Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study

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In this study, we report the case of a 5-month-old immunocompetent infant who exhibited persistent dacryocystitis despite receiving broad-spectrum antibiotics. Subsequently, the patient developed ethmoiditis, orbital subperiosteal abscess, and ulceration of the hard palate. Mycological and histological samples were collected from the affected area. The combination of microscopy and PCR amplification allowed for the identification of the fungal agent Candida tropicalis. The patient underwent sinus surgery and surgical debridement, along with antifungal therapy. The treatment was successful, and the follow-up was uneventful for up to 6 months. To our knowledge, this is the first reported case of invasive sino-orbital candidiasis in an immunocompetent infant with dacryocystitis as the entry point. This study explores the clinical features, management approaches, and outcomes of this potentially fatal disease." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/13-1232/v2", "name": "Case Report: Invasive candidiasis of the head and neck in a five-month-old..." } } ] } Home Browse Case Report: Invasive candidiasis of the head and neck in a five-month-old... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Mezri S, Laabidi E, Zitouni C and Thabet W. Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.12688/f1000research.156343.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Revised Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] Sameh Mezri https://orcid.org/0000-0002-6889-4181 1,2 , Eya Laabidi 3,4 , Chaima Zitouni https://orcid.org/0009-0000-2279-3038 1,2 , Wadii Thabet https://orcid.org/0000-0002-1686-989X 3,4 Sameh Mezri https://orcid.org/0000-0002-6889-4181 1,2 , Eya Laabidi 3,4 , Chaima Zitouni https://orcid.org/0009-0000-2279-3038 1,2 , Wadii Thabet https://orcid.org/0000-0002-1686-989X 3,4 PUBLISHED 06 Jan 2025 Author details Author details 1 University of Tunis El Manar, Tunis, Tunisia 2 ENT department, Military hospital of Tunis, Montfleury, Tunis, Tunisia 3 University of Monastir, Monastir, Tunisia 4 ENT department, Taher Sfar Hospital, Mahdia, Tunisia Sameh Mezri Roles: Supervision, Writing – Review & Editing Eya Laabidi Roles: Investigation, Writing – Original Draft Preparation Chaima Zitouni Roles: Writing – Original Draft Preparation, Writing – Review & Editing Wadii Thabet Roles: Investigation OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Invasive sino-orbital fungal infection is an uncommon, yet severe condition that is rare among immunocompetent individuals, with most cases typically occurring in those with compromised immune systems. In this study, we report the case of a 5-month-old immunocompetent infant who exhibited persistent dacryocystitis despite receiving broad-spectrum antibiotics. Subsequently, the patient developed ethmoiditis, orbital subperiosteal abscess, and ulceration of the hard palate. Mycological and histological samples were collected from the affected area. The combination of microscopy and PCR amplification allowed for the identification of the fungal agent Candida tropicalis . The patient underwent sinus surgery and surgical debridement, along with antifungal therapy. The treatment was successful, and the follow-up was uneventful for up to 6 months. To our knowledge, this is the first reported case of invasive sino-orbital candidiasis in an immunocompetent infant with dacryocystitis as the entry point. This study explores the clinical features, management approaches, and outcomes of this potentially fatal disease. READ ALL READ LESS Keywords Candidiasis, invasive, pediatric, sinusitis, dacryocystitis Corresponding Author(s) Chaima Zitouni ( [email protected] ) Close Corresponding author: Chaima Zitouni Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Mezri S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Mezri S, Laabidi E, Zitouni C and Thabet W. Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.12688/f1000research.156343.2 ) First published: 15 Oct 2024, 13 :1232 ( https://doi.org/10.12688/f1000research.156343.1 ) Latest published: 06 Jan 2025, 13 :1232 ( https://doi.org/10.12688/f1000research.156343.2 ) Revised Amendments from Version 1 We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. See the authors' detailed response to the review by László Galgóczy READ REVIEWER RESPONSES Introduction Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition in which fungi invade the sinus and orbital regions. Diagnosis can be challenging and often delayed because of the nonspecific nature of the signs and symptoms. This condition has a high mortality rate, with reported mortality rates of up to 50% in severe cases, 1 primarily due to the rapid progression of the infection and complications such as septic shock or involvement of vital structures. 2 Herein, we report a case of ISOFI originating from dacryocystitis. The patient was a 5-month-old, immunocompetent infant. To the best of our knowledge, ISOFI has been reported mainly in immunocompromised patients, 2 and no study has reported it in an immunocompetent pediatric population. This case is unusual because the entry point for the infection was dacryocystitis. This study investigated the clinical features, management approaches, and outcomes of this potentially fatal disease. Case report A 5-month-old female with no previous medical history was admitted to our pediatric department with fever, medial canthal purulent discharge, tenderness, and swelling of the left eye ( Figure 1 ). Blood tests showed an elevated white blood cell count and high C-reactive protein (CRP) levels. Initial CT revealed the presence of dacryocystitis. The patient was treated with amoxicillin–clavulanate. Figure 1. Medial canthal purulent discharge of the left eye. The condition progressed with ongoing fever and, after five days, the emergence of a necrotic ulceration on the palate ( Figure 2 ). A repeat CT scan revealed ethmoiditis and an orbital subperiosteal abscess measuring 16 × 7 mm, with no evidence of bone lysis ( Figure 3 ). Figure 2. Palate ulceration. (A) At the time of diagosis. (B) After 3 weeks. (C) After 6 weeks. Figure 3. Ethmoiditis and subperiosteal abcess on CT scan. (A) Axial CT scan image demonstrating left ethmoidal sinus opacification. (B) Axial CT scan image showing subperiostal abscess in the medial wall of the left orbit. A swab of the nasal cavity, palate, and eye discharge was obtained, followed by bacteriological and mycological examinations. Biopsies of the nasal and palatine mucosae were also performed. A biopsy of the palate identified yeast with angioinvasion. Mycological examination of the biopsy samples and eye discharge revealed Candida tropicalis , which was found to be sensitive to amphotericin B, voriconazole, caspofungin, and fluconazole. The identification of the infectious agent was performed using a combination of microscopic examination and PCR amplification, which allowed for precise identification at the species level. The species-level identification was confirmed through molecular markers. To assess the antifungal susceptibility, the Clinical and Laboratory Standards Institute (CLSI) method was used. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime. In response to these findings, fluconazole was promptly initiated at a dose of 3 mg/kg per day and amoxicillin-clavulanate was replaced with high-dose ceftazidime. The patient underwent urgent surgery, which included drainage of the subperiosteal abscess through external orbitotomy, left ethmoidectomy, and surgical debridement of the ulceronecrotic palatine lesion. Immunological tests, including complete blood count, HIV serology, nitroblue tetrazolium test, HLA-DR typing, quantitative immunoglobulins (IgG, IgA, IgM), total complement activity, and lymphocyte phenotyping (CD3, CD4, CD45, CD8, B cells, and natural killer cells CD16/CD56) were normal, indicating no underlying immunosuppression. The patient responded well to the treatment. Fever and inflammatory marker levels resolved within 5 days. The canthal discharge was cleared, and the palatine tissue defect healed after six weeks. A follow-up CT scan three weeks after completing the treatment showed complete resolution of the infection. Six months after treatment, the patient remained symptom-free. Discussion Only 1.2% of all dacryocystitis cases are caused by fungal agents. 3 Aspergillus niger and Trichosporon spp , and other fungi have been reported. 4 , 5 However, Candida spp rarely affects the lacrimal drainage system. 4 Most cases occur in immunocompromised patients. 6 Cases have also been reported in patients with nasolacrimal stents, 3 dacryoliths, and ophthalmic surgery. 4 To our knowledge, only two cases of fungal dacryocystitis in the pediatric population have been reported in the literature, both of which are associated with infections caused by Aspergillus fumigatus and Aspergillus niger . 7 Our case appears to be the first instance of fungal dacryocystitis related to Candida infection in a child. In our case, dacryocystitis was the initial site of invasive fungal infection. Davies et al. 7 reported two cases of ISOFI occurring after dacryocystitis. In both cases, the patients were children aged 9–11 years with a history of leukemia under chemotherapy. 7 In contrast, our patient was significantly younger (5 months), and investigations did not reveal any immunodeficiencies. Although rare, ISOFI is most frequently observed in immunocompromised patients. 2 However, it is important to consider this diagnosis, especially if there is no improvement with antibiotic treatment even in immunocompetent patients. The diagnosis of ISOFI presents significant challenges because there are no specific clinical or imaging signs. Common symptoms include fever, nasal congestion, crusting, rhinorrhea, and lateral or retro-orbital pain. 8 , 9 Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are crucial for assessing the full extent of the infection and for surgical planning, with some data suggesting that MRI may be more sensitive than CT for diagnosis. CT can reveal bony erosion, sinus opacification, calcifications, mucosal thickening, and orbital cellulitis. MRI outlines the spread of infection through soft tissues, detects abscesses and necrosis, and assesses the impact on surrounding structures while also identifying complications. 8 , 10 Traditional microbiological techniques, light microscopy, and culture methods are generally effective for identifying Candida spp . In some cases, combining different techniques and additional specific tests, such as antigen detection and PCR, can be useful. Sometimes, the simultaneous presence of bacteria in clinical samples might be misleading, 9 as in our case, in which we noted the presence of Pseudomonas in the ocular samples. Therefore, biopsies should be repeated as needed to increase the chances of isolating fungi. 8 , 11 A treatment protocol for invasive candidiasis was established by the Infectious Diseases Society of America (IDSA) in 2016 12 and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in 2012, 13 involving initial echinocandin administration followed by a transition to azoles. 9 , 11 The duration of treatment varies across different studies and typically depends on the severity of the disease and presence of underlying comorbidities. In ISOFI, even with timely surgical debridement and adjunct systemic antifungal therapy, the mortality rate remains high, ranging from 50% to 80% (19). Rapid diagnosis, treatment, and better control of the predisposing factors for immunosuppression are essential to improve the mortality rate. 11 , 14 Conclusion In conclusion, invasive sino-orbital fungal infection is a rare and poorly documented condition, especially in children. There are no specific signs of this pathology, making it essential to consider a fungal origin in severe cases, particularly if there is no improvement with antibiotic treatment. This consideration should also be applied to immunocompetent patients, even though the condition can occur in those with normal immune status. In addition, this case highlights that dacryocystitis can serve as an entry point for this infection. Early and prolonged treatment, along with surgical intervention, is necessary. Currently, there are no specific treatment guidelines, especially when the fungal agent is Candida spp , as the available data primarily consists of case reports. Despite treatment, the mortality rate remains high, mainly because of underlying medical comorbidities and delayed diagnosis. Consent statement The authors declare that signed consent to publish was obtained from the legal guardian (parent) of the patient regarding the publication of data and findings related to this study. Data availability No data associated with this article. References 1. Alsulaiman HM, Elkhamary SM, Alrajeh M, et al. : Invasive sino-orbital aspergillosis with brain invasion in an immunocompetent pregnant patient. Am. J. Ophthalmol. Case Rep. 2021; 24 : 101210. PubMed Abstract | Publisher Full Text | Free Full Text 2. Adulkar NG, Radhakrishnan S, Vidhya N, et al. : Invasive sino-orbital fungal infections in immunocompetent patients: a clinico-pathological study. Eye. 2019; 33 (6): 988–994. PubMed Abstract | Publisher Full Text | Free Full Text 3. Toledano Fernández N, García Sáenz S, Arteaga Sánchez Á, et al. : Dacriocistitis micótica asociada a prótesis naso-lagrimal. Caso clínico. Arch. Soc. Esp. Oftalmol. 2002; 77 (7): 389–392. PubMed Abstract 4. Purgason PA, Hornblass A, Loeffler M: Atypical Presentation of Fungal Dacryocystitis. Ophthalmology. 1992; 99 (9): 1430–1432. PubMed Abstract | Publisher Full Text 5. Codère F, Anderson RL: Bilateral Candida albicans dacryocystitis with facial cellulitis. Can. J. Ophthalmol. J. Can. Ophtalmol. 1982; 17 (4): 176–177. 6. Obi E, Roy A, Bates V, et al. : Bilateral chronic fungal dacryocystitis caused by Candida dubliniensis in a neutropenic patient: Figure 1. J. Clin. Pathol. 2006; 59 (11): 1194–1195. PubMed Abstract | Publisher Full Text | Free Full Text 7. Davies BW, Gonzalez MO, Vaughn RC, et al. : Dacryocystitis As the Initial Presentation of Invasive Fungal Sinusitis in Immunocompromised Children. Ophthalmic Plast. Reconstr. Surg. 2016; 32 (4): e79–e81. PubMed Abstract | Publisher Full Text 8. Vinh D, Yim M, Dutta A, et al. : Pediatric invasive fungal rhinosinusitis: An investigation of 17 patients. Int. J. Pediatr. Otorhinolaryngol. 2017; 99 : 111–116. PubMed Abstract | Publisher Full Text 9. Pappas PG, Lionakis MS, Arendrup MC, et al. : Invasive candidiasis. Nat. Rev. Dis. Primer. 2018; 4 (1): 18026. Publisher Full Text 10. Groppo ER: Computed Tomography and Magnetic Resonance Imaging Characteristics of Acute Invasive Fungal Sinusitis. Arch. Otolaryngol. Neck Surg. 2011; 137 (10): 1005–1010. PubMed Abstract | Publisher Full Text 11. Bhandari S, Agarwal S, Bhargava S, et al. : Post Covid-19 Sinonasal Candidiasis: A Crisis Within the Pandemic. Indian J. Otolaryngol. Head Neck Surg. 2023; 75 (2): 523–528. PubMed Abstract | Publisher Full Text | Free Full Text 12. Pappas PG, Kauffman CA, Andes DR, et al. : Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016; 62 (4): e1–e50. PubMed Abstract | Publisher Full Text | Free Full Text 13. Cornely OA, Bassetti M, Calandra T, et al. : ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin. Microbiol. Infect. 2012 Dec 18; 18 : 19–37. Publisher Full Text 14. Valera FCP, Lago TD, Tamashiro E, et al. : Prognosis of acute invasive fungal rhinosinusitis related to underlying disease. Int. J. Infect. Dis. 2011; 15 (12): e841–e844. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 15 Oct 2024 ADD YOUR COMMENT Comment Author details Author details 1 University of Tunis El Manar, Tunis, Tunisia 2 ENT department, Military hospital of Tunis, Montfleury, Tunis, Tunisia 3 University of Monastir, Monastir, Tunisia 4 ENT department, Taher Sfar Hospital, Mahdia, Tunisia Sameh Mezri Roles: Supervision, Writing – Review & Editing Eya Laabidi Roles: Investigation, Writing – Original Draft Preparation Chaima Zitouni Roles: Writing – Original Draft Preparation, Writing – Review & Editing Wadii Thabet Roles: Investigation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 06 Jan 2025, 13:1232 https://doi.org/10.12688/f1000research.156343.2 version 1 Published: 15 Oct 2024, 13:1232 https://doi.org/10.12688/f1000research.156343.1 Copyright © 2025 Mezri S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Mezri S, Laabidi E, Zitouni C and Thabet W. Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.12688/f1000research.156343.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 06 Jan 2025 Revised Views 0 Cite How to cite this report: Firacative C and Gil Ó. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r365774 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-365774 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 24 Feb 2025 Carolina Firacative , Universidad del Rosario, Bogotá, Bogota, Colombia Óscar Gil , School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Bogota, Colombia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175998.r365774 The case report by Mezri et al. describes a very rare condition of a polymicrobial sino-orbital infection. However, more than a case of “Invasive candidiasis of the head and neck” this is a case of fungal and bacterial infection of ... Continue reading READ ALL The case report by Mezri et al. describes a very rare condition of a polymicrobial sino-orbital infection. However, more than a case of “Invasive candidiasis of the head and neck” this is a case of fungal and bacterial infection of the nasal cavity, palate, and eye. The title is therefore misleading as the infection was not caused by only one etiological agent and did not affect the head and neck. Polymicrobial infection should be mentioned in the introduction section rather than an invasive sino-orbital fungal infection specifically. Another important point of the case is whether the patient is considered immunocompetent or not, given that the immune system of an infant under 6 months old is not completely developed, therefore talking about the immunocompetence of this patient may carefully reviewed. In addition, discussion should be improved and conclusions should be written according with the findings of the case. Additional details need to be addressed in the description of the case. Also, it is advised that the authors consult and follow the CARE checklist of information to include when writing a case report. Major comments: How an invasive sino-orbital fungal or bacterial infection is acquired should be stated in the introduction. Is it trauma? Inhalation? Spread from the sinuses after another infection? Is it from the microbiota? Which kind of patients are mostly affected by sino-orbital infections? What is the incidence if known? Which PCR amplification was used? Which region was amplified? Reference is not stated. Detailed description should be provided. Identification at the species level is usually obtained after sequencing of a specific region. Was sequencing done? If so, the sequence should be deposited in a public database and the accession number should be provided. Which CLSI method was used to assess antifungal susceptibility? Which antifungals were tested? What were the results of this? The strain was susceptible to all antifungal tested? Authors mention that a swab of the nasal cavity, palate, and eye discharge was obtained, but they don’t mention what was done with these swabs. Did they culture them? If so, did any microorganisms grow? How was the Pseudomonas aeruginosa identified? How did you determine that P. aeruginosa was susceptible to high doses of ceftazidime? For how long was fluconazole given? Also, which was the administration route, dose and duration of the treatment with the antibiotic for P. aeruginosa ? The use of CT scan instead of MRI should be stated as a limitation, considering the comparison the authors do. Did the authors consider a possible infection of the CNS considering the proximity of the palate lesion? The discussion should be improved. There are just sentences but not related or discussed considering the case. For instance, the authors talk about the echinocandins, but they don’t mention why they didn’t use it. The authors state “Rapid diagnosis, treatment, and better control of the predisposing factors for immunosuppression are essential to improve the mortality rate.” In this case there were no predisposing factors. Also, “to decrease the mortality rate” not “to improve”. Most of the conclusions are not coming from the case report. For instance, “invasive sino-orbital fungal infection is a rare and poorly documented condition, especially in children.” (Use ISOFI as before). Or “the mortality rate remains high, mainly because of underlying medical comorbidities and delayed diagnosis”. The patient here survived. Minor comments: “…mortality rate, with reported mortality rates…” rephrase. Define CT the first time is used. Not afterwards. “ aeruginosa ” must be written in italics. Define HLA-DR. “spp” without italics and with a dot at the end (spp.). Check through the manuscript. “ A. niger ” instead of “ Aspergillus niger ” after the first time the species is mentioned. “dacryocystitis” is not a site. The lacrimal sac is. “In both cases, the patients were children aged 9 and 11 years”. “50% to 80% (19).” What is that “19”? It is redundant to state “Case report” and “A case study” in the tittle Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Microbiology, mycology, infectious diseases We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Firacative C and Gil Ó. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r365774 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-365774 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Lionakis M. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r356935 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-356935 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 24 Jan 2025 Michail Lionakis , National Institute of Allergy and Infectious Diseases, Bethesda, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175998.r356935 This is an interesting case report that describes a putatively immunocompetent infant with invasive Candida infection involving the palate, sinus, and orbit following dacryocystitis. In a child like this, it is important to discuss the possibility that ... Continue reading READ ALL This is an interesting case report that describes a putatively immunocompetent infant with invasive Candida infection involving the palate, sinus, and orbit following dacryocystitis. In a child like this, it is important to discuss the possibility that an underlying genetic etiology may account for this severe infection, particularly CARD9 deficiency that has been shown to predispose to invasive fungal infections. Thus, it is important to discuss if the patient is from a consanguineous family, which may increase the risk of an autosomal recessive disorder like CARD9 deficiency is. In addition, did the patient have oral thrush or severe diaper rash prior to this infection? Any family history of severe infections? Moreover, it would be important to discuss the possibility that CARD9 deficiency may underlie the susceptibility. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: fungal infections, fungal immunology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Lionakis M. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r356935 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-356935 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Galgóczy L. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r356531 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-356531 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 Jan 2025 László Galgóczy , University of Szeged, Szeged, Hungary Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175998.r356531 After the throughout revision of the manuscript some information must be clarified and providing some details are needed for the final acceptance. These are the followings: “The identification of the infectious agent was performed using a ... Continue reading READ ALL After the throughout revision of the manuscript some information must be clarified and providing some details are needed for the final acceptance. These are the followings: “The identification of the infectious agent was performed using a combination of microscopic examination and PCR amplification, which allowed for precise identification at the species level. The species-level identification was confirmed through molecular markers.“ – What kind of molecular markers were used for the identification at species level? Please, list them and indicate the DNA sequence similarity to a curated gene database. “To assess the antifungal susceptibility, the Clinical and Laboratory Standards Institute (CLSI) method was used.“ – Which CLSI method was applied? Please, indicate it. “ Pseudomonas aeruginosa” – Please, write “aeruginosa” in Italic “In response to these findings, fluconazole was promptly initiated at a dose of 3 mg/kg per day…” – What was the route of the fluconazole administration (oral, intraperitoneal, intravenous)? – Please, detail it. Competing Interests: No competing interests were disclosed. Reviewer Expertise: mycologist, molecular identification of human pathogenic fungi, antifungal susceptibility testing I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Galgóczy L. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r356531 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-356531 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 15 Oct 2024 Views 0 Cite How to cite this report: Galgóczy L. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.171639.r342998 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v1#referee-response-342998 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 02 Dec 2024 László Galgóczy , University of Szeged, Szeged, Hungary Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.171639.r342998 The present manuscript provide important information about a case and successful treatment of an invasive sino-orbital fungal infection caused by Candida tropicalis in immunocompetent infant. Considering that it is a unique case and the treatment was successful, the manuscript has ... Continue reading READ ALL The present manuscript provide important information about a case and successful treatment of an invasive sino-orbital fungal infection caused by Candida tropicalis in immunocompetent infant. Considering that it is a unique case and the treatment was successful, the manuscript has potential high interest among clinical mycologists. I suggest to accept the manuscript for indexing after improvement. My comments are detailed below. Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: mycologist, molecular identification of human pathogenic fungi, antifungal susceptibility testing I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Galgóczy L. Reviewer Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.171639.r342998 ) The direct URL for this report is: https://f1000research.com/articles/13-1232/v1#referee-response-342998 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 06 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, Tunisia 06 Jan 2025 Author Response Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed ... Continue reading Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Author Response: We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Author Response: We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 06 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, Tunisia 06 Jan 2025 Author Response Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed ... Continue reading Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Author Response: We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Author Response: We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 15 Oct 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 06 Jan 25 read read read Version 1 15 Oct 24 read László Galgóczy , University of Szeged, Szeged, Hungary Michail Lionakis , National Institute of Allergy and Infectious Diseases, Bethesda, USA Carolina Firacative , Universidad del Rosario, Bogotá, Colombia Óscar Gil , Universidad del Rosario, Bogotá, Colombia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Firacative C et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 24 Feb 2025 | for Version 2 Carolina Firacative , Universidad del Rosario, Bogotá, Bogota, Colombia Óscar Gil , School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Bogota, Colombia 0 Views copyright © 2025 Firacative C et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The case report by Mezri et al. describes a very rare condition of a polymicrobial sino-orbital infection. However, more than a case of “Invasive candidiasis of the head and neck” this is a case of fungal and bacterial infection of the nasal cavity, palate, and eye. The title is therefore misleading as the infection was not caused by only one etiological agent and did not affect the head and neck. Polymicrobial infection should be mentioned in the introduction section rather than an invasive sino-orbital fungal infection specifically. Another important point of the case is whether the patient is considered immunocompetent or not, given that the immune system of an infant under 6 months old is not completely developed, therefore talking about the immunocompetence of this patient may carefully reviewed. In addition, discussion should be improved and conclusions should be written according with the findings of the case. Additional details need to be addressed in the description of the case. Also, it is advised that the authors consult and follow the CARE checklist of information to include when writing a case report. Major comments: How an invasive sino-orbital fungal or bacterial infection is acquired should be stated in the introduction. Is it trauma? Inhalation? Spread from the sinuses after another infection? Is it from the microbiota? Which kind of patients are mostly affected by sino-orbital infections? What is the incidence if known? Which PCR amplification was used? Which region was amplified? Reference is not stated. Detailed description should be provided. Identification at the species level is usually obtained after sequencing of a specific region. Was sequencing done? If so, the sequence should be deposited in a public database and the accession number should be provided. Which CLSI method was used to assess antifungal susceptibility? Which antifungals were tested? What were the results of this? The strain was susceptible to all antifungal tested? Authors mention that a swab of the nasal cavity, palate, and eye discharge was obtained, but they don’t mention what was done with these swabs. Did they culture them? If so, did any microorganisms grow? How was the Pseudomonas aeruginosa identified? How did you determine that P. aeruginosa was susceptible to high doses of ceftazidime? For how long was fluconazole given? Also, which was the administration route, dose and duration of the treatment with the antibiotic for P. aeruginosa ? The use of CT scan instead of MRI should be stated as a limitation, considering the comparison the authors do. Did the authors consider a possible infection of the CNS considering the proximity of the palate lesion? The discussion should be improved. There are just sentences but not related or discussed considering the case. For instance, the authors talk about the echinocandins, but they don’t mention why they didn’t use it. The authors state “Rapid diagnosis, treatment, and better control of the predisposing factors for immunosuppression are essential to improve the mortality rate.” In this case there were no predisposing factors. Also, “to decrease the mortality rate” not “to improve”. Most of the conclusions are not coming from the case report. For instance, “invasive sino-orbital fungal infection is a rare and poorly documented condition, especially in children.” (Use ISOFI as before). Or “the mortality rate remains high, mainly because of underlying medical comorbidities and delayed diagnosis”. The patient here survived. Minor comments: “…mortality rate, with reported mortality rates…” rephrase. Define CT the first time is used. Not afterwards. “ aeruginosa ” must be written in italics. Define HLA-DR. “spp” without italics and with a dot at the end (spp.). Check through the manuscript. “ A. niger ” instead of “ Aspergillus niger ” after the first time the species is mentioned. “dacryocystitis” is not a site. The lacrimal sac is. “In both cases, the patients were children aged 9 and 11 years”. “50% to 80% (19).” What is that “19”? It is redundant to state “Case report” and “A case study” in the tittle Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Microbiology, mycology, infectious diseases We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (0) Firacative C and Gil Ó. Peer Review Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r365774) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-365774 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Lionakis M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. 24 Jan 2025 | for Version 2 Michail Lionakis , National Institute of Allergy and Infectious Diseases, Bethesda, USA 0 Views copyright © 2025 Lionakis M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This is an interesting case report that describes a putatively immunocompetent infant with invasive Candida infection involving the palate, sinus, and orbit following dacryocystitis. In a child like this, it is important to discuss the possibility that an underlying genetic etiology may account for this severe infection, particularly CARD9 deficiency that has been shown to predispose to invasive fungal infections. Thus, it is important to discuss if the patient is from a consanguineous family, which may increase the risk of an autosomal recessive disorder like CARD9 deficiency is. In addition, did the patient have oral thrush or severe diaper rash prior to this infection? Any family history of severe infections? Moreover, it would be important to discuss the possibility that CARD9 deficiency may underlie the susceptibility. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise fungal infections, fungal immunology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Lionakis M. Peer Review Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r356935) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-356935 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Galgóczy L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Jan 2025 | for Version 2 László Galgóczy , University of Szeged, Szeged, Hungary 0 Views copyright © 2025 Galgóczy L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions After the throughout revision of the manuscript some information must be clarified and providing some details are needed for the final acceptance. These are the followings: “The identification of the infectious agent was performed using a combination of microscopic examination and PCR amplification, which allowed for precise identification at the species level. The species-level identification was confirmed through molecular markers.“ – What kind of molecular markers were used for the identification at species level? Please, list them and indicate the DNA sequence similarity to a curated gene database. “To assess the antifungal susceptibility, the Clinical and Laboratory Standards Institute (CLSI) method was used.“ – Which CLSI method was applied? Please, indicate it. “ Pseudomonas aeruginosa” – Please, write “aeruginosa” in Italic “In response to these findings, fluconazole was promptly initiated at a dose of 3 mg/kg per day…” – What was the route of the fluconazole administration (oral, intraperitoneal, intravenous)? – Please, detail it. Competing Interests No competing interests were disclosed. Reviewer Expertise mycologist, molecular identification of human pathogenic fungi, antifungal susceptibility testing I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Galgóczy L. Peer Review Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.175998.r356531) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1232/v2#referee-response-356531 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Galgóczy L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 02 Dec 2024 | for Version 1 László Galgóczy , University of Szeged, Szeged, Hungary 0 Views copyright © 2024 Galgóczy L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The present manuscript provide important information about a case and successful treatment of an invasive sino-orbital fungal infection caused by Candida tropicalis in immunocompetent infant. Considering that it is a unique case and the treatment was successful, the manuscript has potential high interest among clinical mycologists. I suggest to accept the manuscript for indexing after improvement. My comments are detailed below. Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise mycologist, molecular identification of human pathogenic fungi, antifungal susceptibility testing I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 06 Jan 2025 Chaima zitouni, ENT department, Military hospital of Tunis, Montfleury, Tunisia Response to Reviewer Report by László Galgóczy, University of Szeged, Szeged, Hungary We sincerely thank Dr. László Galgóczy for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Abstract „Invasive sino-orbital fungal infection”- In fact, it is rare among immunocompetent patients. Please clarify. “Mycological and histological samples were indicative of Candida infections.- Please, discuss in details in the main text, how was the infectious agent identified. What kind of method was used? It was identified based on micromorphology or molecular markers/techniques were involved in the correct identification at species level? Introduction “Invasive sino-orbital fungal infection (ISOFI) is a severe and potentially life-threatening condition”, “the best of our knowledge, ISOFI has only been reported in immunocompromised patients” – Please provide a literature for these statements. “…and outcomes of this potentially fatal disease” – Please, discuss why it should be fatal and provide literature for this statement. Case report “Mycological examination of the biopsy samples and eye discharge revealed Candida Tropicalis, which was found to be sensitive to Amphotericin B, Voriconazole, Caspofungin, and Fluconazole. Bacterial analysis of eye discharge revealed Pseudomonas aeruginosa, which was susceptible to high doses of ceftazidime.” – As I noted for the abstract, please provide the detailed method what was used for the identification of the infectious agents. Was it only a microscopic examination or some kind of diagnostic technique was applied to identify them at species level. Were they identified based on some kind of molecular marker? Which method was used to reveal the antifungal/antibiotic susceptibility of the infectious agents? Was it a clinically approved method, such as CLSI or EUCAST? „fluconazole was promptly initiated and amoxicillin-clavulanate” – What was the applied dosage? Candida Tropicalis – Candida tropicalis (in Italic) amphotericin B, Voriconazole, Caspofungin, and Fluconazole - amphotericin B, voriconazole, caspofungin, and fluconazole Discussion Aspergillus Niger – Aspergillus niger (in Italic) Trichosporon – Trichosporon spp. (in Italic) Candida – Candida spp. (in italic) Aspergillus Fumigatus and Aspergillus Niger - Aspergillus fumigatus and Aspergillus niger (species names in Italic) Pseudomonas – Pseudomonas (in Italic) Author Response: We have made the requested modifications to the manuscript. Specifically, we clarified the rarity of ISOFI in immunocompetent patients and provided further details on the methods used to identify the infectious agents, including microscopy and molecular techniques for species-level identification. We also added the appropriate references to support the statements about the severity and potential fatality of ISOFI. In the case report, we included the details of the diagnostic techniques used for fungal and bacterial identification, as well as the susceptibility testing methods, ensuring that clinically approved methods were specified. The dosage of fluconazole has been included, and we corrected the formatting for species names as requested throughout the manuscript. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Galgóczy L. Peer Review Report For: Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study [version 2; peer review: 3 approved with reservations] . F1000Research 2025, 13 :1232 ( https://doi.org/10.5256/f1000research.171639.r342998) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1232/v1#referee-response-342998 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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