Central Vascular Access Devices: Current Standards and Future Implications

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript presented for review titled “Central vascular access devices: current standards and future implications" provides a comprehensive review of Central Venous Access Devices (CVADs), focusing on Catheter-Related Bloodstream Infections (CRBSI). The authors explore CRBSI pathogenesis, patient, procedure, risk factors, preventive measures, and evidence-based strategies to mitigate CRBSI rates while discussing the impact of COVID-19 on infection rates.

The subject matter of this article is important as it emphasizes evidence-based algorithms adaptable to various healthcare settings to ensure scalability and resilience in infection prevention.

The systematic analysis of the topics raised by the Authors has been presented in a clear and coherent manner. The language of the work is understandable and easy to read. The manuscript is generally well written and clear.

However, this manuscript can be improved

Introduction

Authors should provide a section with a brief overview of CRBSI and CLABSI, emphasizing their diagnostic criteria and significance in epidemiological research as well adequate clarification or distinction. They should also in Introduction explain why these terms are frequently used as synonyms and discuss the implications this has for the review.

Providing more detailed data on infection trends across various healthcare settings and regions would also contribute to Introduction to be more focused and informative, setting a stronger foundation for the systemic analysis of the topic.

Methods

Authors should be more specific about inclusion/exclusion criteria. Were only peer-reviewed manuscripts included or conference abstracts, etc.

Was there any specific time frame for review (“last two decades” is broad term)? Why not older studies? Were all types of study designs in all languages included in the analysis?

Please specify search terms or filters you used when you were using PubMed, MEDLINE….

Definitions

Authors should provide a comprehensive comparison of CRBSI and CLABSI definitions by addressing the following: key diagnostic criteria (source of infection, clinical symptoms…), present situations where these definitions might diverge and highlight significance of adopting standardized definitions.

Results

Authors should add quantitative data like percentage or ratios (e.g. how much some intervention reduce CRBSI rates)?

Discussion

Authors should discuss the possible obstacles/challenges to adopting advanced technologies in low-resource settings.

Author Response

Comments by reviewer ONE:

The manuscript presented for review titled “Central vascular access devices: current standards and future implications" provides a comprehensive review of Central Venous Access Devices (CVADs), focusing on Catheter-Related Bloodstream Infections (CRBSI). The authors explore CRBSI pathogenesis, patient, procedure, risk factors, preventive measures, and evidence-based strategies to mitigate CRBSI rates while discussing the impact of COVID-19 on infection rates.

The subject matter of this article is important as it emphasizes evidence-based algorithms adaptable to various healthcare settings to ensure scalability and resilience in infection prevention.

The systematic analysis of the topics raised by the Authors has been presented in a clear and coherent manner. The language of the work is understandable and easy to read. The manuscript is generally well written and clear.

However, this manuscript can be improved

Introduction

Authors should provide a section with a brief overview of CRBSI and CLABSI, emphasizing their diagnostic criteria and significance in epidemiological research as well adequate clarification or distinction. They should also in Introduction explain why these terms are frequently used as synonyms and discuss the implications this has for the review.

Providing more detailed data on infection trends across various healthcare settings and regions would also contribute to Introduction to be more focused and informative, setting a stronger foundation for the systemic analysis of the topic.

Methods

Authors should be more specific about inclusion/exclusion criteria. Were only peer-reviewed manuscripts included or conference abstracts, etc.

Was there any specific time frame for review (“last two decades” is broad term)? Why not older studies? Were all types of study designs in all languages included in the analysis?

Please specify search terms or filters you used when you were using PubMed, MEDLINE….

Definitions

Authors should provide a comprehensive comparison of CRBSI and CLABSI definitions by addressing the following: key diagnostic criteria (source of infection, clinical symptoms…), present situations where these definitions might diverge and highlight significance of adopting standardized definitions.

Results

Authors should add quantitative data like percentage or ratios (e.g. how much some intervention reduce CRBSI rates)?

Discussion

Authors should discuss the possible obstacles/challenges to adopting advanced technologies in low-resource settings.

 

 

Dear Reviewer ONE,

We are deeply grateful for your thoughtful and constructive feedback on our manuscript titled “Central vascular access devices: current standards and future implications.” Your generous comments about the clarity, coherence, and significance of our work are greatly appreciated, and your detailed suggestions have been invaluable in refining the manuscript further.

We would like to address each of your comments with humility and gratitude:

Introduction:
Thank you for highlighting the need for a clearer distinction between CRBSI and CLABSI, as well as their significance in epidemiological research. We have now added a very brief overview of these terms, elaborating on their diagnostic criteria and addressing why they are often used synonymously. Furthermore, we have enriched the Introduction with more detailed data on infection trends across healthcare settings and regions to provide a focused and comprehensive background.

Methods:
Your recommendation to specify the inclusion/exclusion criteria and search strategy was insightful. We have now clarified that only manuscripts from peer-reviewed journals were included, while conference abstracts and other non-peer-reviewed sources were excluded. The review focused on studies published within the past two decades to prioritise the most relevant and current evidence, and excluded older studies. Additionally, we have provided further details on the search terms, filters, and databases (e.g., PubMed, MEDLINE) used, ensuring transparency and “reproducibility” of our methodology.

Definitions:
We completely agree that a comprehensive comparison of CRBSI and CLABSI definitions would strengthen the manuscript. In response, we have expanded this section to include key diagnostic criteria such as infection sources and clinical symptoms. We have also identified situations where these definitions may diverge and emphasised the importance of adopting standardised definitions to improve research comparability and clinical outcomes.

Results:
Thank you for your thoughtful comments and suggestion regarding the inclusion of quantitative data, such as percentages or ratios, in our review. We understand the importance of providing clear and measurable outcomes, especially when discussing the effectiveness of various preventative strategies for catheter-related bloodstream infections (CRBSIs). However, as we examined a range of studies from different settings within countries and across different countries, we encountered a significant variability in findings. For example, the use of antimicrobial locks was shown to reduce CRBSI rates from 10/1000 to 2/1000 catheter days in one study, while another reported a decrease from 2/1000 to 0/1000 catheter days. This variability in results prevents us from confidently stating a specific ratio or percentage that applies universally.

Given this inconsistency, we hope that you can appreciate our decision to focus on a broader discussion of the strategies explored, rather than specific quantitative outcomes. We believe that each of these strategies, such as antimicrobial locks, proper catheter insertion techniques, and infection control protocols, plays an important role in preventing CRBSIs, although the exact extent of their effectiveness in different settings remains uncertain (i.e., many study authors do not elaborate on whether specific bundles were employed beforehand or were only introduced during their observation).

As we emphasise in our review, well-trained staff remains crucial to the success of any intervention and cannot be substituted by technology alone.

We hope that this explanation clarifies our approach, and we kindly ask for your consideration in accepting this nuanced perspective.

Discussion:
Your recommendation to address challenges in adopting advanced technologies in low-resource settings was extremely valuable. We have now included a whole new section in the Discussion exploring these obstacles, highlighting issues such as cost, infrastructure, and training requirements, while proposing potential strategies to overcome these barriers.

Once again, we sincerely appreciate the time and effort you have dedicated to reviewing our work. Your insightful suggestions have been instrumental in enhancing the quality and depth of the manuscript. We are confident that these revisions address your concerns comprehensively and hope the improved manuscript meets your expectations.

With warm regards and gratitude

Baldauf, H. Bonnemeier, R. Cemin, J. Hummel and O. Assadian

Reviewer 2 Report

Comments and Suggestions for Authors

            This manuscript provides a review of the current commonly used strategies/protocols implemented to reduce central venous access device-related bloodstream infections, including strategies related to device placement and maintenance. Overall, this manuscript provides a good summary of important components that should be included in any central vascular access device protocol to enhance safety and reduce risk of adverse events, providing basic guidelines that will help shape essential elements of central vascular access device use in the clinical setting.

 

I have included the following comments and suggestions to help strengthen the manuscript:

 

Lines 38-39: While it is assumed to be common knowledge, especially for this audience, it might help emphasize and remind reviewers of the importance of everything that is discussed later in this paper if you provided a few brief examples in these opening sentences of the “various medical conditions” that central venous access devices are used for and how crucial they can be for medical management.

 

Lines 138-140: This sentence is a bit unclear – may need to be reworded.

 

Lines 163-166: The use of an observer to monitor the interventionalist is a great suggestion introduced here – it would be helpful to briefly clarify the function of the observer – is it solely to monitor that the interventionalist is correctly following the algorithm?

 

Lines 167-188: While it should be obvious to the reader from context, it might be helpful to explicitly explain the clinically-relevant distinction between the times when “Insertion Bundles” strategies and “Maintenance Bundles” strategies are applied and used.

 

Lines 214-217: A reference provided for the correlation between maximum sterile barrier and reduced incidence of CRBSI may strengthen this important point provided here for the audience.

 

Lines 228-230: Similarly, a reference here for the point that a compound with CHX in combination with alcohol is superior to for CRBSI would help strengthen this valuable point.

 

Line 252: It may help to clarify the meaning in the first sentence that “Antiseptic exit site treatment is outlined in all algorithms”. For example, is this intended to mean that all CVAD protocols reviewed tend to include protocol for antiseptic exit site treatment, or that all designed algorithms should include this?

 

Lines 265-270: This was an excellent point to make warning of the potential complacency that may come about from using antiseptic wound dressings. It was great to emphasize this in this paragraph!

 

Lines 283-289: Great point here about the effects of material, number and diameter of CVADs and relationship with CRBSIs. In addition to examples of the relative context of use of different material CVADs that were already included, as well as the great paragraph on relative risk of different types of CVADs that follows this one, is there any evidence in the literature indicating a great risk of infection with certain material?

 

Lines 354-357: This was another great point crucial for CVAD management and CRBSI risk management. Is there any information about at what amount of dwell time CRBSI risk really begins to significantly increase, or does the risk seem to just increase steadily over time starting right at time of insertion?

 

Lines 379-383: Are there any hypotheses as to what aspects of the strategies to reduce CRBSI incidence were most severely impacted by the COVID-19 pandemic leading to the setback described? Expanding on ideas of how the COVID-19 pandemic most severely affected these strategies in this discussion section may help the audience identify areas requiring the most attention to help reduce CRBSI risk during future challen

Author Response

Comments by reviewer TWO:

This manuscript provides a review of the current commonly used strategies/protocols implemented to reduce central venous access device-related bloodstream infections, including strategies related to device placement and maintenance. Overall, this manuscript provides a good summary of important components that should be included in any central vascular access device protocol to enhance safety and reduce risk of adverse events, providing basic guidelines that will help shape essential elements of central vascular access device use in the clinical setting.

 

I have included the following comments and suggestions to help strengthen the manuscript:

 

Lines 38-39: While it is assumed to be common knowledge, especially for this audience, it might help emphasize and remind reviewers of the importance of everything that is discussed later in this paper if you provided a few brief examples in these opening sentences of the “various medical conditions” that central venous access devices are used for and how crucial they can be for medical management.

 

Lines 138-140: This sentence is a bit unclear – may need to be reworded.

 

Lines 163-166: The use of an observer to monitor the interventionalist is a great suggestion introduced here – it would be helpful to briefly clarify the function of the observer – is it solely to monitor that the interventionalist is correctly following the algorithm?

 

Lines 167-188: While it should be obvious to the reader from context, it might be helpful to explicitly explain the clinically-relevant distinction between the times when “Insertion Bundles” strategies and “Maintenance Bundles” strategies are applied and used.

 

Lines 214-217: A reference provided for the correlation between maximum sterile barrier and reduced incidence of CRBSI may strengthen this important point provided here for the audience.

 

Lines 228-230: Similarly, a reference here for the point that a compound with CHX in combination with alcohol is superior to for CRBSI would help strengthen this valuable point.

 

Line 252: It may help to clarify the meaning in the first sentence that “Antiseptic exit site treatment is outlined in all algorithms”. For example, is this intended to mean that all CVAD protocols reviewed tend to include protocol for antiseptic exit site treatment, or that all designed algorithms should include this?

 

Lines 265-270: This was an excellent point to make warning of the potential complacency that may come about from using antiseptic wound dressings. It was great to emphasize this in this paragraph!

 

Lines 283-289: Great point here about the effects of material, number and diameter of CVADs and relationship with CRBSIs. In addition to examples of the relative context of use of different material CVADs that were already included, as well as the great paragraph on relative risk of different types of CVADs that follows this one, is there any evidence in the literature indicating a great risk of infection with certain material?

 

Lines 354-357: This was another great point crucial for CVAD management and CRBSI risk management. Is there any information about at what amount of dwell time CRBSI risk really begins to significantly increase, or does the risk seem to just increase steadily over time starting right at time of insertion?

 

Lines 379-383: Are there any hypotheses as to what aspects of the strategies to reduce CRBSI incidence were most severely impacted by the COVID-19 pandemic leading to the setback described? Expanding on ideas of how the COVID-19 pandemic most severely affected these strategies in this discussion section may help the audience identify areas requiring the most attention to help reduce CRBSI risk during future challenge

 

Answers to reviewer TWO:

Lines 38-39:
Thank you for this valuable suggestion. We agree that including specific examples of medical conditions where central venous access devices (CVADs) play a crucial role could enhance the introduction. We propose adding examples such as " CVADs play a critical role in the administration of chemotherapy for oncology patients, delivery of parenteral nutrition for individuals with intestinal failure, facilitation of long-term intravenous therapy, and are commonly utilized for hemodialysis." These examples will underscore their importance in modern clinical management and set the stage for the detailed discussions in the manuscript.

 

Lines 138-140:
We appreciate the feedback regarding clarity. We will rephrase the sentence to improve readability. The revised sentence will read: " When conditions conducive to colony-forming unit (CFU) growth are present within the lumen of a CVAD, the development of a contaminated biofilm becomes inevitable."

 

Lines 163-166:
Thank you for highlighting the role of the observer. To clarify, the observer’s primary function is indeed to monitor the interventionalist’s adherence to protocol steps, ensuring all components of the algorithm are followed correctly. We will amend this section to make this explicit and emphasize the observer's role in fostering accountability and immediate feedback: “An observer may be incorporated into the protocol, serving a sterile role to monitor the interventionalist's adherence to the procedure while offering additional assistance when an extra set of hands is required.”

 

Lines 167-188:
This is an excellent point. We will explicitly define the distinction between "Insertion Bundles" and "Maintenance Bundles." Specifically, we will note that " In general strategies are divided into Insertion Bundles, which are protocols focused on ensuring aseptic technique and minimizing contamination risk during the placement of CVADs, while Maintenance Bundles are strategies applied post-placement to uphold sterility, prevent device colonization, and manage ongoing use." This clarification will highlight their unique applications and relevance to different phases of CVAD management.

 

Lines 214-217:
Thank you for the suggestion to strengthen this point with a reference. We will include relevant literature form the CDC guidelines. which have demonstrated the efficacy of maximum sterile barriers in reducing catheter-related bloodstream infection (CRBSI) rates. Including these references will substantiate this critical recommendation.

 

Lines 228-230:
We agree that a supporting reference here will add rigor. Evidence such as that from Darouiche et al. (1999), comparing chlorhexidine-alcohol solutions to povidone-iodine, will be cited to reinforce the statement regarding the superior efficacy of chlorhexidine in combination with alcohol.

 

Line 252:
We acknowledge the need for clarity in this sentence. We will rephrase it to say, "Antiseptic exit site treatment should be a standard component in all CVAD protocols, emphasizing its critical role in reducing infection risks." This revision ensures the intended meaning is clear to readers.

 

Lines 265-270:
Thank you very much for recognizing the importance of this warning.

 

Lines 283-289:
This is a thoughtful suggestion. We have included one contemporary study highlighting differences in relation to PICC materials employed.

 

Lines 354-357:
We appreciate this important question. The literature indicates that CRBSI risk increases over time, but evidence suggests that the steepest rise occurs after two weeks of dwell time, particularly in non-tunneled catheters. We will cite a study by Milstone et al. (2013)

 

Lines 379-383:
Your suggestion to elaborate on the pandemic’s impact is well-taken. We will expand this section by discussing potential factors such as the reallocation of healthcare resources, staffing shortages, and disruptions in adherence to sterile protocols. For example, studies have indicated that increased workload and shortages of personal protective equipment may have contributed to setbacks in infection control practices during COVID-19. Including this discussion will help readers anticipate and address vulnerabilities during future healthcare crises.

 

Thank you for your insightful and constructive feedback. We are confident these revisions will enhance the clarity, scientific robustness, and clinical utility of the manuscript.

 

 

Reviewer 3 Report

Comments and Suggestions for Authors

The present paper aimed to review strategies for reducing the incidence of Catheter-Related Blood- stream Infections (CRBSI) and examines factors contributing to variations in reported rates across developed countries, highlighting the significant morbidity, mortality, and healthcare resource burden associated with CRBSI and evidence-backed preventive measures. The review underscores the need for algorithms adaptable to various healthcare settings and the scalability of infection prevention systems to ensure resilience.

A few changes are needed, as follows:

Considering that the review is focused on CVAD-related bloodstream infections and central line-associated bloodstream infections (CLABSI), this should be also reflected by the title.

Results, Hand Hygiene: Please mention also latex allergy.

No information related to hospital-acquired infections is provided. Please include!

Please provide future research directions!

Author Response

Comments by reviewer THREE:

The present paper aimed to review strategies for reducing the incidence of Catheter-Related Blood- stream Infections (CRBSI) and examines factors contributing to variations in reported rates across developed countries, highlighting the significant morbidity, mortality, and healthcare resource burden associated with CRBSI and evidence-backed preventive measures. The review underscores the need for algorithms adaptable to various healthcare settings and the scalability of infection prevention systems to ensure resilience.

A few changes are needed, as follows:

Considering that the review is focused on CVAD-related bloodstream infections and central line-associated bloodstream infections (CLABSI), this should be also reflected by the title.

Results, Hand Hygiene: Please mention also latex allergy.

No information related to hospital-acquired infections is provided. Please include!

Please provide future research directions!

 

Response to reviewer THREE:

Thank you very much for your thoughtful and constructive feedback. We greatly appreciate your insights, and we believe that addressing your comments will significantly enhance the quality and clarity of the review.

We will revise the title to more accurately reflect the focus on CVAD-related bloodstream infections and central line-associated bloodstream infections (CLABSI), as suggested. This adjustment will ensure greater alignment with the content and improve its clarity.

Regarding the section on hand hygiene, we will indeed include a discussion on latex allergy. This is an important consideration, particularly in the context of healthcare settings where latex-based gloves are commonly used, and it is essential to acknowledge the potential for allergic reactions that may impact compliance with infection control practices.

In response to your comment on hospital-acquired infections (HAIs), we expand the review’s introduction to provide relevant information about CRBSI in relation to HAIs.

Finally, we appreciate your suggestion to include future research directions.

 

Thank you once again for your invaluable feedback, and we will ensure that the revisions address these points comprehensively.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have revised the manuscript and accepted and corrected all the given suggestions. The revised manuscript titled "Central vascular access devices and infection: current standards and future implications" demonstrates significant scientific and clinical value. The authors have addressed all relevant aspects of the topic with clarity and methodological rigor.

The content is comprehensive, well-structured, and supported by robust evidence. The preventive strategies discussed are actionable and relevant, and the manuscript effectively highlights both current practices and areas for future research. Furthermore, the clarity of the writing and the logical flow of ideas ensure that it will be accessible to a broad readership. Overall, it is a well-written and valuable contribution to the field of infection prevention in CVAD use.

 

Author Response

Comments by Reviewer ONE, round TWO:

The authors have revised the manuscript and accepted and corrected all the given suggestions. The revised manuscript titled "Central vascular access devices and infection: current standards and future implications" demonstrates significant scientific and clinical value. The authors have addressed all relevant aspects of the topic with clarity and methodological rigor.

The content is comprehensive, well-structured, and supported by robust evidence. The preventive strategies discussed are actionable and relevant, and the manuscript effectively highlights both current practices and areas for future research. Furthermore, the clarity of the writing and the logical flow of ideas ensure that it will be accessible to a broad readership. Overall, it is a well-written and valuable contribution to the field of infection prevention in CVAD use.

REPLY:

Thank you very much for your thoughtful and detailed feedback on our revised manuscript titled "Central vascular access devices and infection: current standards and future implications." We deeply appreciate your kind words regarding the scientific and clinical value of our work.

We are truly grateful for your recognition of the clarity, comprehensiveness, and methodological rigor of our manuscript. Your comments about the actionable nature of the preventive strategies and the accessibility of the content to a broad readership mean a great deal to us.

Your guidance and constructive suggestions during the review process have undoubtedly strengthened our work, and we are sincerely thankful for your valuable contribution to this manuscript.

Please do not hesitate to reach out if there are any further considerations or clarifications needed.

With kind regards and best wishes,

B. Baldauf

Author Response File: Author Response.docx