Outbreak of Ralstonia spp. and Burkholderia spp. Catheter-Related Bloodstream Infection in Hemodialysis Unit

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 The paper with the title << Outbreak of Ralstonia spp and Burkholderia spp catheter-re- lated bloodstream infection in hemodialysis unit>> is a well written paper.  The authors describe a serious problem regarding the central venous catheter’s (CVC) infection in hemodialysis patients. I think that this study provides valuable   information for the Nephrology community in order to perform rapid diagnosis in case of central catheter’s infection in hemodialysis patients .

 

Author Response

We sincerely thank the Reviewer for the words of appreciation he reserved for our work.

Reviewer 2 Report

Comments and Suggestions for Authors

·         The study presents an outbreak of catheter-related bloodstream infections caused by Ralstonia spp and Burkholderia spp within a hemodialysis unit. Their goal was to pinpoint where the contamination originated, treat promptly infected patients, and establish measures to enhance the safety of dialysis treatment and minimize the likelihood of further infections.

·         This topic holds significance in nephrology and infectious diseases, particularly due to its focus on rare pathogens that primarily affect immunocompromised patients. In the literature a few sporadic cases have been reported and only two outbreaks with Ralstonia bacteremias within hemodialysis units.

·         The study provides a comprehensive account of the steps taken to investigate the contamination source. Researchers introduced a disinfection protocol aimed at preventing future infections, alongside conducting a microbiological analysis of the biofilm extracted from plastic tubes utilized in the hemodialysis procedure.

·         It would have been interesting if the researchers had examined additional factors contributing to immunodeficiency beyond renal insufficiency in patients, given that these bacteria predominantly cause infections in immunocompromised individuals.

·         The discussion part effectively presents the main findings and outcomes of the study, highlighting the management of infected patients, the detection of bacteria in the dialysis system, and proactive measures preventing infections in hemodialysis units.

·         I consider the mentioned references appropriate.

·         Tables and figure contribute to the clear presentation of data and results. Data concerning the immunological status of the patients and their past medical history could have been also included.

Comments on the Quality of English Language

Only a few grammatical errors were detected.

Author Response

We thank the Reviewer for his suggestions that ameliorate our manuscript.

According to the suggestions:

- we provided a description of the additional factors contributing to immunodeficiency beyond end-stage kidney disease of patients who developed infection in our dialysis unit. This description can be found in the Results section, page 4, lines 138-146.

- we added in Table 1 the available data concerning the immunological risk factors of the patients including their past medical history. We apologize but the immunological data such as CD3+/CD4+ lymphocyte counts, serum IgG levels, etc. were not checked in our population of infected patients at the time of the outbreak.

- the paper has been revised by an English speaker colleague for the correction of the grammatical errors.

Reviewer 3 Report

Comments and Suggestions for Authors

1. In the abstract, unsure if the abbreviations used are appropriate for both organisms. Moreover, the first sentence states Ralstonia and Burkholderia broadly. Should probably add "species" here. 

2. In the abstract, specific date ranges should be included. To state "2021" is misleading. 

3. Be consistent with italicizing organisms. 

4. Perhaps this is implied in the manuscript, but what defines an outbreak? More specifically why did the authors define this as an outbreak? There is no discussion on what prompted the investigation.  

5. Why were lines retained for at least 6 days in all patients given that you suspected colonization of the CVCs? Was lock therapy attempted and unsuccessful? 

6. Does Table 3 suggest that all of these organisms were found, but only the two discussed were implicated in infection? 

7. The authors should expand on their current practices prior to the outbreak and discuss more about how this outbreak may have occurred (eg root-cause analysis). Moreover, could also comment on why current practices failed. This is critical to describe if calling this an outbreak.   

8. Should the supplementary tables at the bottom be excluded since they are already included in the manuscript? 

9. In the paragraph prior to the discussion, it is mentioned 11 of 37 had biofilms, but only 7 patients developed infection? Please clarify. 

10. Given the susceptibility differences, was any sequencing done to evaluate if these were the same isolates or different isolates? 

Comments on the Quality of English Language

Minor editing of the English language is needed. 

Author Response

We thank the Reviewer for his suggestions that ameliorate our manuscript.

Minor revisions

1) we added species to the name of the bacteria in the abstract, page 1, lines 21.

2) we specified the period: from 7 to 16 April 2021, in the abstract, page 1, lines 24.

3) we corrected all the names of the organisms and their abbreviations in italics.

4) we added in the Materials and Methods Section, page 2, lines 72-73 the follow sentence: “The identification of more cases of infection developing in few days in our population of hemodialyzed patients led us to define it an outbreak”. Consistently, we added the appropriate reference: Houlihan CF and Whitworth JA. Outbreak science: recent progress in the detection and response to outbreaks of infectious diseases, Clinical Medicine 2019. The reference numbers in the text and in the References Section have been updated.

Major revisions:

5) “Why were lines retained for at least 6 days in all patients given that you suspected colonization of the CVCs? Was lock therapy attempted and unsuccessful?”

We discussed the need to remove the colonized CVCs with infectious disease specialists. According with them, we decided to wait some days of targeted antibiotic therapy prior to remove the colonized CVCs to reduce the risk of contamination of the new one. During this period of time a lock therapy was adopted. 

6) Does Table 3 suggest that all of these organisms were found, but only the two discussed were implicated in infection?

In Table 3, we report all the organisms found in the biofilm of the loading plastic tubes. The organisms highlighted in bold are implicated in infection. We added this information in the legend of the Table 3.

7)“The authors should expand on their current practices prior to the outbreak and discuss more about how this outbreak may have occurred (eg root-cause analysis). Moreover, could also comment on why current practices failed. This is critical to describe if calling this an outbreak”.

After an in-depth discussion with infectious disease specialists and microbiologists of our hospital, we hypothesized that probably because of the changes of climate temperatures some bacteria such as RB and BB could proliferate in the water colonizing the loading plastic tubes. Subsequently, bacteria can spread into the blood and colonized CVCs. Thus, we speculated that a disinfection of the loading plastic tubes using an integrated system might reduce the risk. Prior the outbreak the loading plastic tubes were not disinfected because we disinfected the dialysis consoles and the water distribution lines separately.

8)“Should the supplementary tables at the bottom be excluded since they are already included in the manuscript?”

 We excluded the supplementary materials.

9) “In the paragraph prior to the discussion, it is mentioned 11 of 37 had biofilms, but only 7 patients developed infection? Please clarify”.

Based on our experience the presence of contaminated loading plastic tubes does not necessarily cause infection in dialyzed patients. We speculated that infection, in order to develop, need a CVC to allow the bacteria to colonize it and to proliferate. Consistently, no patients with arteriovenous fistula dialyzed with dialysis consoles connected with the infected LPT developed infection. In addition, only few patients with CVC who dialyzed with dialysis consoles connected with the infected LPT developed infection. Thus, we hypothesized that risk factors contributing to immunodeficiency beyond renal insufficiency might contribute to the infection. In Results section, page 4, lines 138-146 we provided a description of the additional factors contributing to immunodeficiency beyond end-stage kidney disease of patients who developed infection in our dialysis unit. We added in Table 1 the available data concerning the immunological risk factors of the patients including their past medical history.

10) “Given the susceptibility differences, was any sequencing done to evaluate if these were the same isolates or different isolates?”

No sequencing was performed, since based on MICs the strain isolated from patient No. 5 differed in only one dilution from strains isolated from patients #1, #2 and #4. This suggests that the phenotype is the same. The same applies to isolates of patients #3 and #7.

The paper has been revised by an English speaker colleague for the correction of the grammatical errors.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have adequately addressed my comments. 

Author Response

Academic Editor Notes: The authors sorted out almost all the criticisms of the reviewers, however they should better clarify the daily doses and the duration of the different antibiotic used (for how many days the treatments lasted )

We sincerely thank the Academic Editor for his suggestions. We shifted the data regarding the antibiotic therapy from the Results section to the Materials and Methods Section (page 2, line 81 to page 3, line 85) adding the daily doses and the duration of the antibiotic therapies.