Oral Fosfomycin Formulation in Bacterial Prostatitis: New Role for an Old Molecule-Brief Literature Review and Clinical Considerations
, Stefano Stracquadanio 1,*, Carlo Maria Bellanca 3, Egle Augello 3, Manuela Ceccarelli 2, Giuseppina Cantarella 3, Renato Bernardini 3,4, Giuseppe Nunnari 5 and Bruno Cacopardo 2
Round 1
Reviewer 1 Report
I have read with interest the manuscript submitted by Marino et al.
I have some comments to be addressed to improve the manuscript:
- please describe all abbreviations used in the abstract (ex. ESBL, E. coli)
- please consider fragmenting the longer phrases (such as the last one from the abstract), to have a clear and comprehensive text.
- the first time a bacteria is mentioned in the text, the full name should be written; the following mentions should use only the abbreviated term (ex. P. aeruginosa row 89 or S. aureus - rows 95, 179, etc.).
- when writing a bacteria like Klebsiella spp. - only the word Klebsiella must be italicized, the correct form is Klebsiella spp.
- row 112 - the correct enzyme is adenylate cyclase.
- row 121 - undo italic on the word "and"
- row 149 - 3 o 4?
- row 220 Bouiller et al.
- please uniformly use the citing system. Either by name et al. [x] or at the end of the phrase.
- row 237 - if it is about a single case, why then do you say multiple times that the patientS were treated? In addition, the citation should be included also at the end of the next paragraph, given the fact that you discuss the same study.
- it is not correct to say that a bacteria is ESBL. the microorganism produces ESBL.
- in the text, abbreviations should always be described at first mention (ex, cAMP, MIC, ATP, MRSA, ESLB- E.coli, etc.
- please adjust table 1. You did not write what the number before some of the bacterias means. We have to guess that it is about the number of isolates examined, but it should be presented clearly.
- I highly recommend the text editing by a native-speaking English person.
Author Response
Please describe all abbreviations used in the abstract (ex. ESBL, E. coli)
Reply: Thank you for your suggestion. We added an Abbreviation list at the end of the manuscript.
Please consider fragmenting the longer phrases (such as the last one from the abstract), to have a clear and comprehensive text.
Reply: We rephrase the sentences and made them more concise.
The first time a bacteria is mentioned in the text, the full name should be written; the following mentions should use only the abbreviated term (ex. P. aeruginosa row 89 or S. aureus - rows 95, 179, etc.).
Reply: We checked the manuscript fixing bacterial name as you suggested.
When writing a bacteria like Klebsiella spp. - only the word Klebsiella must be italicized, the correct form is Klebsiella spp.
Reply: We fixed the typos.
row 112 - the correct enzyme is adenylate cyclase.
Reply: We fixed the typo.
row 121 - undo italic on the word "and"
Reply: We fixed the typo.
row 149 - 3 o 4?
Reply: We fixed the typo.
row 220 Bouiller et al.
Reply: We fixed the typo.
Please uniformly use the citing system. Either by name et al. [x] or at the end of the phrase.
Reply: We checked the whole manuscript as you suggested. We put the reference at the end of the sentence to make it more complete.
row 237 - if it is about a single case, why then do you say multiple times that the patientS were treated? In addition, the citation should be included also at the end of the next paragraph, given the fact that you discuss the same study.
Reply: Thank you for your precision. We fixed the typos.
It is not correct to say that a bacteria is ESBL. the microorganism produces ESBL.
Reply: We agree with you and we fixed the expressions.
in the text, abbreviations should always be described at first mention (ex, cAMP, MIC, ATP, MRSA, ESLB- E.coli, etc.
Reply: Thank you for your suggestion. We added an Abbreviation list at the end of the manuscript.
please adjust table 1. You did not write what the number before some of the bacterias means. We have to guess that it is about the number of isolates examined, but it should be presented clearly.
Reply: Thank you for the help. We modified the table, as you suggested.
I highly recommend the text editing by a native-speaking English person.
Reply: Thank you for the suggestion. A mother tongue English colleague helped us improving the manuscript.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript "Oral fosfomycin formulation in bacterial prostatitis: new role for an old molecule. Brief literature review and clinical considerations" is well written, however, it requires some editorial corrections to make it more readable and interesting to the reader. Below, there are few comments that the authors may find useful:
1. Abstract, line 21: Please substitute "E.coli" with full name "Escherichia coli" because it is used for a first time in the manuscript there.
2. Citations in the whole manuscript: The format of the citation should be changed from ".[1]" to "[1]." (dot is misplaced).
3. Line 49: "Since long ago..." - Please be more specific and use more accurate information.
4. Section 2. Fosfomycin pharmoacology: In my opinion, it should be divided into subsections, such as: in vitro studies, in vivo studies and others.
5. Section 2 contains too many paragraphs that are too short (sometimes one sentence long). Please merge some paragraphs into bigger ones.
6. Please add a chemical formula of fosfomycin in a Figure.
7. It could be easier for the reader to visualize the processes described in the lines 67-80 if the authors provide some graphics or schemes.
8. Lines 83-97: Please provide information about MIC values.
9. Table 1: The table caption should be more informative. Please provide the reader with the broader description.
Generally, the manuscript is quite interesting but it needs to be completely rewritten and some visual materials have to be added to improve its quality.
Author Response
- Abstract, line 21: Please substitute "E.coli" with full name "Escherichia coli" because it is used for a first time in the manuscript there.
Reply: We fixed the name, as you suggested.
- Citations in the whole manuscript: The format of the citation should be changed from ".[1]" to "[1]." (dot is misplaced).
Reply: We fixed citation style, as you suggested.
- Line 49: "Since long ago..." - Please be more specific and use more accurate information.
Reply: We changed the sentence, as you suggested.
- Section 2. Fosfomycin pharmacology: In my opinion, it should be divided into subsections, such as: in vitro studies, in vivo studies and others.
Reply: Thank you for your precious advice. We divided the section in paragraphs according to the contents.
- Section 2 contains too many paragraphs that are too short (sometimes one sentence long). Please merge some paragraphs into bigger ones.
Reply: We divided the section in paragraphs and merged them.
- Please add a chemical formula of fosfomycin in a Figure.
Reply: Thank you for the suggestion. We added three original figures in order to make the paper more comprehensible and captivating.
- It could be easier for the reader to visualize the processes described in the lines 67-80 if the authors provide some graphics or schemes.
Reply: Thank you for the suggestion. We added three original figures in order to make the paper more comprehensible and captivating.
- Lines 83-97: Please provide information about MIC values.
Reply: We added MIC values, according to scientific literature.
- Table 1: The table caption should be more informative. Please provide the reader with the broader description.
Reply: Thank you for the precision. We modified table caption as you suggested.
Author Response File: Author Response.pdf
Reviewer 3 Report
The manuscript entitled „Oral fosfomycin formulation in bacterial prostatitis: new role for an old molecule. Brief literature review and clinical considerations” b Marino et al. „ aims to summarize the relevance of this antibiotic in a specific therapeutic indication affecting male patients. While the idea of the manuscript is solid, the execution is quite poor, therefore extensive revisions need to be done before the paper could be considered for publication.
Additionally, comprehensive language changes are also needed, therefore the inclusion of a professional copy-editor should be considered before moving on with the revisions.
Abstract: the abstract needs to be a comprehensive summary of the contents of the manuscript, therefore it should be extensively revised to fit this purpose
general: latin terms (in vitro, in vivo) should be in italics
please adhere to the general taxonomical guidelines for writing bacterial names
the sequence of topics and sentences is often confusing, as the authors return to some topics again and again
L36: 1-5-9%, worldwide.
L38: (NIH)
L40: E. coli is considered the main causative agent..
uncomplicated and complicated UTIs
…and Proteus spp. are also rising. Please consider including the recent work of Burian and colleagues on this topic, if you deem it relevant to the topic:
https://farmaciajournal.com/issue-articles/epidemiology-and-antibiotic-resistance-profile-of-bacterial-uropathogens-in-male-patients-a-10-year-retrospective-study/
„outbreak” and „novel” in discussing ESBLs is hardly appropriate
Please rephrase that the increasing prevalence of ESBLs in UTI-causing Enterobacterales is a serious issue.
could you provide some resistance /prevalence data here?
please provide clear definitions on the therapeutic consequences of ESBL-positivity
please use singular forms, instead of „antibiotics resistance”, „fluoroquinolones resistance” etc.
please clarify the difference between ESBL and carbapenem-resistance, and the possible mechanisms for the latter.
please refrain from using the term „germs”. instead use microorganisms or bacteria
L49: For a long time, fosfomycin…
Connective sentences between individual sections are missing and should be added.
from L57 and onward: is there a need for new paragraphs for each individual sentence? new paragraphs should be considered between different sections of information in each section
L62: the molecular structure of fosfomycin
is also commercialized. why is this relevant? any differences to the previously mentioned two formulations?
broad bactericidal activity
L68-70: please rephrase
when describing the mechanism of action of fosfomycin, the authors should provide a summary figure of this and include the chemical formula of fosfomycin also (it could serve as a graphical abstract also)
L78-80: although this is important information, this sentence just throws it into the manuscript. information on this should be extended
L81-82: more information on this should be provided
L107: allowed for the identification
a minor induction of the GlpT transport system
….are metalloenzymes beloning to the glyoxalase superfamily and inactivate fosfomycin…
L119-122: this section needs to be rephrased as it is hard to understand
use intrinsic instead of inherent resistance
please provide some pharmacovigilance data on the possible adverse events associated with fosfomycin use
L160: please correct the unit of measure
L167: one of the „tiniest”…this is not the appropriate way to describe a molecule, please rephrase
L173-175: please rephrase
L214: …due to the poor antibiotic penetration of
L213-259: this section is basically just a listing of the studies of different authors without any synthesis of data
what is „bacterial MIC”? its simply MIC
the overall visibility of Table 1. could be improved
L326: the meaning of MDR was not previously defined
Author Response
Abstract: the abstract needs to be a comprehensive summary of the contents of the manuscript, therefore it should be extensively revised to fit this purpose
Reply: We revised the abstract as you suggested.
general: latin terms (in vitro, in vivo) should be in italics
Reply: We fixed the style.
please adhere to the general taxonomical guidelines for writing bacterial names
Reply: We changed bacterial names in the whole manuscript.
the sequence of topics and sentences is often confusing, as the authors return to some topics again and again Reply: We divided the section 2 in paragraphs, added three original figures and rephrase some sentences, hoping the paper would be clear and would not be redundant.
L36: 1-5-9%, worldwide.
Reply: We fixed it.
L38: (NIH) ok
Reply: We added the abbreviation.
L40: E. coli is considered the main causative agent..
Reply: We changed the sentence.
uncomplicated and complicated UTIs
Reply: We changed the sentence.
…and Proteus spp. are also rising.
Reply: We changed the sentence.
Please consider including the recent work of Burian and colleagues on this topic, if you deem it relevant to the topic:
https://farmaciajournal.com/issue-articles/epidemiology-and-antibiotic-resistance-profile-of-bacterial-uropathogens-in-male-patients-a-10-year-retrospective-study/
Reply: Thank you for the precious suggestion. We read and added the paper you suggest in order to improve paper quality.
„outbreak” and „novel” in discussing ESBLs is hardly appropriate
Reply: we changed these terms.
Please rephrase that the increasing prevalence of ESBLs in UTI-causing Enterobacterales is a serious issue.
Reply: We rephrase the sentence as you suggested.
could you provide some resistance /prevalence data here?
Reply: we added the information you required.
please provide clear definitions on the therapeutic consequences of ESBL-positivity
Reply: We added what you suggested.
please use singular forms, instead of „antibiotics resistance”, „fluoroquinolones resistance” etc.
Reply: We changed what you suggested.
please clarify the difference between ESBL and carbapenem-resistance, and the possible mechanisms for the latter.
Reply: We added few lines about this topic.
please refrain from using the term „germs”. instead use microorganisms or bacteria
Reply: We changed what you suggested.
L49: For a long time, fosfomycin…
Reply: We changed the sentence as you suggested.
Connective sentences between individual sections are missing and should be added.
Reply: we tried our best to make the paper clear and understandable.
from L57 and onward: is there a need for new paragraphs for each individual sentence? new paragraphs should be considered between different sections of information in each section
Reply: We merged little paragraphs as you suggested.
L62: the molecular structure of fosfomycin
Reply: We changed the sentence as you suggested.
is also commercialized. why is this relevant? any differences to the previously mentioned two formulations? Reply: We added few words about iv fosfomycin to clarify, however this is not the purpose of this review.
broad bactericidal activity
Reply: We changed the sentence as you suggested.
L68-70: please rephrase
Reply: We rephrase the sentence as you suggested.
when describing the mechanism of action of fosfomycin, the authors should provide a summary figure of this and include the chemical formula of fosfomycin also (it could serve as a graphical abstract also)
Reply: Thank you for your suggestion. We added three original figures to better explain what you suggested.
L78-80: although this is important information, this sentence just throws it into the manuscript. information on this should be extended
Reply: We moved the sentence in another paragraph explaining the concept.
L81-82: more information on this should be provided
Reply: we added more information, as you suggested.
L107: allowed for the identification
Reply: We changed the sentence.
a minor induction of the GlpT transport system
Reply: We changed the sentence.
….are metalloenzymes belonging to the glyoxalase superfamily and inactivate fosfomycin…
Reply: We fixed the sentence as you suggested.
L119-122: this section needs to be rephrased as it is hard to understand
Reply: We rephrased the sentence as you suggested.
use intrinsic instead of inherent resistance
Reply: We changed the term.
please provide some pharmacovigilance data on the possible adverse events associated with fosfomycin use Reply: We added a paragraph about what you suggested, thank you for the help.
L160: please correct the unit of measure
Reply: We fixed it.
L167: one of the „tiniest”…this is not the appropriate way to describe a molecule, please rephrase
Reply: We rephrased the sentence as you suggested.
L173-175: please rephrase
Reply: We rephrased the sentence.
L214: …due to the poor antibiotic penetration of
Reply: We changed the sentence as you suggested.
L213-259: this section is basically just a listing of the studies of different authors without any synthesis of data
Reply: We added extra information about the studies described and comments to discuss the results.
what is „bacterial MIC”? its simply MIC
Reply: We changed it.
the overall visibility of Table 1. could be improved
Reply: We modified the table according to other reviewers.
L326: the meaning of MDR was not previously defined
Reply: We added the missing meaning.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Thank you for your prompt responses. Although I see an improvement in the manuscript, I have some other comments to be addressed.
row 21 - ESBL-producing. Also, describe what ESBL means. An abbreviation list at the end of the document does not replace the need to specify what each abbreviation means, at the first use in text.
italicize the word Enterobacterales in all the manuscript.
row 32- precious??
row 52-54 - please rephrase.
the word gram should not be written in capital letter, unless it`s at the beginning of the sentence.
row 224 - less than
row 330 - italicize E. coli
Denes described a patients?
row 341-347 - in which study?
Table 1 - you wrote - Pathogen (n°of isolates). Therefore, the number should be written between ( ).
Pay attention to the refferences. Not all of them are written correctly according to the mdpi format. For example, 3,5,9,12,14 etc. have the year written without bold.
row 502 - Science (80-. ). ?
Author Response
row 21 - ESBL-producing. Also, describe what ESBL means. An abbreviation list at the end of the document does not replace the need to specify what each abbreviation means, at the first use in text.
Reply: We changed the text as you suggested.
italicize the word Enterobacterales in all the manuscript.
Reply: We changed the text as you suggested.
row 32- precious??
Reply: Thank you for your advise. It was a typo, the correct term is "previous" and it has been fixed.
row 52-54 - please rephrase.
Reply: We rephrased the sentence. Thank you for your suggestion.
the word gram should not be written in capital letter, unless it`s at the beginning of the sentence.
Reply: We changed the term in the whole manuscript.
row 224 - less than
Reply: We fixed it.
row 330 - italicize E. coli
Reply: We fixed it.
Denes described a patients?
Reply: We rephrased the sentence.
row 341-347 - in which study?
Reply: We added the references at the end of the pointed sentence.
Table 1 - you wrote - Pathogen (n°of isolates). Therefore, the number should be written between ( ).
Reply: We changed the table as you suggested.
Pay attention to the refferences. Not all of them are written correctly according to the mdpi format. For example, 3,5,9,12,14 etc. have the year written without bold.
Reply: We fixed the reference list.
row 502 - Science (80-. ). ?
Reply: We added the missing data.
Once again we would like to thank the editor and the reviewers for the time they spent to improve our manuscript. We hope with the changes proposed the manuscript would be accepted in your valuable journal.
Kind regards,
The Authors
Reviewer 2 Report
Thank you for addressing all my comments. I have no further suggestions.
Author Response
Thank you for your precious and valuable time.
Reviewer 3 Report
The authors have adequately addressed most of my concerns regarding the manuscript, and have substantially improved the quality of the paper. Overall, the present version of the manuscript may be considered for publication.
Author Response
Thank you for your precious and valuable time.
