Genetic Mechanisms of Antimicrobial Non-Susceptibility to Novel Fluoroquinolone Delafloxacin Among Bulgarian Clinical Isolates of Streptococcus agalactiae
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsEpidemiological study regarding GBS clinical strains resistant to the new fluoroquinolone delafloxacin.
The study presents relevant data for the field of bacterial resistance that can be helpful for the antibiotic guide for clinical use. I have some suggestions to improve the presentation of the work in terms of text and description, which are presented as comments in the attached PDF file. Otherwise, my main suggestion is for the addition of the non-resistant strains data, since the authors refer to them in the discussion and also for comparison with the relevance of findings regarding the resistant strains. They could be added as supplemental information/results.
Thank you.
Comments for author File: 
Comments.pdf
Author Response
Dear Reviewer, dear Editor,
Thank you very much for the helpful comments. We have corrected the manuscript accordingly. The changes were marked in red. Line numbers have been provided to facilitate corrections.
Sincerely
Ref.: Ms. No. cimb-3640375
Genetic mechanisms of antimicrobial non-susceptibility to novel fluoroquinolone delafloxacin among Bulgarian clinical isolates of Streptococcus agalactiae
Current Issues in Molecular Biology
Reviewer 1:
- Comments to the authors:
General comment: The study presents relevant data for the field of bacterial resistance that can be helpful for the antibiotic guide for clinical use. I have some suggestions to improve the presentation of the work in terms of text and description, which are presented as comments in the attached PDF file. Otherwise, my main suggestion is for the addition of the non-resistant strains data, since the authors refer to them in the discussion and also for comparison with the relevance of findings regarding the resistant strains. They could be added as supplemental information/results.
Answer: Thank you very much for the helpful comments. We have corrected the manuscript accordingly. The changes were marked in red. Line numbers have been provided to facilitate corrections localisation. In brackets prior to the answers of comments, the exact location of corrections is indicated. Supplementary Table S1 with additional information regarding studied strains has been added.
- Comments to the authors: I believe this sentence would be better used in the discussion session. Please, re-write the end of the abstract summarizing the findings and significance of the paper.
Answer: (Abstract; page number: 1; paragraph: 1; lines: 25-26). The text has been modified and indicated sentence has been moved in the discussion section (lines 249-251).
- Comments to the authors:
- This should be only one paragraph - Mechanisms of resistance to quinolones, including delafloxacin
- This paragraph about the advantages of using delafloxacin and general efficacy should come before the resistance paragraph
- When changing the order of the previous paragraph, the end of the resistance paragraph will have the perfect link for this one about GBS (mentioned on the last sentence of the resistance paragraph)
Answer: (Introduction; page 1-2; paragraph 3-4; lines: 42-79) The indicated text has been rearranged.
- Comments to the authors: Both sentenced lacking reference
Answer: (Introduction; page number: 2; paragraph: 5; line: 83-84) The reference has been added.
- Comments to the authors:
- Which tests were used?
- Which test was used to obtain this value?
Answer: (Materials and Methods and Results, pages 3 and 4, paragraphs: 8, respectively 3; lines: 146 and 166) The indicated information about statistical analysis (Fisher’s exact test) has been added.
- Comments to the authors:
- "(Fig. 2)" there is an additional dot, please review along the document.
- ‘cause’
- ‘gyrA’
Answer: The text has been reviewed.
- Comments to the authors: From which site was this strain that showed these two additional mutations?
Answer: (Results; page 5; paragraph: 4; lines: 176-177). The indicated information has been added.
- Comments to the authors: Please, clarify. Does it mean that even though not widely used in the clinic, the resistance was detected by in vitro methods? But were not the samples isolated from the clinic?
Answer: (Discussion; paragraph: 1; line: 194) The text has been modified.
- Comments to the authors: Are there other gene mutations described in the literature? If so, please, describe in the resistance section.
Answer: (Discussion: page 5; paragraph: 2: line 195) The text has been modified. The word ‘mainly’ has been removed. Initially, we aimed to describe the uncertain roles of other genes such as parE and gyrB; however, this information was relocated to the introduction section.
- Comments to the authors: In other parts of the text, the authors say the mutations in both enzymes also lead to resistance to delafloxacin. So how this highlights a higher resistance to other fluoroquinolones? Please, clarify
Answer: (Discussion; page 5; paragraph: 3; line 212-214) The text has been revised. We meant higher MIC values.
- Comments to the authors: All tested isolates or all tested resistant isolates ?
Answer: (Discussion; page 5; paragraph 2; line 200) The text has been corrected. We meant ‘resistant isolates’.
- Comments to the authors: Where is this data shown?
Answer: (Discussion; page 5; paragraph 2, lines: 202-204). The text has been reorganized to prevent any potential misunderstandings.
- Comments to the authors: This paragraph is not linked to the discussion, is not adding any information regarding the results found in the study.
Answer: The paragraph has been removed.
- Comments to the authors: On the 3rd line of the Results section the authors say they found one sample that showed high level of non-susceptibillity. Which "both" studies they are referring in this sentence?
Answer: (Discussion; page 5; paragraph 2; lines: 212-214). The text has been rearranged and modified.
- Comments to the authors: These data were not shown in the currently study.
Answer: The data has been included in supplementary Table S1: Distribution of serotypes among delafloxacin resistant and delafloxacin susceptible GBS isolates.
- Comments to the authors: How are the resistance rates of GBS to fluoroquinolones? This information mentioned here makes me question what is the importance of using a new fluoroquinolone for the treatment of an infection caused by a bacteria that doesnt present high resistance issues, is that true? If not, please, clarify this paragraph.
Answer: (Discussion, page: 6, paragraph: 5, lines: 226-234) The texted has been modified. Additional data of resistance rate has been added.
Reviewer 2 Report
Comments and Suggestions for AuthorsDear Authors,
Congratulations on your research.
The topic is of great importance, especially in this context of antibiotic resistance and selection of resistant bacterial strains.
I would like to ask the authors if they have made a comparison between the results obtained with delafloxacin and other fluoroquinolones or other groups of antibiotics?
Why do the authors think delafloxacin is a good choice in the treatment of streptococcal infections?
Thank you and good luck
Author Response
Dear Reviewer, dear Editor,
Thank you very much for the helpful comments. We have corrected the manuscript accordingly. The changes were marked in red. Line numbers have been provided to facilitate corrections.
Sincerely
Ref.: Ms. No. cimb-3640375
Genetic mechanisms of antimicrobial non-susceptibility to novel fluoroquinolone delafloxacin among Bulgarian clinical isolates of Streptococcus agalactiae
Current Issues in Molecular Biology
Reviewer 2:
General comment: Congratulations on your research. The topic is of great importance, especially in this context of antibiotic resistance and selection of resistant bacterial strains. I would like to ask the authors if they have made a comparison between the results obtained with delafloxacin and other fluoroquinolones or other groups of antibiotics? Why do the authors think delafloxacin is a good choice in the treatment of streptococcal infections?
Answer: Thank you very much for the helpful comments. We have corrected the manuscript accordingly. The changes were marked in red. Line numbers have been provided to facilitate corrections localisation.
The comparison between the results obtained with delafloxacin and other antibiotics has been included (Discussion, page 6, paragraph 5, lines 222-234).
New details concerning the treatment of other streptococci with delafloxacin have been included (Discussion, page 6, paragraph 6, lines 240-246).
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThanks for addressing my previous comments. The only two comments I have now are regarding the text. One is regarding the paragraph in the introduction; compared to the previous version, this paragraph seems to have been moved mistakenly. My second comment is just a sentence lacking one word in the discussion. Both of them are marked, and the authors can find them in the attached pdf file.
Thank you.
Comments for author File: Comments.pdf
Author Response
Ref.: Ms. No. cimb-3640375
Genetic mechanisms of antimicrobial non-susceptibility to novel fluoroquinolone delafloxacin among Bulgarian clinical isolates of Streptococcus agalactiae
Current Issues in Molecular Biology
Reviewer 1:
- Comments to the authors:
General comment: Thanks for addressing my previous comments. The only two comments I have now are regarding the text. One is regarding the paragraph in the introduction; compared to the previous version, this paragraph seems to have been moved mistakenly. My second comment is just a sentence lacking one word in the discussion. Both of them are marked, and the authors can find them in the attached pdf file.
Answer: We sincerely appreciate your valuable feedback. The manuscript has been revised accordingly. The changes were marked in red. In brackets prior to the answers of comments, the exact location of corrections is indicated.
- Comments to the authors: This should be a separated paragraph as it was before, maybe during the rearrangement of the introduction this was mistakenly moved
Answer: (Introduction; page: 2; paragraph: 3; lines: 43-51) The indicated text has been rearranged. Indeed, during the process of rearrangement, this paragraph was inadvertently displaced. Thank you.
- Comments to the authors: ‘is demonstrated to have a high activity.’
Answer: (Discussion; page: 6; paragraph: 6; line: 245) The text has been corrected.
Dear Reviewer,
Thank you very much for the helpful comments.
