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Both reviewers agreed that the required revisions had been made. Although one reviewer expressed some doubts over the quality of the English, I thought it read clearly, and am happy to accept the manuscript with any further adjustments.
[# PeerJ Staff Note - this decision was reviewed and approved by Konstantinos Kormas, a PeerJ Section Editor covering this Section #]
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In the revised manuscript, the authors have adequately addressed my concerns, reaching the publication standards of PeerJ. However, before the manuscript can be formally published, a comprehensive improvement of the English language is required.
The authors have given a comprehensive account of Linezolid's in vitro antibacterial activity against unconventional pathogens such as M. tuberculosis, NTM, Nocardia, Corynebacterium striatum, anaerobes and fungi. This review clearly summarizes Linezolid's activity against pathogens other than its intended target group of Gram-positive bacteria and is an informative addition to the existing reviews on Linezolid and its antibacterial activity.
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The authors have incorporated all the necessary revisions in the manuscript suggested earlier.
Two of the reviewers felt that this was an interesting and comprehensive review, but still expressed various concerns and have suggested improvements. I'm confident that these will lead to a stronger manuscript.
The review manuscript is of interest to both microbiologists and clinicians working with off-label uses of antibiotics. It aligns with the journal's aim of promoting the dissemination of robust scientific data with cross-disciplinary applications.The manuscript provides a thorough background on the antimicrobial activity of linezolid beyond its primary indications. The references are comprehensive, recent, and relevant, covering both foundational and the latest studies (e.g., Mycobacterium tuberculosis and drug-resistant strains). The manuscript follows a professional structure, including clear sections (introduction, methodology, findings, etc.). Tables summarizing the antimicrobial activity across different pathogens are detailed and helpful. However, it would be beneficial to ensure that all figures and tables are referenced clearly in the text. Ensure proper alignment between the content and the figures (e.g., referencing the right data columns). The manuscript is generally well-written in professional English, but a few sentences require minor grammatical adjustments to improve clarity.
Aims and Scope
The study aligns well with the journal's scope and aims. The focus on unconventional pathogens is timely, especially with increasing antibiotic resistance.
Methodology
The literature search methodology is adequately described, including databases used (e.g., PubMed, Cochrane, MEDLINE) and search terms. The inclusion of papers from 1999 to 2023 ensures a comprehensive review.
Minor suggestion: Clarify the criteria for selecting studies (e.g., were any specific exclusion criteria used?). This would improve transparency and replicability.
Coverage and Citations
The cited studies are quoted and paraphrased appropriately, with no apparent signs of bias.
Logical Organization
The manuscript flows logically, with subsections focusing on different pathogen groups (e.g., NTM, Nocardia, anaerobes). This organization improves readability and ensures clarity.
Consistency with the Introduction and Goals
The review supports its objectives by thoroughly analyzing the antimicrobial spectrum of linezolid. It presents comprehensive MIC data across multiple studies and geographical regions.
Conclusions
The conclusions align well with the data presented, emphasizing the potential of linezolid in treating unconventional pathogens and the need for further research.
The discussion on antibiotic resistance and the emergence of resistant strains (e.g., linezolid-resistant tuberculosis) adds depth to the manuscript.
Unresolved Questions and Future Directions
While the review identifies gaps (e.g., limited clinical studies for certain pathogens), it would benefit from a dedicated section explicitly outlining future research priorities.
This manuscript offers valuable insights into the expanded applications of linezolid and fits well within the scope of PeerJ. With some minor revisions, it will be more rigorous and academically impactful.
1. The manuscript summarizes data from various studies but lacks a critical discussion of conflicting findings or study limitations.
Suggestion:
Add sections comparing the effectiveness of linezolid across different studies, highlighting inconsistencies or gaps (e.g., differences in MIC values across regions). Discuss any controversies or limitations in the literature, such as variations in methodology or sample sizes, and propose possible explanations.
2. Although the paper mentions off-label applications and potential therapeutic use, it does not sufficiently discuss the clinical implications, such as challenges in using linezolid for resistant pathogens or potential side effects.
Suggestion:
Include a more detailed discussion on the clinical limitations of using linezolid off-label, such as the risks of toxicity (e.g., myelosuppression, optic neuropathy) and resistance development. Propose when linezolid should be considered as an alternative or last-resort treatment based on the literature.
3. The manuscript provides a descriptive summary of in vitro studies but does not clearly identify specific research gaps or unresolved questions that future studies should address.
Suggestion:
Add a section in the conclusion or discussion explicitly identifying gaps in the current knowledge. For example, mention the need for in vivo studies, clinical trials, or comparative studies with other antibiotics. This will strengthen the relevance and academic impact of the review.
4. The methodology for the literature review is described briefly, but there is limited information on inclusion and exclusion criteria, search filters (e.g., language, publication type), or how duplicate studies were handled. This can affect reproducibility.
Suggestion:
Provide more detailed information on the review methodology, such as:
How were studies selected or excluded?
Were non-English papers or preprints included?
Were systematic reviews excluded to avoid duplication of data?
5. While the manuscript mentions linezolid resistance (e.g., in Mycobacterium tuberculosis and Nocardia), it does not provide a deeper analysis of the mechanisms or clinical strategies to address resistance.
Suggestion:
Expand the discussion of resistance mechanisms, such as mutations in the 23S rRNA gene and their clinical implications. Additionally, discuss potential ways to mitigate resistance, such as combination therapies or monitoring programs.
6. The data on MIC ranges and susceptibility are scattered across multiple sections. This makes it difficult for readers to quickly compare the activity of linezolid against different pathogens.
Suggestion:
Consider organizing data more effectively, perhaps by adding comparative tables summarizing MIC ranges for different pathogens. This will enhance readability and allow for quick cross-referencing.
7. Some sections reference multiple studies without clearly distinguishing their specific contributions or results. This can confuse readers.
Suggestion:
Use specific in-text citations to attribute data accurately. For example: “Yang et al. (2018) reported MIC values of 0.125-2 µg/mL, while Ahmed et al. (2013) found...” This will ensure clarity in the interpretation of the literature.
8. Although the paper concludes that linezolid has potential for expanded use, it lacks specific recommendations for future research directions.
Suggestion:
Provide concrete suggestions for future studies, such as:
Conducting clinical trials to evaluate the efficacy of linezolid against resistant NTM strains.
Exploring synergistic effects with other antibiotics in treating fungal or anaerobic infections.
Investigating biomarkers to monitor early resistance development.
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The author has made a commendable effort; however, numerous reports on Linezolid are already available in the literature, and this review article does not significantly contribute to the existing body of work. Larger studies from other regions, such as those addressing Pythium and Tuberculosis in India, should be included. Additionally, the article contains several grammatical errors that need correction.
The authors have given a comprehensive account of Linezolid's in vitro antibacterial activity against unconventional pathogens such as M. tuberculosis, NTM, Nocardia, Corynebacterium striatum, anaerobes and fungi. This review clearly summarizes Linezolid's activity against pathogens other than its intended target group of Gram-positive bacteria and is an informative addition to the existing reviews on Linezolid and its antibacterial activity.
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The manuscript does not contain Line numbers so it is difficult to mention specific mistakes in different sections. However, the language and formatting of the text need to be thoroughly rechecked. Following are some suggested improvements:
1. There are spelling errors such as 'especial' instead of 'especially'; 'Findings' instead of 'foundings';
'expanding use' instead of 'expending use' etc.
2. 'Anaerobes' should be written everywhere in the text instead of 'anaerobe'
3. G+ should be written as Gram-positive
4. In vitro and in vivo in italics
5. All bacteria names should be in italics
6. RGM is 'rapidly growing Mycobacterium' and not 'fast growing Mycobacterium' as written in text
7. The genus of bacteria should start with a capital letter and species and subspecies should start with a small letter
8. Text is not correctly formatted as specified by the journal.
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