Challenging fungal infections in cystic fibrosis: a case of mixed Aspergillus species infection and antifungal combination testing
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Aspergillus stands as the predominant fungal genus in the airways of cystic fibrosis (CF) patients, significantly contributing to their morbidity and mortality. Aspergillus fumigatus represents the primary causative species for infections, though the emergence of rare species within the Aspergillus section Fumigati has become noteworthy. Among these, Aspergillus lentulus is particularly significant due to its frequent misidentification and intrinsic resistance to azole antifungal agents. In the management of invasive aspergillosis and resistant infections, combination antifungal therapy has proven to be an effective approach. This report documents a case involving the death of a CF patient due to a pulmonary exacerbation linked to the colonization of multiple Aspergillus species, including A. lentulus , A. fumigatus , and A. terreus , and treated with Itraconazole (ITC) monotherapy. We delineated the procedures used to characterize the Aspergillus isolates in clinical settings and simulated in vitro the impact of the combination antifungal therapy on the isolates obtained from the patient. We evaluated three different combinations: Amphotericin B (AMB)+Voriconazole (VRC), AMB+Anidulafungin (AND), and VRC+AND. Notably, all strains isolated from the patient exhibited a significant decrease in their minimum inhibitory concentration (MIC) or minimum effective concentration (MEC) values when treated with all antifungal combinations. The VRC+AMB combination demonstrated the most synergistic effects. This case report emphasizes the critical importance of susceptibility testing and precise identification of Aspergillus species to enhance patient prognosis. It also underscores the potential benefits of combined antifungal treatment, which, in this case, could have led to a more favourable patient outcome.
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This is a study that would be of interest to the field and community.
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Comments to Author
Authors responses to my comments convinced for the accept descision.
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Thank you for addressing all concerns raised.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
This is my review report for the manuscript ID: ACMI-D-23-00234. This study is about a case of CF patient infected with respiratory Aspergillosis. The authors performed a several valuable antifungal susceptibility tests that I think will be more useful for the future clinical management of this status (CF + Aspergillus). The manuscript is well written. All standards of a case report (case description, therapy, and outcome) were applied. However, I prepared some minor/major comments and hope to improve the quality of the presentation. Comments * Kindly reduce the introduction section to less than one page. I think the authors should focus on Aspergillus spp rather than the bacterial species. Therefore lines 52 to 57 should be removed. * Line 74, 75: the authors said that "studies have demonstrated …
Comments to Author
This is my review report for the manuscript ID: ACMI-D-23-00234. This study is about a case of CF patient infected with respiratory Aspergillosis. The authors performed a several valuable antifungal susceptibility tests that I think will be more useful for the future clinical management of this status (CF + Aspergillus). The manuscript is well written. All standards of a case report (case description, therapy, and outcome) were applied. However, I prepared some minor/major comments and hope to improve the quality of the presentation. Comments * Kindly reduce the introduction section to less than one page. I think the authors should focus on Aspergillus spp rather than the bacterial species. Therefore lines 52 to 57 should be removed. * Line 74, 75: the authors said that "studies have demonstrated …." but they give one reference (ref #12). Kindly give more reference about this statement. * Kindly give the accession number of the βtubulin 2A/B genes sequence in line 99. * Why the authors didn't apply the molecular investigation for confirmation of the Aspergillus (LIF 3104)? * Kindly give three accession numbers for three identified isolates.
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
Methodological Rigour, Reproducibility, and Availability of Data: The methodologies for identifying Aspergillus species and testing antifungal combinations are detailed, providing a clear understanding of the procedures followed. However, the manuscript states that no new data were generated, which might raise concerns about the reproducibility of the research in a broader context. The availability of underlying or supporting data is not explicitly mentioned, which could be a limitation for those attempting to replicate or build upon this work. Presentation of Results: The results are well-presented with clear descriptions and effective use of visual aids like figures and tables. The case description and outcomes of antifungal combination testing are detailed, providing a comprehensive view of the …
Comments to Author
Methodological Rigour, Reproducibility, and Availability of Data: The methodologies for identifying Aspergillus species and testing antifungal combinations are detailed, providing a clear understanding of the procedures followed. However, the manuscript states that no new data were generated, which might raise concerns about the reproducibility of the research in a broader context. The availability of underlying or supporting data is not explicitly mentioned, which could be a limitation for those attempting to replicate or build upon this work. Presentation of Results: The results are well-presented with clear descriptions and effective use of visual aids like figures and tables. The case description and outcomes of antifungal combination testing are detailed, providing a comprehensive view of the study's findings. Style and Organization: The manuscript is logically structured, with a clear flow from introduction, case presentation, results, and discussion. The use of subheadings enhances readability, and the technical language is appropriate for a scientific audience. Literature Analysis or Discussion: The discussion section is well-developed, situating the findings within the broader context of cystic fibrosis treatment and fungal infections. The literature cited is relevant and current, supporting the arguments made in the discussion. The implications of the findings for future research and clinical practice are well articulated. Additional Comments: The case study approach adds value by providing a practical example, though it might limit the generalizability of the findings. The manuscript successfully highlights the importance of antifungal combination therapy in treating challenging cases of Aspergillus infections in cystic fibrosis. The paper would benefit from a clearer explanation of the reproducibility aspects and the availability of data for further research. Overall, the manuscript provides valuable insights into the treatment of fungal infections in cystic fibrosis and contributes meaningfully to the field. Enhancements in clarifying data availability and reproducibility aspects could further strengthen the paper.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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