Case Presentation: 26 year old male with a history of intellectual disability, poorly controlled T1DM with Hgb A1c of 16.3% presented with right facial and orbital swelling with complete vision loss, after a recent broken tooth failing outpatient amoxicillin. He was diagnosed with right orbital cellulitis and invasive fungal sinusitis on imaging. Initial MRI brain was concerning for multifocal right sided cerebral infarcts thought to be from local spread of fungal infection. Bedside nasal endoscopies showed inflamed sinus mucosa. He was treated for MSSA positive sinus cultures, diabetic ketoacidosis and bacterial pneumonia during his stay. Antifungal therapy with amphotericin B lipid complex (ABLC) and micafungin was started on clinical suspicion, risk factors, and radiological findings, although nephrotoxicity limited dosing. Ultimately pathology confirmed diagnosis of invasive mucormycosis based on hyphae and cultures grew Rhizopus after 20 days. Initial orbital and sinus infection ultimately spread to the brain leading to cerebritis, ischemia, and multifocal right sided cerebral abscesses formation. Isavuconazole was added to ABLC. Orbital and nasal cavities were irrigated with amphotericin. Multiple orbital and cranial abscess debridements with right orbital exenteration were performed throughout his two month stay for source control. He was transitioned to liposomal amphotericin B (LAMB) with rifampin as salvage therapy. However source control was unable to be obtained after a 3 month stay and disease progression led to the decision to pursue hospice care. He was discharged on isavuconazole.
Discussion: Mucormycosis is often a fatal infection that affects immunocompromised and diabetic patients. Extensive use of steroids in the setting of COVID pandemic can predispose to this infection. Diagnosis of mucormycosis often requires biopsy for histological analysis (hyphae are broad [5 to 15 micron diameter], irregularly branched, and have rare septations) as cultures may not grow the fungus. 1,3-Beta-D-glucan and galactomannan assays will be negative. Although radiography is often non-diagnostic, fungal invasion on imaging was critical in early detection of disease and the decision to initiate treatment with ABLC in this patient. Extensive debridement of necrotic infected tissue is the main stay of therapy in addition to antifungal therapy. Extensive surgery is limited in cerebral disease. Amphotericin B is the initial drug of choice and is given usually for weeks until clinical improvement. Isavuconazole or posaconazole are used either as step down when there is improvement in disease or as salvage therapy when they cannot tolerate amphotericin B or develop renal failure respectively. Treatment is continued until clinical and radiological resolution of active disease which usually takes months but may be needed lifelong. Benefit of combination therapy (amphotericin B and echinocandin) was most pronounced with cerebral involvement in non-neutropenic patients, in small studies which showed survival benefit.However, even with early detection and maximal medical and surgical therapy, prognosis often remains poor as demonstrated in this case.
Conclusions: The diagnosis and treatment course of ROCM is challenging, however early index of suspicion is required as morbidity and mortality is high even with optimal treatment. This emphasizes the importance of strict blood sugar control. Prognosis is better if confined to sinuses and worse if infection spreads to the brain.
