Mucormycosis refers to infection caused by diverse fungal organisms in the order Mucorales, including those in the genera Rhizopus, Rhizomucor, and Mucor. Symptoms of rhinocerebral infection most frequently result from invasive necrotic lesions in the nose and palate, causing pain, fever, orbital cellulitis, proptosis, and purulent nasal discharge. Central nervous system symptoms may follow. Pulmonary symptoms are severe and include productive cough, high fever, and dyspnea. Disseminated infection may occur in patients who are severely immunocompromised. Diagnosis is primarily clinical, requires a high index of suspicion, and is confirmed by histopathology and culture. Treatment is with IV amphotericin B and surgery to remove necrotic tissue. Even with aggressive treatment, mortality rates are high.
(See also Overview of Fungal Infections.)
Many different species of fungi can cause mucormycosis. Each species causes similar symptoms.
Mucormycosis is most common among people with immunocompromise, people with poorly controlled diabetes (particularly those with ketoacidosis), and people receiving the iron-chelating medication deferoxamine.
The most common form of mucormycosis is
Rhinocerebral
However, primary cutaneous, pulmonary, or gastrointestinal lesions sometimes develop, and hematogenous dissemination to other sites can occur.
Cutaneous Rhizopus infections have developed under occlusive dressings but more often result from trauma when the injured areas are contaminated with soil containing fungal spores, as may occur in natural disasters or in combat-related blast injuries. Although cutaneous mucormycosis is often opportunistic, cutaneous infections may develop in immunocompetent hosts if trauma results in contamination with fungal spores.
Symptoms and Signs of Mucormycosis
Rhinocerebral mucormycosis is usually severe and frequently fatal unless diagnosed early and treated aggressively.
Necrotic lesions appear on the nasal mucosa or sometimes the palate. Vascular invasion by hyphae leads to thrombosis and to progressive tissue necrosis that may involve the nasal septum, palate, and bones surrounding the orbit or sinuses. Manifestations may include pain, fever, orbital cellulitis, proptosis, ophthalmoplegia, loss of vision, purulent nasal discharge, and mucosal necrosis.
Progressive extension of necrosis to the brain can cause signs of cavernous sinus thrombosis, seizures, aphasia, or hemiplegia.
Pulmonary mucormycosis resembles invasive aspergillosis. Pulmonary symptoms (eg, productive cough, high fever, dyspnea) are severe.
Diagnosis of Mucormycosis
Examination of tissue samples for broad, ribbon-like, nonseptate hyphae
Culture
Diagnosis of mucormycosis requires a high index of suspicion and examination of tissue samples for large nonseptate hyphae with irregular diameters and right-angle branching patterns; the examination must be thorough because much of the necrotic debris contains no organisms.
For unclear reasons, cultures may be negative, even when hyphae are clearly visible in tissues.
Microbial cell-free DNA next-generation sequencing of blood samples may be useful in diagnosis.
CT scans and x-rays often underestimate or miss significant bone destruction.
Treatment of Mucormycosis
Control of underlying condition
Lipid amphotericin B formulations
Isavuconazonium
Surgical debridement
(See also Antifungal Medications.)
Effective therapy requires that diabetes be controlled or, if at all possible, immunosuppression be reversed or deferoxamine be stopped.
A high-dose lipid amphotericin B formulation (7.5 to 10 mg/kg IV once a day) is recommended as initial therapy. Isavuconazonium is approved for primary therapy. However, clinical experience with isavuconazonium is relatively limited, and, in severely ill patients, amphotericin B likely remains the medication of choice. Posaconazole may also be effective, especially as consolidation therapy. Posaconazole has not been studied as primary therapy.
Complete surgical debridement of necrotic tissue is critical.
