Extended-Spectrum Beta-Lactamases (ESBLs) Gene Mutations in Kuwait: How Much Do We Know? Not Much!
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe paper is a primary review of some publicly available data sources. in this current presentation as a review article, doent add any contents to current data. majority of the paper is about general data of ESBL definition. the last part is related to the focus of the paper meaning the approached frequency of ESBL in Kuwait. this part simply lists some papers published in Kuwait and doesn't discuss critically technical points and promising points to enrich the future in this field. to improve this focus of paper should be enriched and discuss more technical methods and results of data from kuwait. having some illumination demographically to compare with other regions could improve the paper well.
Author Response
Reply to Reviewer 1
We wish to thank the Reviewer for their time in reading our paper and for their valuable comments. We wish to kindly provide the following reply. We hope this would address the reviewer’s comments.
Comments and Suggestions for Authors
In our paper, we thought to take the reader in a journey to firstly clarify the problem of antibiotics resistance in general, then move to specifically focus on the ESBL, and finally reach to the problem of ESBL mutations in Kuwait. As we mentioned in the paper, we found a limited number of studies on ESBL in Kuwait; PubMed search revealed only 41 papers, and only 13 of them studied ESBL genetics in Kuwait over 17 years.
We agree with the reviewer that critical analysis of the results of these studies in Kuwait would have enriched the paper, and also to compare the results of Kuwait with other studies in the geographic region. However, that was not our aim of this paper. We only aimed to present the currently published data, aiming to show how limited is the number of the studies in Kuwait on this serious problem, and to emphasize on the necessity of conducting more studies to address this problem in Kuwait. Therefore, we briefly presented the results of these 13 publications (table 1) and touched base on some of the facts regarding their results. Frankly speaking, we were surprised by the small number of studies in Kuwait, which is a rich country with many research resources and facilities. We wish to ring an alarming bell and encourage more studies and collaboration among microbiologist in Kuwait to address this problem. Please be informed that we have re-written the last part of the paper to clarify more about our aim in this paper.
We think that it would be great to write future papers to analyze new data and results of future studies once they appear, and compare the results with other countries. We thank the reviewer for this valuable suggestion and for the whole review.
Reviewer 2 Report
Comments and Suggestions for AuthorsPlease see attached.
Comments for author File: 
Comments.pdf
Minor editinf of English Language is required.
Author Response
Reply to Reviewer 2
We wish to thank the Reviewer for their time in reading our paper and for their valuable comments. We wish to kindly provide the following reply. We hope this would address the reviewer’s comments.
Major comments:
In our paper, we only aimed to present the currently published data, aiming to show how limited was the number of the studies in Kuwait on this serious problem. We didn’t aim to present the mutations themselves. We agree with the reviewer that presenting and analyzing the results of these studies is important, but that was out of the main purpose of this paper. We only present some information in the table and text, but we tried to focus on “how limited the studies were in Kuwait, a country with many research resources and facilities, trying to ring an alarm and encourage more studies to be conducted on this serious problem”. Please be informed that we have re-written the last part of the paper to clarify more about our aim in this paper.
We think that it would be great to write future papers to analyze current and new data of future studies once they appear, and compare the results with other countries. We thank the reviewer for this valuable suggestion.
Line 198-224:
We added a subheading “Search strategy”, and a figure showing that as a flowchart (figure 3), as was suggested by the reviewer.
Line 200:
The date was added as requested: August 2024.
Table 1:
Genus and species names were Italicized in the table and throughout the manuscript.
Regarding showing the percentage of the ESBL genes in the table, we wish to mention again here the aim of our paper was to focus on the limited number of papers on ESBL in Kuwait, rather than the mutations themselves.
We think it would be great to write future papers to analyze current and new data of future studies on the different mutations and their percentages, and compare the results with other countries in the region and worldwide. We thank the reviewer for this valuable suggestion.
Line 240-242:
Sadly, it is a known fact in Kuwait that part of the sewage is discharge into the sea. This was also mentioned by the same article we are discussing in that paragraph (number 47). We added that reference to the end of the sentence. We also put the exact percentage of sewage being disposed of (25%).
Line 254:
We added 4 references on the “increase in ESBL-producing bacteria over the years” (references 48 to 51). For this, we added a few sentences towards the end of the manuscript, indicating these references. However, we did not put the reference numbers in the conclusion section itself since they were mentioned just a few lines before the conclusion.
Minor comments:
Line 16: The sentence was re-written.
Line 48: The sentence was modified.
Line 53: The word “ancient” was deleted, and the sentence was re-written
Line 55: The word “generations” was replaced by “types” to make it simpler.
Line 63: We added “horizontal gene transfer (HGT)” towards the end of the sentence.
Line 82: On our original submission to the journal, it was all written as “β-lactam”. It seems in the copy you got, the “β” was missing. May be due to conversion to PDF format by the journal.
Line 91: We changed the word “beta” into “β” everywhere in the manuscript, except when the full name of ESBL was mentioned, we kept as “Extended-spectrum beta-lactamases”.
Line 125, 126 130: Similar to what we said in line 82 above. It seems the “b” was lost in the copy that reached you. We had it in our original manuscript.
Line 180: Corrected.
Line 190-197: The whole paragraph was rephrased.
Line 226: The word “engine” was deleted.
Line233: The sentence was deleted and modified.
Author Response File: 
Author Response.docx
Reviewer 3 Report
Comments and Suggestions for AuthorsThe manuscript entitled „Extended-Spectrum Beta-Lactamases (ESBLs) Gene Mutations in Kuwait: How Much Do We Know? Not Much!” is a literature review manuscript. The topic of this manuscript is an important issue, however, some parts in the text should be revised.
Comments
1) The title does not fully cover the manuscript. The introduciont part is very long and very general data are presented: history, chemical structure of beta-lactams, mechanism of action, classification and genetics. All these are important, but it would be better in a more consice way.
2) What was the reason to choose only ESBL genes in Kuwait for this manuscript? In Pubmed there are high number of different articles available in the topic of carbapenem resistance and multidrug-resistance in Kuwait. I suggest to authors to give a broader view about antibitoic resistance in Kuwait.
3) I also suggest to describe possible associations between ESBL producing strains and carbapenem resistance, fluoroquinolone resistance, aminoglycoside resistance, and colistin resistance in Kuwait.
4) In my opinion a comparative analysis of resistance in Kuwait and in other countries could be also presented.
5) In Table 1 in the column of „ESBL genes reported” you present CMY-2, ACT but these are AmpC type beta-lactamases and not ESBLs. KPC is also presented here, but this is a carbapenemase, not an ESBL.
6) In Figure 3 you present again CMY-2, ACT but these are AmpC type beta-lactamases and not ESBLs. KPC is also presented here again, but this is a carbapenemase, not an ESBL
Author Response
Reply to Reviewer 3
We wish to thank the Reviewer for their time in reading our paper and for their valuable comments. We wish to kindly provide the following reply. We hope this would address the reviewer’s comments.
Comments
1) Regarding the title of the manuscript, we could change it to:
“A review on Extended-spectrum beta-lactamases (ESBLs) gene mutations, with a special focus on the situation in Kuwait: How much do we know? Not much!”
If the reviewer finds it more suitable, we can adopt it and inform the journal.
Regarding the length of the first part of the manuscript, we thought to take the reader in a journey to firstly clarify the problem of antibiotics resistance in general, then move to specifically focus on the ESBL, and finally reach to the main goal to present the problem of ESBL mutations in Kuwait. We agree with the reviewer that all these information are important.
2) We chose ESBL because it is of more interest to us and our research. We agree with the reviewer that the manuscript could be expanded to cover other antibiotics resistance cases, but our main aim was to present the currently published data, aiming to show how “limited” was the number of the studies in Kuwait on this serious problem. We didn’t aim to discuss the mutations themselves. We tried to focus on “how limited the studies were in Kuwait, a country with many research resources and facilities, trying to ring an alarm and encourage more studies to be conducted on this serious problem”. Please be informed that we have re-written the last part of the paper to clarify more about our aim in this paper.
We think it would be great to write future papers to analyze data on ESBLs and their mutations in Kuwait, and compare the results with other countries in the region and worldwide. We thank the reviewer for this valuable suggestion.
3) Also this is another valuable suggestion by the author, but as we said in number 2 above, our aim was different. Maybe if this paper is published, some researchers may be encouraged to write elaborated papers on different bacterial resistance cases in Kuwait, and compare with other countries.
4) The reviewer is right, but again it is not the aim of this paper. We really thank the reviewer for this valuable suggestion, and we hope to see it done in the future.
5 & 6) we agree with the reviewer that CMY-2, ACT and KPC are not ESBL. They were added because they were reported by the articles mentioned in the table and figure. We are sorry, we should have clarified that in the paper.
We added a note in the legends of the table and figure 4. We appreciate you mentioned this so we could correct it.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAfter careful evaluation of the paper i beilieve the ervisions didnt increase the sciebtific load of the paper regarding the comments.
the paper doesnt have any scietific impact, the message of authors is only that the studies in kuwait is not enough. there is not analysis of the results or even discussing the finding results of these studies in kuwait.
as the kuwait has a low population it wont be unexpected to have just few studies there. this is not matter of having enough facilities that authors claim on it. furtheremore as i commented before the majority of the paper is about general informations of antibiotics and resistance which can be easily googles and doesnt have any novelty. i was hoping in the section 8 authors minimum can expalin some results of the local studies but it is merely about two previous papers already published by authors. it is not a scientific review style and lack scientific gain for readers.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe revisions made to the manuscript significantly enhanced its clarity and depth. I congratulate the authors for their diligent work in addressing the feedback. I recommend that the manuscript be accepted for publication.
Reviewer 3 Report
Comments and Suggestions for AuthorsThis manuscript has been revised. All necessary modifications have been done in the text.
