Lines of Risk: Tunnel Catheter Loss Due to Bloodstream Infections in Chronic Hemodialysis Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for the opportunity to review your manuscript. The study addresses an important problem in hemodialysis patients, namely vascular access loss following bloodstream infections. Below I provide a concise assessment by section.

Background
The introduction correctly frames the burden of CRBSI but remains generic. It would be strengthened by positioning your work against contemporary hub-device strategies and infection-rate definitions. Recent review (Fiorina et al., 2024 10.1177/11297298241273559) summarizes the role of needle-free connectors and disinfecting port protectors, and explicitly discusses standardized CRBSI rates per 1,000 catheter-days. Citing this work would provide both epidemiological context and methodological justification.

Methods
The retrospective multicenter design is appropriate, but the calculation of CLABSI rates per 100 patient-months is unconventional and difficult to compare with international benchmarks. Whenever possible, rates should be expressed per 1,000 catheter-days, as recommended in dialysis surveillance literature (see Fiorina et al., 2024). Furthermore, definitions of contamination, CRBSI, and CLABSI need to be made explicit, and the rationale for excluding duplicate cultures clarified. Finally, the time-to-event analysis appears inconsistent with the study period and should be checked carefully.

Results
Your findings on the association of tunnel infection with access loss are important. However, the abstract and discussion currently emphasize unadjusted associations (BMI, Gram-negative pathogens), which lose significance in the multivariable model. Conclusions should be re-centered on adjusted results, highlighting tunnel infection as the most robust predictor.

Discussion
The discussion would benefit from integrating your results into the broader context of catheter-hub management. Bench evidence (Privitera et al., 2024, 10.1177/11297298241301508) shows that clamping is crucial to reduce backflow in dialysis catheters, while needle-free connectors alone do not abolish reflux. Linking this mechanistic work with your clinical findings would strengthen the rationale for comprehensive catheter-care bundles that combine infection prevention with occlusion control.

Conclusions
The manuscript offers valuable regional data, but its impact will be enhanced by: aligning infection-rate metrics with international standards, clarifying case definitions, centering conclusions on adjusted results, and situating findings within current hub-device literature. 

Author Response

Dear Authors,

Thank you for the opportunity to review your manuscript. The study addresses an important problem in hemodialysis patients, namely vascular access loss following bloodstream infections. Below I provide a concise assessment by section.

Background
The introduction correctly frames the burden of CRBSI but remains generic. It would be strengthened by positioning your work against contemporary hub-device strategies and infection-rate definitions. Recent review (Fiorina et al., 2024 10.1177/11297298241273559) summarizes the role of needle-free connectors and disinfecting port protectors, and explicitly discusses standardized CRBSI rates per 1,000 catheter-days. Citing this work would provide both epidemiological context and methodological justification.

(Good suggestion, I have added this citation in my conclusion as it will be appropriate to mention these advances in take home message)

Methods
The retrospective multicenter design is appropriate, but the calculation of CLABSI rates per 100 patient-months is unconventional and difficult to compare with international benchmarks. Whenever possible, rates should be expressed per 1,000 catheter-days, as recommended in dialysis surveillance literature (see Fiorina et al., 2024). Furthermore, definitions of contamination, CRBSI, and CLABSI need to be made explicit, and the rationale for excluding duplicate cultures clarified. Finally, the time-to-event analysis appears inconsistent with the study period and should be checked carefully.

(Our hospital infection control dept. follows CDC events reporting and they report as patients-month so our record is based accordingly, unfortunately it will not be possible to change analysis now). I have raised this concern to higher management to align data in future with international benchmarks.

Results
Your findings on the association of tunnel infection with access loss are important. However, the abstract and discussion currently emphasize unadjusted associations (BMI, Gram-negative pathogens), which lose significance in the multivariable model. Conclusions should be re-centered on adjusted results, highlighting tunnel infection as the most robust predictor.

(I have added 1 paragraph on tunnel infection significance on multivariate analysis in discussion)

Discussion
The discussion would benefit from integrating your results into the broader context of catheter-hub management. Bench evidence (Privitera et al., 2024, 10.1177/11297298241301508) shows that clamping is crucial to reduce backflow in dialysis catheters, while needle-free connectors alone do not abolish reflux. Linking this mechanistic work with your clinical findings would strengthen the rationale for comprehensive catheter-care bundles that combine infection prevention with occlusion control.

( I have added this citation in my conclusion as it will be appropriate to mention these advances in take home message)

Conclusions
The manuscript offers valuable regional data, but its impact will be enhanced by: aligning infection-rate metrics with international standards, clarifying case definitions, centering conclusions on adjusted results, and situating findings within current hub-device literature. 

(Done)

Reviewer 2 Report

Comments and Suggestions for Authors

This was a retrospective study of hemodialysis patients across 5 centres. The findings of greater loss with gram negative pathogens and high BMI are unsurprising. The pathogens were mainly staphylococci as expected. Hand hygiene, education and surveillance are recommended but it is unclear how this paper presents novel findings.

 

In the introduction, discussion should focus on catheter-related infection related to hemodialysis lines rather than catheters in general. The novel aims of the study should be described – if this is lack of publications in the geographical area any publications is there reason to suppose there will be unique factors.

 

The study was across 5 centres. Data was collected retrospectively so were all data collected using similar criteria in each centre? What was the definition of CLABSI? Statistical analysis was limited to descriptive measures.

 

As expected, increased risk of catheter loss was related to obesity and Gram negative pathogens. Central and peripheral blood culture results were similar but were there the same pathogens when both cultures were collected from the same patient? What were the other infections with AVF? CVC salvage with infection has a high risk of recurrence. Changing the line is usual, particularly in tunnel infections. If the policy is to remove lines when infected, then this will show the results obtained. Were these tunnelled lines and how were they salvaged? Successful salvage of tunnelled lines would be unusual. The progressive decline in access presumably means any access rather than just the same type of line – this should be explained. Gram negative pathogens may be associated with the type of topical agents used regularly during catheter site care.

 

The type of multivariable logistic regression should be described and cited rather than just mentioned in the methods section. Methods should be moved from results to methods.

 

The discussion includes failure rates by organism species. Were these studies confirmed in this investigation e.g. Pseudomonas aeruginosa. Higher rates of infection in obese patients is well recognised with any device. The advice under conclusions echoes standard guidelines. More emphasis should be put on conclusions from this study. As a limitation the five hospitals used may not be applicable to hospitals in other countries or even others in the same country.

Author Response

This was a retrospective study of hemodialysis patients across 5 centres. The findings of greater loss with gram negative pathogens and high BMI are unsurprising. The pathogens were mainly staphylococci as expected. Hand hygiene, education and surveillance are recommended but it is unclear how this paper presents novel findings.

(Our findings show improvement in gram negative prevalence as compared to previous data from Balkhy et al reference no 12 from our region, if further measures are taken it can significantly cut down gram negative bacteremia).

 

In the introduction, discussion should focus on catheter-related infection related to hemodialysis lines rather than catheters in general. The novel aims of the study should be described – if this is lack of publications in the geographical area any publications is there reason to suppose there will be unique factors.

(Introduction is mainly about tunnel catheters in dialysis, lack of data regionally is mentioned in last paragraph of introduction).

 

The study was across 5 centres. Data was collected retrospectively so were all data collected using similar criteria in each centre? What was the definition of CLABSI? Statistical analysis was limited to descriptive measures.

(Study was done with similar criteria in all 5 centers, CLABSI definition added in manuscript, Statistical analysis description added in method).

 

As expected, increased risk of catheter loss was related to obesity and Gram negative pathogens. Central and peripheral blood culture results were similar but were there the same pathogens when both cultures were collected from the same patient? What were the other infections with AVF? CVC salvage with infection has a high risk of recurrence. Changing the line is usual, particularly in tunnel infections. If the policy is to remove lines when infected, then this will show the results obtained. Were these tunnelled lines and how were they salvaged? Successful salvage of tunnelled lines would be unusual. The progressive decline in access presumably means any access rather than just the same type of line – this should be explained. Gram negative pathogens may be associated with the type of topical agents used regularly during catheter site care.

(I have reviewed data and in 263 cases paired BC was taken, results added in microbe pattern section. 48 cases were other source of infection, as this was not objective of study so we have not included it. All data reported is of tunnel line-temporary lines were excluded-mentioned in method section. Line salvaged was with IV abx)

 

The type of multivariable logistic regression should be described and cited rather than just mentioned in the methods section. Methods should be moved from results to methods.

(Done)

 

The discussion includes failure rates by organism species. Were these studies confirmed in this investigation e.g. Pseudomonas aeruginosa. Higher rates of infection in obese patients is well recognised with any device. The advice under conclusions echoes standard guidelines. More emphasis should be put on conclusions from this study. As a limitation the five hospitals used may not be applicable to hospitals in other countries or even others in the same country.

(Added new suggestion in conclusion section)

Reviewer 3 Report

Comments and Suggestions for Authors

Reviewer’s Report

 

General assessment

This manuscript addresses an important issue, namely bloodstream infections and subsequent vascular access loss in hemodialysis patients. The study is based on a multi-center, retrospective dataset over a 5-year period, which could provide valuable regional data. However, the manuscript suffers from major conceptual and methodological flaws that substantially undermine its validity and clarity. These issues cannot be adequately resolved by revision, and therefore I recommend rejection.

 

Major Concerns

1. Confusion between CRBSI and CLABSI

The manuscript uses the terms catheter-related bloodstream infection (CRBSI) and central line-associated bloodstream infection (CLABSI) interchangeably without clear definitions.

These are distinct epidemiological and clinical entities. If the authors intend to use them separately, proper definitions must be provided; if they mean the same, redundant terminology should be avoided. This lack of clarity affects the validity of the entire analysis.

 

2. Mismatch between objectives and study design

The stated objective is to assess the incidence and outcomes of CRBSIs, identify risk factors, and describe microbiological patterns.

Nevertheless, the dataset includes patients with AVFs and AVGs, in whom CRBSI or CLABSI by definition should not occur. Including these patients in multivariate analyses is conceptually incorrect and compromises the validity of the conclusions.

 

3. Patient selection and scope of inference

The study appears to include only patients with positive blood cultures. If so, it is not possible to analyze risk factors for infection incidence, since only infected patients were included. The analysis is limited to predictors of catheter removal after infection, but this distinction is not clearly described.

As a result, the conclusions regarding “risk factors for CRBSI incidence” are misleading.

 

4. Title is misleading

The manuscript focuses almost exclusively on central venous catheter (CVC) infections and their consequences. However, the title refers broadly to “vascular access loss,” which implies inclusion of AVF and AVG outcomes. This misrepresentation may confuse readers and overstates the scope of the study.

 

Minor Concerns

1. The introduction and methods contain redundant statements, which should be avoided.

2. In Table 1, variables with only Yes/No categories should be simplified by presenting only one.

3. In Table 2, “positive gram type” should be unified as “gram-positive” to match the terminology in the text.

4. The methods mention exclusion of temporary CVCs, but there is no clarification whether all catheters were cuffed tunneled catheters, which is essential information.

Author Response

General assessment

This manuscript addresses an important issue, namely bloodstream infections and subsequent vascular access loss in hemodialysis patients. The study is based on a multi-center, retrospective dataset over a 5-year period, which could provide valuable regional data. However, the manuscript suffers from major conceptual and methodological flaws that substantially undermine its validity and clarity. These issues cannot be adequately resolved by revision, and therefore I recommend rejection.

 Major Concerns

1. Confusion between CRBSI and CLABSI (Changed as suggested, CLABSI definition described)

The manuscript uses the terms catheter-related bloodstream infection (CRBSI) and central line-associated bloodstream infection (CLABSI) interchangeably without clear definitions.

These are distinct epidemiological and clinical entities. If the authors intend to use them separately, proper definitions must be provided; if they mean the same, redundant terminology should be avoided. This lack of clarity affects the validity of the entire analysis.

2. Mismatch between objectives and study design

The stated objective is to assess the incidence and outcomes of CRBSIs, identify risk factors, and describe microbiological patterns.(Objective was CLABSI but as other patients with AVF and AVG were there, we have reported that data)

Nevertheless, the dataset includes patients with AVFs and AVGs, in whom CRBSI or CLABSI by definition should not occur. Including these patients in multivariate analyses is conceptually incorrect and compromises the validity of the conclusions.(AVF and AVG patients were excluded from CLABSI rate, In BSI rate they are included)

3. Patient selection and scope of inference

The study appears to include only patients with positive blood cultures. If so, it is not possible to analyze risk factors for infection incidence, since only infected patients were included. The analysis is limited to predictors of catheter removal after infection, but this distinction is not clearly described.(We have included all positive blood cultures in our study and then further categorized those with tunnel lines)

As a result, the conclusions regarding “risk factors for CRBSI incidence” are misleading.

4. Title is misleading (Title Revised)

The manuscript focuses almost exclusively on central venous catheter (CVC) infections and their consequences. However, the title refers broadly to “vascular access loss,” which implies inclusion of AVF and AVG outcomes. This misrepresentation may confuse readers and overstates the scope of the study.

 Minor Concerns

1. The introduction and methods contain redundant statements, which should be avoided.(Corrected)
2. In Table 1, variables with only Yes/No categories should be simplified by presenting only one.(Done)
3. In Table 2, “positive gram type” should be unified as “gram-positive” to match the terminology in the text. (Done)
4. The methods mention exclusion of temporary CVCs, but there is no clarification whether all catheters were cuffed tunneled catheters, which is essential information.(Mentioned in method that temporary catheters were not included in study)

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

I did not find great improvement in your paper, and more than my previous suggestions were not followed. In addition, the reference Privitera et al., 2024, 10.1177/11297298241301508 is not present in your paper, even if it is strongly recommended and appropriate for your paper.

I hope you can consider my suggestions.

 

Author Response

Kindly find attached replies in the attached file.

Our hospital follows CDC for dialysis events calculation. I have attached it for reference regarding calculation of BSI and access rates.

I have attached CDC reference in supplementary file.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have revised according to suggestions

Author Response

There were no concerns from reviewer 2. All addressed in round 1.

Reviewer 3 Report

Comments and Suggestions for Authors

General assessment

The authors have revised the manuscript and addressed some of the earlier concerns. Terminology has been clarified, redundant expressions reduced, and table formatting improved. The title has also been refined to better reflect the focus on catheter-related infections. These are positive changes.

However, the issue pointed out in Major Point 3 last time remains unresolved: the study design does not allow for conclusions regarding the incidence or risk factors of CLABSI. The dataset consists of patients with positive blood cultures, not the entire dialysis population, and therefore the true denominator for incidence is unknown. This fundamentally limits the scope of inference. The study can provide insight into predictors of catheter removal once infection occurs, but it cannot validly estimate incidence or risk factors for infection occurrence.

 

1. Study scope and interpretation

 The manuscript still describes “incidence” and “risk factors for CLABSI,” but these cannot be derived from the present study design.

Since only infected patients were included, what can be assessed are factors associated with catheter removal after infection.

The conclusions must be reframed accordingly. Statements such as “The prevalence of CLABSIs in our facilities is highlighted” are inaccurate and misleading.

2. Clarity of objectives

 The stated objectives should be revised to match what the study can validly assess. For example, instead of “to determine incidence and risk factors for CLABSI,” the objective could be “to examine factors associated with catheter removal among hemodialysis patients with bloodstream infections.”

3. Conclusion

 The Conclusion section requires substantial rewriting to reflect the true scope of the findings.

 

The manuscript shows improvement in terminology and presentation. However, the central methodological concern—claiming incidence and risk factors when only infected patients were studied—remains unaddressed. The authors must substantially reframe the objectives, results, and conclusions to reflect what the study can actually demonstrate: risk factors for catheter removal following bloodstream infection.

Author Response

Attached pdf file for replies regarding comments from round 2.

I have attached CDC reference in supplementary file.

Author Response File: Author Response.pdf

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

Every suggestions were followed

Author Response

All suggestions have been followed in round 2. No new concerns mentioned.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors report the incidence rate of CLABSI; however, the Methods section does not clearly describe how this rate was calculated. It is strongly recommended that the definition and calculation method of the incidence rate be clearly described in the Methods section, including the denominator used (e.g., per 100 catheter-months or per 100 patient-months) and the rationale for this approach, to ensure clarity and reproducibility.

Author Response

Thanks for the feedback.

I have added the CDC formula for calculation of BSI and CLABSI (which we have used in our study).

I have re-written method with subheadings in order to give clear reproducibility.

Thanks