses could not be performed. This is mentioned as a limitation in the discussion section.
3. Are there data regarding the patients compliance following oral therapy? How does this influence the development of resistance in your patient cohort? Answer: There are no real data regarding patient compliance. We only think that the patients took the medication.
4. Were there any comorbid immunosuppressive disordes such as poorly controlled diabetes or other concomitant medicines that could potentially induce the development of resistance in your patient cohort? Answer: The comorbidities are listet in Table 1 and the Charlson Comobidity Index is mentioned below the table 1.
5. How was the sample size estimated in your study? Answer: A power analysis was made, assuming a rate of resistance around 10 %.
6. Please adhere to EQUATOR reporting guidelines for retrospective studies. Answer: This is done
7. Provide a checklist filling the page numbers related to each of the items in the reporting guidelines. Answer: the checklist is added at the end. The organization of the different sections is according to the style of the journal.
8. In the discussion, provide the strengths of your study with future directions to the practicing clinicians and researchers. Answer: is done at the end of the discussion section

9.  
10. STROBE Statement—Checklist of items that should be included in reports of cohort studies

 

	Item No	Recommendation	Lines No
Title and abstract	1	(a) Indicate the study’s design with a commonly used term in the title or the abstract	1-4
		(b) Provide in the abstract an informative and balanced summary of what was done and what was found	13-31
Introduction
Background/rationale	2	Explain the scientific background and rationale for the investigation being reported	34-62
Objectives	3	State specific objectives, including any prespecified hypotheses	63-79
Methods
Study design	4	Present key elements of study design early in the paper	224-227
Setting	5	Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection	228-235
Participants	6	(a) Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up	233-269
		(b) For matched studies, give matching criteria and number of exposed and unexposed
Variables	7	Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable	311-341
Data sources/measurement	8*	For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group	247-277, 279-341
Bias	9	Describe any efforts to address potential sources of bias	228-244
Study size	10	Explain how the study size was arrived at	227-232
Quantitativevariables	11	Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why	247-255
Statistical methods	12	(a) Describe all statistical methods, including those used to control for confounding	345-353
		(b) Describe any methods used to examine subgroups and interactions
		(c) Explain how missing data were addressed
		(d) If applicable, explain how loss to follow-up was addressed
		(e) Describe any sensitivity analyses
Results
Participants	13*	(a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed	82-91
		(b) Give reasons for non-participation at each stage
		(c) Consider use of a flow diagram	114
Descriptive data	14*	(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders	93-108
		(b) Indicate number of participants with missing data for each variable of interest
		(c) Summarise follow-up time (eg, average and total amount)
Outcome data	15*	Report numbers of outcome events or summary measures over time	87-99, 106-108

 

Main results	16	(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included	93-100,  106-113
		(b) Report category boundaries when continuous variables were categorized
		(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period
Other analyses	17	Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses	101-105, 122-127
Discussion
Key results	18	Summarise key results with reference to study objectives	130-133
Limitations	19	Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias	210-222
Interpretation	20	Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence	134-208
Generalisability	21	Discuss the generalisability (external validity) of the study results	355-361
Other information
Funding	22	Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based	369

 

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript can benefit from a clearer structural distinction between primary outcomes (rifampicin resistance) and secondary (reinfection rates) as the current results section tends to blend these which reduce clarity for readers. The discussion does not sufficiently address variables (comorbidities, previous revisions, differences in pathogen profiles) which could influence outcomes. The limitations of a retrospective design regarding data completeness and lack of a control group are acknowledged only briefly and need a more analysis to add to the strength of the conclusions. Several phrases in the manuscript are awkward or incorrect grammar ("continuously infection parameters") and a thorough language revision is necessary. Some references show minor formatting inconsistencies, and a detailed citation check is recommended. While the clinical relevance is ok the conclusion section does not translate the findings into practical recommendations or changes in clinical guidelines/ decisions. The title is relevant.

Comments on the Quality of English Language

Several phrases in the manuscript are awkward or incorrect grammar ("continuously infection parameters") and a thorough language revision is necessary.

Author Response

Reviewer 2:

Thank you very much for reviewing our paper and the helpful comments. Are the comments are addressed in new version. The answers to the comments are here in red and the changes in the manuscript also in red.

 

The manuscript can benefit from a clearer structural distinction between primary outcomes (rifampicin resistance) and secondary (reinfection rates) as the current results section tends to blend these which reduce clarity for readers. Answer: The result section is rewritten in this way

The discussion does not sufficiently address variables (comorbidities, previous revisions, differences in pathogen profiles) which could influence outcomes. Answer: This is mentioned as a limitation in the last paragraph of the discussion section.

 The limitations of a retrospective design regarding data completeness and lack of a control group are acknowledged only briefly and need a more analysis to add to the strength of the conclusions. Answer: This has been discussed in more detail in the limitations in the last paragraph of the discussion section.

Several phrases in the manuscript are awkward or incorrect grammar ("continuously infection parameters") and a thorough language revision is necessary. Answer: The paper has been reviewed by a nativ speaking scientist.

Some references show minor formatting inconsistencies, and a detailed citation check is recommended. Answer: The references have been corrected

While the clinical relevance is ok the conclusion section does not translate the findings into practical recommendations or changes in clinical guidelines/ decisions. Answer: This has been described in more detail in the conclusion section.

The title is relevant. Answer: No comment necessary

 

Reviewer 3 Report

Comments and Suggestions for Authors

Following are my comments and suggestions that the author should address to improve the manuscript:

1. Line 16 – The term "combination therapy" is unclear and potentially confusing. Please clarify or provide additional context.

2. Figure 1 – The figure legend titled "Schematic study course" needs further elaboration. Please describe the elements and flow of the schematic in more detail to enhance reader understanding.

3. It is unclear whether the study was conducted on a state-wise or country-wise basis. Please specify the geographical scope of the study.

4. The manuscript focuses solely on rifampicin. Please justify this choice, considering that there are several other antibiotics and antifungals that can also be administered to patients.

5. The dosage of rifampicin should be discussed in the manuscript, as it is a critical factor influencing the development of antibiotic resistance mechanisms in pathogens.

6. A comparative analysis with other antibiotics would strengthen the study. Please consider including a comparison to support the relevance and effectiveness of rifampicin in this context.

Author Response

Reviewer 3:

Thank you very much for reviewing our paper and the helpful comments. Are the comments are addressed in new version. The answers to the comments are here in red and the changes in the manuscript also in red.

 

Following are my comments and suggestions that the author should address to improve the manuscript:

1. Line 16 – The term "combination therapy" is unclear and potentially confusing. Please clarify or provide additional context. Answer: This has been rewritten
2. Figure 1 – The figure legend titled "Schematic study course" needs further elaboration. Please describe the elements and flow of the schematic in more detail to enhance reader understanding. Answer: The figure legend has been rewritten
3. It is unclear whether the study was conducted on a state-wise or country-wise Please specify the geographical scope of the study. Answer: This has been described at the beginning of the material and method section in more detail.
4. The manuscript focuses solely on rifampicin. Please justify this choice, considering that there are several other antibiotics and antifungals that can also be administered to patients. Answer: This was already mentioned in lines 50 and 56 and has been mentioned in line 250 as well as in the limitations of the discussion section in more detail.
5. The dosage of rifampicin should be discussed in the manuscript, as it is a critical factor influencing the development of antibiotic resistance mechanisms in pathogens. This is mentioned in more detail in the discussion section.
6. A comparative analysis with other antibiotics would strengthen the study. Please consider including a comparison to support the relevance and effectiveness of rifampicin in this context. Answer: This is mentioned in the limitations of the discussion section

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thanks for the revision.

Reviewer 3 Report

Comments and Suggestions for Authors

Accept