Aspergillus otitis externa with persistent tympanic membrane perforation in a young immunocompetent patient

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Abstract

Herein a case of left ear Aspergillus otitis externa with associated persistent tympanic membrane perforation requiring tympanoplasty in an immunocompetent 28-year-old woman is described. Aspergillus otitis externa is uncommon in young immunocompetent patients lacking obvious risk factors. This clinical case highlights the importance of considering Aspergillus in the differential diagnosis of all patients presenting with otalgia and otorrhea that do not improve with antibiotic therapy to avoid complications from untreated otomycosis.

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  1. Thank you for submitting the revised version of your manuscript and for the detailed point-by-point response to the reviewers. I have carefully reviewed the revised submission alongside the reviewer comments and your responses. Overall, I am pleased to see the substantial effort undertaken to address the reviewers’ concerns. The revisions demonstrate careful engagement with the feedback, including improved clarity of the clinical timeline, clearer articulation of the educational focus of the case, refinement of claims regarding novelty, expansion of microbiological and diagnostic detail, and thoughtful discussion of clinical decision-making and stewardship issues. The manuscript has clearly benefited from these revisions, and I would like to acknowledge the considerable work the authors have invested in strengthening the paper. In my assessment, the authors have addressed the reviewer comments adequately, and the manuscript is now suitable for acceptance pending only very minor and more technical amendments. I am therefore issuing a minor revision, limited to the following points: • Table 1 correction There remains an inconsistency in Table 1 regarding treatment details. The table still lists triamcinolone IM, whereas both the response to reviewers and the revised manuscript text clarify that triamcinolone was administered as topical drops. Please correct Table 1 to ensure consistency throughout the manuscript. • References cited in Table 2 I appreciate the authors’ effort to remain within the journal’s stated reference limit. However, references cited within tables should be fully represented in the reference list for completeness and transparency. Please therefore include the references cited in Table 2 in the main reference list, even if this results in exceeding the nominal 30-reference limit. This will not negatively affect editorial consideration. These amendments are purely technical and do not require further scientific revision. Once these changes are made, the manuscript will be ready for final acceptance. I would like again to thank the authors for their careful revisions and for the constructive way in which they have engaged with the peer-review process.

  2. Comments to Author

    This research manuscript by Hathaway et al., manuscript ID; ACMI-D-25-00129R1, entitled "Aspergillus otitis externa with persistent tympanic membrane perforation in a young immunocompetent patient" report documents a 28-year-old immunocompetent female with Aspergillus otitis externa complicated by a persistent tympanic membrane perforation requiring tympanoplasty. The manuscript addresses a clinically important topic -delayed diagnosis of fungal otitis externa- and presents a reasonably detailed longitudinal clinical course. However, major revisions are required before consideration for publication. The work suffers from critical methodological limitations, unsupported claims of novelty, unacceptable figure quality, and missed opportunities for deeper clinical analysis. Below are my detailed comments and recommendations. * Firsly, the manuscript needs to be carefully edited for style, grammar, and clarity. There are multiple instances of grammatical errors and awkward wording. * The claim of a uniquely rare case is overstated. The cited incidence (5.5% persistent perforation) suggests it is uncommon, not exceptionally rare. The supporting literature review lacks systematic methodology. To substantiate novelty, a systematic review or a complete table of comparable cases is required; otherwise, the impact is overstated. * The diagnostic algorithm (Fig. 2) is unacceptable, being blurry, pixelated, and unreadable. All figures must be publication-quality. This figure must be redrawn professionally as a high-resolution vector graphic or flowchart with clear decision nodes and legible text to meet minimum standards. * The proposed pathophysiology (Tympanic membrane perforation) is logically inconsistent, first suggesting bacterial otitis led to secondary fungal colonization, then that Aspergillus was the primary, sole etiology. This is a critical distinction. If primary, it is exceptionally rare and requires expanded discussion. If secondary, the case's uniqueness is reduced. The authors must clarify the timeline with evidence and acknowledge any diagnostic uncertainty. * The microbiological workup for this Aspergillus-centric case is critically incomplete. It lacks: 1-Speciation, essential for linking morphology (e.g., black discharge) to a specific species complex. 2-Antifungal susceptibility data, weakening the treatment rationale. 3- Direct microscopic evidence (e.g., KOH, calcofluor white). Without speciation, claims about discharge color are unsubstantiated. This constitutes a major methodological limitation that severely undermines the report's scientific validity and must be addressed. * Several treatment decisions require explicit discussion and critique: (A frank discussion of these points is essential for the manuscript's educational value.)  The use of intramuscular triamcinolone (Day +10) is non-standard for otitis media; its rationale is absent, and its immunomodulatory effect may have promoted fungal proliferation.  The significant delay in obtaining cultures (Day +31) represents a suboptimal care pathway that should be highlighted as a critical learning point.  The multiple, overlapping antibiotic courses likely exacerbated fungal dysbiosis. The manuscript must critically analyze this iatrogenic factor rather than merely describing the treatments. * The patient's immunocompetent status is asserted based solely on history, lacking laboratory confirmation (e.g., CBC/differential, immunoglobulin levels, HbA1c). For a case report claiming rarity in this population, this constitutes a significant oversight. The manuscript must either provide baseline immunologic data or explicitly state this workup was not performed, with justification. * The identification of the pathogen only to the genus level ("Aspergillus spp.") represents a critical methodological flaw. Species within this genus (e.g., A. fumigatus, A. niger, A. flavus) differ significantly in virulence, antifungal susceptibility, and clinical presentation. Specifically, the observed black discharge is a hallmark of section Nigri (e.g., A. niger), but this cannot be correlated without speciation. Furthermore, the absence of antifungal susceptibility testing weakens the treatment rationale. Species-level identification via MALDI-TOF or sequencing is standard of care for a definitive diagnosis. The authors must either provide this data or justify its absence, as this omission substantially limits the case's scientific and educational value. * Table 1 cites several sources that are not included in the manuscript's reference list. All references cited within the manuscript, including those in tables and figure legends, must be present in the reference list. Please ensure the list is complete and accurate. * To improve clarity, I recommend including a graphical timeline summarizing the patient's clinical course. This should illustrate key milestones, interventions, and outcomes, providing readers with an immediate understanding of the case progression and the sequence of diagnostic and therapeutic actions. Herein are some comments to improve the manuscript: Abstract * To strengthen the clinical impact, it is recommended to explicitly highlight the 40-day delay to diagnosis as a key point in the discussion. This emphasizes a critical learning objective regarding the need for timely and targeted microbiological investigation in persistent otitis. Introduction * Please provides good background but should explicitly state the knowledge gap: specifically how often Aspergillus otitis externa presents without classic risk factors in immunocompetent patients and the true incidence of persistent TM perforation. Case Report * The administration of a systemic steroid (triamcinolone) on Day +10 requires explicit clinical justification. The rationale for this non-standard intervention in a case of suspected otitis media is absent. Please clarify the reasoning, as this decision may have influenced the subsequent clinical course and fungal proliferation. Discussion * The section on bacterial-fungal antagonism is interesting but speculative without microbiome data. Either provide references or temper the claims. * The statement "This perforation likely provided a moist environment... allowing Aspergillus growth" contradicts the earlier implication that Aspergillus caused the perforation. Resolve this tension. Conclusion * The manuscript overstates the case's novelty. Its primary contribution is not uniqueness, but its demonstration of a critical clinical lesson: a delayed fungal culture can lead to prolonged morbidity and potential irreversible complications, even in immunocompetent patients. Reframing the focus accordingly would significantly strengthen the paper's educational value. Table 1 * If included, the table must be complete, provide study designs (case series vs. reports), and include a column for persistent perforation duration. The current placeholder is insufficient. * Table 1 provides a valuable descriptive summary of the literature. To maximize its impact, a quantitative synthesis is recommended. Where the data allows, a simple pooled analysis (e.g., calculating the pooled prevalence of persistent TM perforation in immunocompetent versus immunocompromised cohorts) would significantly strengthen the comparative conclusions. Figure 1 * The TM perforation image is adequate but suboptimal. A labeled otoscopic view before surgery would be more valuable than an intraoperative photo. The current image shows little diagnostic detail.

    Please rate the quality of the presentation and structure of the manuscript

    Poor

    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

  3. Comments to Author

    Description of the case: Its a Well-described case of Aspergillus otitis externa with persistent tympanic membrane perforation in immunocompetent patient with detailed symptom progression and therapeutic regimens which offer valuable clinical insight. A summarized clinical timeline table could improve clarity and impact. Expand microscopic details on specimen collection, culture, and fungal identification for better diagnostic clarity and data on Aspergillus speciation and antifungal susceptibility testing is lacking, which is important in microbiology as far as the diagnosis is concerened. Presentatipon of results: Results are presented chronologically, which may hinder reader engagement.Use tables or timelines to communicate microbiological results, clinical findings, and therapy responses. Photographic or microscopic photographs of fungal culture or tissue enhance results and support diagnostic claims.The work has a standard structure, but the Introduction and Discussion sections are lengthy and masking crucial messages.A clearer division between background, case presentation, and discussion would enhance focus.Emphasize microbiological and clinical teaching aspects in the Abstract, Introduction, and Conclusion. Style and Oeganization of paper:The discussion frames the case within Aspergillus otitis externa and immunological risk factors studies. The study summarizes current knowledge on bacterial-fungal dynamics, antibiotic effects, and otomycosis consequences so consider organizing the conversation to emphasize clinical microbiology, antifungal management, and laboratory diagnostic problems. Few lines on new diagnostic technology and antimicrobial stewardship can be included. Clear microbiological procedures, including culture media, incubation conditions, and fungal stain used should be included.Clarify ethical aspects including patient consent and confidentiality.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    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

  4. Comments to Author

    The manuscript presents a case of Aspergillus otitis externa with a persistent tympanic membrane (TM) perforation in a young immunocompetent patient, highlighting an uncommon presentation of fungal otitis externa and its clinical challenges. The topic is relevant and potentially valuable to clinicians managing otologic infections, particularly those in tropical or subtropical climates where fungal infections are more prevalent. However, several areas require clarification and strengthening to improve the manuscript's clinical and scientific impact. 1. The authors claim that this presentation is rare in immunocompetent individuals. Please provide a more detailed review of existing literature to justify the uniqueness of this case. How many similar cases have been reported in immunocompetent patients, and what distinguishes this case? 2.The manuscript lacks detail regarding how the diagnosis of Aspergillus otitis externa was confirmed. Was microscopy, culture, or PCR performed? Were other fungal or bacterial co-infections ruled out? Information on the fungal species (e.g., A. niger, A. fumigatus) should be included, as treatment response may vary. 3.Please elaborate on the treatment protocol used—topical/systemic antifungals, duration of therapy, and patient adherence. If ototopical agents were used, clarify whether any ototoxic agents were involved, particularly given the tympanic membrane perforation. 4.The persistence of the tympanic membrane perforation is clinically significant. Did the authors consider surgical repair or follow-up audiological assessment? What was the timeline of follow-up, and were there any signs of chronic suppurative otitis media? 5.Although the patient is described as immunocompetent, a brief note on whether any basic immunological work-up was done (e.g., CBC, HIV, diabetes screening) would strengthen the case and confirm the immunocompetence. 6.The images provided (if any) should be high-resolution and include annotations if applicable. 7. Grammar and language should be reviewed for clarity and conciseness. Several sentences are overly long or ambiguous. The details comments are as below : Line 40: Skin infection occurs not only by systemic dissemination. Primary cutaneous aspergillosis occurs by direct inoculation of Aspergillus spores into the wounds Line 41-42: Mention about Aspergillus otitis externa in immunocompromised persons with references. Line 52-55: Please rewrite the sentence Line 57-58: Provide references Line 58-62: Provide references for bacterial agents and Candida Line 67-69: Please provide references Line 72-75: The sentence is complex Line 85-86: Mention the period from when the patient was suffering with diseases. Line 89-90: Whether the etiological agent of the recurrent otitis media identified at that time? It will be useful for the readers if pure medical terminology can be explained. Line 115-117: How could fungal debris be identified only on day +40? How was the sample collected? Was the sample a fluid or an ear swab? How was it cultured? Whether both bacterial and fungal growth media are used? How was the organism identified as Aspergillus? Whether only Aspergillus can be isolated from the. sample? Or any other bacterial or fungal agents? Also, based on macro and microscopic morphology, the species of Aspergillus can also be identified. Line 140-145: If the etiological agent was purely Aspergillus, how did the otitis recur on +70 days? So, it indicates a mixed infection? Line 169-172: What will be the color of the discharge if Mucorales were the etiological agent? Whether all the species of Aspergillus, including A. flavus, A. niger, A. fumigatus, etc, produce black discharge? Line 172-173: What was the color of the discharge in the present study? Line 178-181: However, in the present study, after the diagnosis of Aspergillus infection was made, clotrimazole and fluconazole drops were prescribed along with the continued use of ciprofloxacin 0.3% dexamethasone 0.1% combination ear drops and oral moxifloxacin. Please clarify In the present case, what is the course of the incidents? Whether tympanic membrane perforation occurred due to Aspergillus infection or Aspergillus infection occurred after tympanic membrane perforation? Please provide the images of the Aspergillus colony and the microscopic examination after staining (LPCB)

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    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

  5. Comments to Author

    Tympanic membrane perforation following Aspergillus otitis externa is not an uncommon complication of otomycosis. The case presented is not novel and does not contribute new insights to the existing literature. It would be more valuable to collect data from a larger number of patients with fungal otitis externa and analyze the risk factors for persistent tympanic membrane perforation.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    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

  6. Comments to Author

    Dear authors If you have enough sample in your laboratory, Please determine the type of Aspergillus species (Which species??). Also, the picture of Aspergillus colony into culture medium must be shown in 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?

    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