Acute invasive fungal sinusitis with orbital cellulitis from Cambodian tertiary hospital: a case report

Acute invasive fungal sinusitis with orbital cellulitis from Cambodian tertiary hospital: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Acute invasive fungal sinusitis with orbital cellulitis from Cambodian tertiary hospital: a case report Cheapov Tech This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8338664/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective We intend to study treatments outcomes of a patient undergoing functional endoscopic sinus surgery diagnosed with an invasive fungal sinusitis and showed biggest management challenges. Methods a case report of a patients who had come to emergency department in late stage with complication to orbital cellulitis resulted with an abscess of cerebral frontal due to late diagnosis and poor access to public health service at poor resources setting like Cambodia. In this study, a delay around three days for making the diagnosis and required an aggressive medical or surgical intervention to prevent life threatening result. Result the patient survived around three months post endoscopic sinus surgery and hemi-maxillectomy. The condition of patient undermined by immunocompromising factors of diabetes and cardiopathy resulted in pneumonia and pleurisy. The patient undergoing three surgeries including eye exenteration, surgical debridement of sinus, incision & draining of cerebral abscess, however, blood glucose was not stable, with hyperglycemia and amphotericin B injection led to renal failure despite urgent medical and surgical intervention with multi-disciplinary team. Future study on how to properly manage this grave disease is needed to provide a better safe and care for future patients. In sum, the invasive fungal sinusitis is a life-threatening sinus disease that left patient with lethal complication despite prompt medical or surgical intervention. Aspergillus Invasive fungal sinusitis functional endoscopic sinus surgery diabetes mellitus multi-disciplinary care Figures Figure 1 Figure 2 Figure 3 Introduction Acute invasive fungal sinusitis (AIFS) is a rare but life-threatening disease which resulted with lethal complication. This case report presents a 58-year-old man with uncontrolled diabetes diagnosed with AIFS complicated to rhino-cerebral mucormycosis. The aggressive nature of invasive fungal sinusitis in immunocompromised patients whether due to mucormycosis further perplexed treatment and often carried poor prognosis. Geographically, Cambodia located in tropical area associated with increasing of high sugar diet might be a favorable factor for fungus species evolving as an opportunistic infection notably in immunocompromised patients. The role of medical bacteriologist and public health expert hold the key in preventing the high mortality rate of this grave disease 1 , 2 , 3 . OBJECTIVES This study aims to evaluate the effectiveness of medical and surgical intervention for AIFS due to mucormycosis including endoscopic sinus debridement, hemi-maxillectomy and orbital exenteration at tertiary centre - Calmette hospital. It also highlights not only the managements challenges but also emphasized that results may not align with existing literature-based approaches. METHODS AND MATERIALS Study Design This study is a case report based on the medical records of a patient diagnosed with acute fungal sinusitis due to mucormycosis, managed at the Department of Otorhinolaryngology (ENT), Calmette Hospital. Study Period November 2024 to January 2025. Data Collection Clinical and diagnostic data were collected retrospectively from the patient’s medical records, including: ENT endoscopic findings and ophthalmology consultation reports Histopathological (pathology) reports Imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI) Treatment history and clinical progression Surgical Interventions The patient underwent the following surgical procedures: Endoscopic sinus debridement Incision and drainage of frontal abscess with orbital exenteration Hemi-maxillectomy Medical Management Antifungal therapy: Liposomal Amphotericin B injection, 50 mg every 12 hours Antibiotic therapy: Meropenem 3 g and Vancomycin 2 g Antidiabetic management: Intravenous Actrapid and oral Empagliflozin Outcome The patient survived during the study period from November 2024 until January 2025. Ethical Considerations The study was approved by the appropriate institutional ethics committee. All methods were performed in accordance with the relevant guidelines and regulations, including the World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, and the CARE Guidelines (CAse REport Guidelines). Written informed consent was obtained from the patient for publication of this case report and accompanying images. RESULTS The patient initially presented to the emergency department suspected signs of orbital cellulitis, including eyelid swelling and erythema, as well as nasal purulence and fever. With these symptoms, an acute invasive fungal sinusitis should be highly suspected 4 , 5 . However, a delay of approximately three days occurred simultaneously with endoscopic finding of black eschar in the inferior and middle turbinate obstructed nasolacrimal duct at right nasal cavity 6 , 7 , 8 . Around three days after pathological report, Amphoterin B injection 50mg every 12 hours initiated. He underwent multiple surgical intervention including endoscopic sinus debridement. Specifically, one month after sinus surgery, patient had cerebral frontal abscess, an incision and drainage were done followed by orbital exenteration and hemi-maxillectomy. Despite these efforts, he survived only three months post operatively based on discussion of multi-disciplinary team. Actually, current literature reviews about this grave disease showed high mortality rate. However, by reversing the immunocompromising factors including uncontrolled diabetes, infectious factors and other underlying disease might hold a key to treat this grave disease. On the other hand, prolonged hospitalization periods resulted with hospital acquired disease and emergence of multi drug resistance created significant challenges for the multidisciplinary team in optimizing treatment and patient care. This case underscores the aggressive and refractory nature of AIFS particularly in immunocompromised patients. Hopefully, further researched about new treatment like biological therapies in AIFS can improve patient’s survival rate and outcomes in such high-risk cases 9 , 10 . Discussion Acute invasive fungal sinusitis is a rare but life-threatening condition that frequently results in severe and often fatal complications, particularly in high risk patient 5 . The report of a 58-year-old man analyze with uncontrolled diabetes mellitus was diagnosed with AIFS complicated to rhino-cerebral mucormycosis. Patients with uncontrolled diabetes are especially susceptible to mucormycosis due to impaired neutrophil function, hyperglycemia, and an acidic environment that favors fungal growth. However, histopathological examination is considered to be the most reliable means of diagnosis. 29 The presence of hyphae with specific characteristic features such as regular septa, uniform shape, and 3–6 µm hyphae are typical. The aggressive angioinvasive nature of mucormycosis leads to rapid tissue necrosis, vascular thrombosis, and potential intracranial extension, which significantly complicates management and contributes to a poor prognosis. In such patients, disease progression is often fulminant despite early surgical intervention and systemic antifungal therapy. The present case highlights the diagnostic and therapeutic challenges associated with AIFS and underscores the high mortality risk once cerebral involvement occurs. The survival at end of hospital stay was 72.7% and at six months after end of study period was 57.8 percent 11 . Initial treatment should be at high doses for at least two weeks, although first-line therapy has been reported to fail in at least 50% of patients 9 , 11 . However, histopathological examination is considered to be the most reliable means of diagnosis. The presence of hyphae with specific characteristic features such as regular septa, uniform shape, and 3–6 µm hyphae are typical. The underlying condition and site of infection are important prognostic factors 5 . All immunosuppressive conditions including old age, solid-organ transplantations, haematological malignancies, use of immunosuppressive regimens for autoimmune diseases, HIV, and intensive chemotherapy have been reported as the most important risk factors for invasive fungal infection 6 . From a geographical and epidemiological perspective, Cambodia’s tropical climate, combined with changing lifestyle factors such as increased consumption of high-sugar diets, may contribute to a rising prevalence of opportunistic fungal infections among vulnerable populations. These environmental and metabolic factors may create favorable conditions for pathogenic fungal species to proliferate, particularly in individuals with poorly controlled diabetes. To prevent and to reduce of mortality rate associated with AIFS require a multidisciplinary approach, involving early clinical suspicion by otolaryngologists, prompt histopathological confirmation by medical bacteriologists and mycologists, in meantime with prompt aggressive medical management of underlying metabolic disorders. Furthermore, public health interventions aimed at improving diabetes control, patient education, and early referral systems are essential in mitigating the burden of this devastating disease 4 , 8 , 9 , 10 . CONCLUSION In sum, this case report not only highlights that acute invasive fungal sinusitis is a life-threatening disease but also reveals the rapid progression of infectious disease notably fungus species. Despite prompt antifungal treatment like amphoterin B liposomal and aggressive surgical intervention, managing this severe condition remain challenging 4 , 10 . Appropriate imaging studies and histopathological examination of excised tissue help in making the diagnosis of this infective disease and satisfactory treatment outcome can be achieved by effective surgical debridement and oral antifungal mediations. The aggressive nature of fungal sinusitis whether due to mucormycosis perplexes treatment 9 , 11 . Additionally, existing literature in both advance and resource limited healthcare system remains insufficient to fully address the complexities of this rare and aggressive disease notable in the tropical region like Vietnam, Thailand and Cambodia. With the evolution of fungal species and specific geographical regions, the role of medical bacteriologist cannot be neglected and public health expert hold the key in preventing the high mortality rate of this grave disease 8 , 11 , 12 , 13 . Declarations Ethics approval and consent to participate This case report was reviewed and formal verbal approved by the Ethics Committee of Calmette Hospital, Phnom Penh, Cambodia. Written, freely given informed consent to participate in the study was obtained from the patient. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Data Availability Statement All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding The authors received no financial support for the research, authorship, and/or publication of this article. Authors’ contributions All authors contributed to the conception of the work, data acquisition, analysis, and interpretation. All authors drafted and critically revised the manuscript and approved the final version. Acknowledgements The authors would like to thank the medical and nursing staff of ENT department- Calmette Hospital for their support in the management of this patient References Yang TL, Cheng RZ, Bing H, Hi HY et al. Diagnostic and therapeutic strategies of acute fungal sinusitis. Asian J Sur. [Internet] 2023 Jan [cited 2025 Mar 26]; 46(1):58–65. Available from: https://www.sciencedirect.com/science/article/pii/S1015958422005504 Hossein A, Bersabel W, Venkat R, Fungal. sinusitis. Natl lib of med. [Internet] 2023 Jul [cited 2025 Mar 26]; [about 1p.] Available from: https://www.ncbi.nlm.nih.gov/books/NBK551496/ Peter GD, Joshua W, Shashi P. Invasive and noninvasive fungal rhinosinusitis-a review and update of the evidence. medicine,. [Internet]. 2019 Jun [cited 2025 Mar 27] 55(319) [about p10]. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6681352/pdf/medicina-55-00319.pdf Melenie H, Jessica B, Brenton TB et al. A case of acute fungal sinusitis in an immunocompetent patient on glatiramer acetat therapy. P&M medicine [Internet] 2023 Dec [cited 2025 Mar 30]; [1p.] Available from: https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm .2023.00114. Maelle C, Thierry D, Caroline H, Emilie W et al. Invasive fungal sinusitis with ophthalmological complicaitons:case series and review literature. Pub Med Central [Internet] 2020 Jul [Cited 2025 Mar 30]; [2p]. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8210877/ Hicks M, Bishop J, Bicknell BT, Grayson J, Woodworth BA, Cho D-Y. A case of acute invasive fungal sinusitis in an immunocompetent patient on glatiramer acetate therapy. Precision Future Med. 2023;7(4):151–4. https://doi.org/10.23838/pfm.2023.00114 . Payne SJ, Mitzner R, Kunchala S, Roland L, McGinn JD. Acute Invasive Fungal Rhinosinusitis: A 15-Year Experience with 41 Patients. Otolaryngol Head Neck Surg., Chen X, Zheng M, Zhen K, Wu L, Yang D, Li Y, Z., Qin X. (2024, March 5). A case study of acute invasive fungal sinusitis complicating central retinal artery occlusion [Preprint]. Research Square. https://doi.org/10.21203/rs.3.rs-3977125/v1 Yağmur AR, Çufalı ÖF, Çolak M, et al. Invasive fungal rhinosinusitis, clinical manifestations, and prognostic values: as case series audit. Egypt J Otolaryngol. 2023;39:189. https://doi.org/10.1186/s43163-023-00551-8 . Raizada N, Jyotsna VP, Kandasamy D, Xess I, Thakar A, Tandon N. Invasive fungal rhinosinusitis in patients with diabetes. J Infect Developing Ctries. 2018;12(9):787–93. https://doi.org/10.3855/jidc.9699 . Quang LX, Tam TT, Dang LH, Chen YC, Hung SH, Tai TT, Le Vu Hoang N, Thanh NV. Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam. J Formos Med Assoc. 2024;123(3):357–365. doi: 10.1016/j.jfma.2023.08.030. Epub 2023 Sep 14. PMID: 37714767. Tran GH, Luong KA, Ngo TP, Bui TM, Luong BA, Vu HA. Invasive Fungal Rhinosinusitis: The First Histopathological Study in Vietnam. Head Neck Pathol. 2024;18(1):104. https://doi.org/10.1007/s12105-024-01711-9 . Kurokawa M, Kurokawa R, Baba A, Kim J, Tournade C, Mchugh J, Trobe JD, Srinivasan A, Bapuraj JR, Moritani T. Deadly fungi: Invasive fungal rhinosinusitis in the head and neck. Radiographics. 2022;42(7):2075–94. https://doi.org/10.1148/rg.220059 . Jacob NB, Chaney S. Rhino orbito cerebral mucormycosis: A fatal acute invasive fungal infection in uncontrolled diabetes. J Nurse Practitioners. 2016;12(9):635–9. https://doi.org/10.1016/j.nurpra.2016.06.021 . Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":436629,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eAn endoscopic image revealed on the black eschar attached to the inferior turbinate and middle turbinate obstructed the system osti-omeatal complex at the right nasal cavity associated with the blockage of nasolacrimal duct.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8338664/v1/bb95ead8c6f7b7d837cd818f.png"},{"id":98780229,"identity":"448b8663-30d3-4f1e-af8b-93abf55b2df8","added_by":"auto","created_at":"2025-12-22 12:31:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":183130,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eaxial view showed the opacity on both maxillary sinus but the nearly completed on the right side with the patient complained of the periorbital edema on arrival and obstructed the nasolacrimal duct.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8338664/v1/12259e64d7b63065be15c6cf.png"},{"id":98780509,"identity":"6afa84b5-0a53-4ac9-bd4f-d70bfc378b1f","added_by":"auto","created_at":"2025-12-22 12:31:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":252129,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ea. Axial image captured the post hemi-maxillectomy post sinus debridement one month and post incision \u0026amp;drainage of frontal abscess. An opacity of the left maxillary still existed post treatment.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eb. CT scan of head without contrast injection, sagittal plane depicted hypodense lesion, as a low-density area with a surrounding ring of enhancement on the cerebral frontal associated with surrounding edema.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8338664/v1/fa1a4f00d9b9ab3e008f0956.png"},{"id":101218480,"identity":"2823e61d-a179-42dc-a427-5b2142a6ffd5","added_by":"auto","created_at":"2026-01-27 11:13:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1470172,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8338664/v1/5fe7de7b-75d2-4f57-84db-b2e72235d1f4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute invasive fungal sinusitis with orbital cellulitis from Cambodian tertiary hospital: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute invasive fungal sinusitis (AIFS) is a rare but life-threatening disease which resulted with lethal complication. This case report presents a 58-year-old man with uncontrolled diabetes diagnosed with AIFS complicated to rhino-cerebral mucormycosis. The aggressive nature of invasive fungal sinusitis in immunocompromised patients whether due to mucormycosis further perplexed treatment and often carried poor prognosis. Geographically, Cambodia located in tropical area associated with increasing of high sugar diet might be a favorable factor for fungus species evolving as an opportunistic infection notably in immunocompromised patients. The role of medical bacteriologist and public health expert hold the key in preventing the high mortality rate of this grave disease\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"OBJECTIVES","content":"\u003cp\u003eThis study aims to evaluate the effectiveness of medical and surgical intervention for AIFS due to mucormycosis including endoscopic sinus debridement, hemi-maxillectomy and orbital exenteration at tertiary centre - Calmette hospital. It also highlights not only the managements challenges but also emphasized that results may not align with existing literature-based approaches.\u003c/p\u003e "},{"header":"METHODS AND MATERIALS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e\u003c/h2\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study is a case report based on the medical records of a patient diagnosed with acute fungal sinusitis due to mucormycosis, managed at the Department of Otorhinolaryngology (ENT), Calmette Hospital.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Period\u003c/h3\u003e\n\u003cp\u003eNovember 2024 to January 2025.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eClinical and diagnostic data were collected retrospectively from the patient\u0026rsquo;s medical records, including:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eENT endoscopic findings and ophthalmology consultation reports\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHistopathological (pathology) reports\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eImaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTreatment history and clinical progression\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003eSurgical Interventions\u003c/h3\u003e\n\u003cp\u003eThe patient underwent the following surgical procedures:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eEndoscopic sinus debridement\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eIncision and drainage of frontal abscess with orbital exenteration\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHemi-maxillectomy\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMedical Management\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAntifungal therapy: Liposomal Amphotericin B injection, 50 mg every 12 hours\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAntibiotic therapy: Meropenem 3 g and Vancomycin 2 g\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAntidiabetic management: Intravenous Actrapid and oral Empagliflozin\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcome\u003c/h3\u003e\n\u003cp\u003eThe patient survived during the study period from November 2024 until January 2025.\u003c/p\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003eThe study was approved by the appropriate institutional ethics committee. All methods were performed in accordance with the relevant guidelines and regulations, including the World Medical Association Declaration of Helsinki \u0026ndash; Ethical Principles for Medical Research Involving Human Subjects, and the CARE Guidelines (CAse REport Guidelines). Written informed consent was obtained from the patient for publication of this case report and accompanying images.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe patient initially presented to the emergency department suspected signs of orbital cellulitis, including eyelid swelling and erythema, as well as nasal purulence and fever. With these symptoms, an acute invasive fungal sinusitis should be highly suspected\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. However, a delay of approximately three days occurred simultaneously with endoscopic finding of black eschar in the inferior and middle turbinate obstructed nasolacrimal duct at right nasal cavity\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Around three days after pathological report, Amphoterin B injection 50mg every 12 hours initiated. He underwent multiple surgical intervention including endoscopic sinus debridement. Specifically, one month after sinus surgery, patient had cerebral frontal abscess, an incision and drainage were done followed by orbital exenteration and hemi-maxillectomy. Despite these efforts, he survived only three months post operatively based on discussion of multi-disciplinary team. Actually, current literature reviews about this grave disease showed high mortality rate. However, by reversing the immunocompromising factors including uncontrolled diabetes, infectious factors and other underlying disease might hold a key to treat this grave disease. On the other hand, prolonged hospitalization periods resulted with hospital acquired disease and emergence of multi drug resistance created significant challenges for the multidisciplinary team in optimizing treatment and patient care. This case underscores the aggressive and refractory nature of AIFS particularly in immunocompromised patients. Hopefully, further researched about new treatment like biological therapies in AIFS can improve patient\u0026rsquo;s survival rate and outcomes in such high-risk cases\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAcute invasive fungal sinusitis is a rare but life-threatening condition that frequently results in severe and often fatal complications, particularly in high risk patient\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The report of a 58-year-old man analyze with uncontrolled diabetes mellitus was diagnosed with AIFS complicated to rhino-cerebral mucormycosis. Patients with uncontrolled diabetes are especially susceptible to mucormycosis due to impaired neutrophil function, hyperglycemia, and an acidic environment that favors fungal growth. However, histopathological examination is considered to be the most reliable means of diagnosis.\u003csup\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e29\u003c/span\u003e\u003c/sup\u003e The presence of hyphae with specific characteristic features such as regular septa, uniform shape, and 3\u0026ndash;6 \u0026micro;m hyphae are typical.\u003c/p\u003e \u003cp\u003eThe aggressive angioinvasive nature of mucormycosis leads to rapid tissue necrosis, vascular thrombosis, and potential intracranial extension, which significantly complicates management and contributes to a poor prognosis. In such patients, disease progression is often fulminant despite early surgical intervention and systemic antifungal therapy. The present case highlights the diagnostic and therapeutic challenges associated with AIFS and underscores the high mortality risk once cerebral involvement occurs. The survival at end of hospital stay was 72.7% and at six months after end of study period was 57.8 percent \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Initial treatment should be at high doses for at least two weeks, although first-line therapy has been reported to fail in at least 50% of patients\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, histopathological examination is considered to be the most reliable means of diagnosis. The presence of hyphae with specific characteristic features such as regular septa, uniform shape, and 3\u0026ndash;6 \u0026micro;m hyphae are typical. The underlying condition and site of infection are important prognostic factors\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. All immunosuppressive conditions including old age, solid-organ transplantations, haematological malignancies, use of immunosuppressive regimens for autoimmune diseases, HIV, and intensive chemotherapy have been reported as the most important risk factors for invasive fungal infection \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFrom a geographical and epidemiological perspective, Cambodia\u0026rsquo;s tropical climate, combined with changing lifestyle factors such as increased consumption of high-sugar diets, may contribute to a rising prevalence of opportunistic fungal infections among vulnerable populations. These environmental and metabolic factors may create favorable conditions for pathogenic fungal species to proliferate, particularly in individuals with poorly controlled diabetes. To prevent and to reduce of mortality rate associated with AIFS require a multidisciplinary approach, involving early clinical suspicion by otolaryngologists, prompt histopathological confirmation by medical bacteriologists and mycologists, in meantime with prompt aggressive medical management of underlying metabolic disorders. Furthermore, public health interventions aimed at improving diabetes control, patient education, and early referral systems are essential in mitigating the burden of this devastating disease \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn sum, this case report not only highlights that acute invasive fungal sinusitis is a life-threatening disease but also reveals the rapid progression of infectious disease notably fungus species. Despite prompt antifungal treatment like amphoterin B liposomal and aggressive surgical intervention, managing this severe condition remain challenging\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Appropriate imaging studies and histopathological examination of excised tissue help in making the diagnosis of this infective disease and satisfactory treatment outcome can be achieved by effective surgical debridement and oral antifungal mediations. The aggressive nature of fungal sinusitis whether due to mucormycosis perplexes treatment\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Additionally, existing literature in both advance and resource limited healthcare system remains insufficient to fully address the complexities of this rare and aggressive disease notable in the tropical region like Vietnam, Thailand and Cambodia. With the evolution of fungal species and specific geographical regions, the role of medical bacteriologist cannot be neglected and public health expert hold the key in preventing the high mortality rate of this grave disease \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis case report was reviewed and formal verbal approved by the Ethics Committee of Calmette Hospital, Phnom Penh, Cambodia. Written, freely given informed consent to participate in the study was obtained from the patient.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003eData Availability Statement\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the conception of the work, data acquisition, analysis, and interpretation. All authors drafted and critically revised the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the medical and nursing staff of ENT department- Calmette Hospital for their support in the management of this patient\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYang TL, Cheng RZ, Bing H, Hi HY et al. Diagnostic and therapeutic strategies of acute fungal sinusitis. Asian J Sur. [Internet] 2023 Jan [cited 2025 Mar 26]; 46(1):58\u0026ndash;65. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sciencedirect.com/science/article/pii/S1015958422005504\u003c/span\u003e\u003cspan address=\"https://www.sciencedirect.com/science/article/pii/S1015958422005504\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHossein A, Bersabel W, Venkat R, Fungal. sinusitis. Natl lib of med. [Internet] 2023 Jul [cited 2025 Mar 26]; [about 1p.] Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK551496/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK551496/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeter GD, Joshua W, Shashi P. Invasive and noninvasive fungal rhinosinusitis-a review and update of the evidence. medicine,. [Internet]. 2019 Jun [cited 2025 Mar 27] 55(319) [about p10]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pmc.ncbi.nlm.nih.gov/articles/PMC6681352/pdf/medicina-55-00319.pdf\u003c/span\u003e\u003cspan address=\"https://pmc.ncbi.nlm.nih.gov/articles/PMC6681352/pdf/medicina-55-00319.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelenie H, Jessica B, Brenton TB et al. A case of acute fungal sinusitis in an immunocompetent patient on glatiramer acetat therapy. P\u0026amp;M medicine [Internet] 2023 Dec [cited 2025 Mar 30]; [1p.] Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm\u003c/span\u003e\u003cspan address=\"https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.2023.00114.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaelle C, Thierry D, Caroline H, Emilie W et al. Invasive fungal sinusitis with ophthalmological complicaitons:case series and review literature. Pub Med Central [Internet] 2020 Jul [Cited 2025 Mar 30]; [2p]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pmc.ncbi.nlm.nih.gov/articles/PMC8210877/\u003c/span\u003e\u003cspan address=\"https://pmc.ncbi.nlm.nih.gov/articles/PMC8210877/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHicks M, Bishop J, Bicknell BT, Grayson J, Woodworth BA, Cho D-Y. A case of acute invasive fungal sinusitis in an immunocompetent patient on glatiramer acetate therapy. Precision Future Med. 2023;7(4):151\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.23838/pfm.2023.00114\u003c/span\u003e\u003cspan address=\"10.23838/pfm.2023.00114\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePayne SJ, Mitzner R, Kunchala S, Roland L, McGinn JD. Acute Invasive Fungal Rhinosinusitis: A 15-Year Experience with 41 Patients. Otolaryngol Head Neck Surg., Chen X, Zheng M, Zhen K, Wu L, Yang D, Li Y, Z., Qin X. (2024, March 5). \u003cem\u003eA case study of acute invasive fungal sinusitis complicating central retinal artery occlusion\u003c/em\u003e [Preprint]. \u003cem\u003eResearch Square.\u003c/em\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21203/rs.3.rs-3977125/v1\u003c/span\u003e\u003cspan address=\"10.21203/rs.3.rs-3977125/v1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYağmur AR, \u0026Ccedil;ufalı \u0026Ouml;F, \u0026Ccedil;olak M, et al. Invasive fungal rhinosinusitis, clinical manifestations, and prognostic values: as case series audit. Egypt J Otolaryngol. 2023;39:189. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s43163-023-00551-8\u003c/span\u003e\u003cspan address=\"10.1186/s43163-023-00551-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaizada N, Jyotsna VP, Kandasamy D, Xess I, Thakar A, Tandon N. Invasive fungal rhinosinusitis in patients with diabetes. J Infect Developing Ctries. 2018;12(9):787\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3855/jidc.9699\u003c/span\u003e\u003cspan address=\"10.3855/jidc.9699\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuang LX, Tam TT, Dang LH, Chen YC, Hung SH, Tai TT, Le Vu Hoang N, Thanh NV. Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam. J Formos Med Assoc. 2024;123(3):357\u0026ndash;365. doi: 10.1016/j.jfma.2023.08.030. Epub 2023 Sep 14. PMID: 37714767.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTran GH, Luong KA, Ngo TP, Bui TM, Luong BA, Vu HA. Invasive Fungal Rhinosinusitis: The First Histopathological Study in Vietnam. Head Neck Pathol. 2024;18(1):104. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12105-024-01711-9\u003c/span\u003e\u003cspan address=\"10.1007/s12105-024-01711-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurokawa M, Kurokawa R, Baba A, Kim J, Tournade C, Mchugh J, Trobe JD, Srinivasan A, Bapuraj JR, Moritani T. Deadly fungi: Invasive fungal rhinosinusitis in the head and neck. Radiographics. 2022;42(7):2075\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1148/rg.220059\u003c/span\u003e\u003cspan address=\"10.1148/rg.220059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJacob NB, Chaney S. Rhino orbito cerebral mucormycosis: A fatal acute invasive fungal infection in uncontrolled diabetes. J Nurse Practitioners. 2016;12(9):635\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.nurpra.2016.06.021\u003c/span\u003e\u003cspan address=\"10.1016/j.nurpra.2016.06.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Aspergillus, Invasive fungal sinusitis, functional endoscopic sinus surgery, diabetes mellitus, multi-disciplinary care","lastPublishedDoi":"10.21203/rs.3.rs-8338664/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8338664/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eWe intend to study treatments outcomes of a patient undergoing functional endoscopic sinus surgery diagnosed with an invasive fungal sinusitis and showed biggest management challenges.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ea case report of a patients who had come to emergency department in late stage with complication to orbital cellulitis resulted with an abscess of cerebral frontal due to late diagnosis and poor access to public health service at poor resources setting like Cambodia. In this study, a delay around three days for making the diagnosis and required an aggressive medical or surgical intervention to prevent life threatening result.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003ethe patient survived around three months post endoscopic sinus surgery and hemi-maxillectomy. The condition of patient undermined by immunocompromising factors of diabetes and cardiopathy resulted in pneumonia and pleurisy. The patient undergoing three surgeries including eye exenteration, surgical debridement of sinus, incision \u0026amp; draining of cerebral abscess, however, blood glucose was not stable, with hyperglycemia and amphotericin B injection led to renal failure despite urgent medical and surgical intervention with multi-disciplinary team. Future study on how to properly manage this grave disease is needed to provide a better safe and care for future patients. In sum, the invasive fungal sinusitis is a life-threatening sinus disease that left patient with lethal complication despite prompt medical or surgical intervention.\u003c/p\u003e","manuscriptTitle":"Acute invasive fungal sinusitis with orbital cellulitis from Cambodian tertiary hospital: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-22 10:22:52","doi":"10.21203/rs.3.rs-8338664/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a048eee7-9579-40ae-8136-35b28782a91e","owner":[],"postedDate":"December 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-27T11:12:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-22 10:22:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8338664","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8338664","identity":"rs-8338664","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}