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Mucormycosis

(Zygomycosis)

By Sanjay G. Revankar, MD, Professor of Medicine and Director, Infectious Disease Fellowship Program, Division of Infectious Diseases, Wayne State University School of Medicine

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Mucormycosis refers to infection caused by diverse fungal species, including Rhizopus, Rhizomucor, and Mucor. Symptoms most frequently result from invasive necrotic lesions in the nose and palate, causing pain, fever, orbital cellulitis, proptosis, and purulent nasal discharge. CNS symptoms may follow. Pulmonary symptoms are severe and include productive cough, high fever, and dyspnea. Disseminated infection may occur in severely immunocompromised patients. 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.

Many different species of fungi can cause mucormycosis. Each species causes similar symptoms.

Mucormycosis is most common among immunocompromised people, in patients with poorly controlled diabetes (particularly those with ketoacidosis), and in patients receiving the iron-chelating drug deferoxamine.

The most common form of mucormycosis is

  • Rhinocerebral

However, primary cutaneous, pulmonary, or GI 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

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 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

  • Examination of tissue samples for broad, ribbon-like, nonseptate hyphae

  • Culture

Diagnosis of mucormycosis requires a high index of suspicion and painstaking 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.

CT and x-rays often underestimate or miss significant bone destruction.

Treatment

  • Control of underlying condition

  • Lipid amphotericin B formulations

  • Surgical debridement

(See also Antifungal Drugs.)

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/day) is recommended as initial therapy. Isavuconazole is approved for primary therapy. However, clinical experience with isavuconazole is relatively limited, and in severely ill patients, amphotericin B likely remains the drug 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.

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  • NOXAFIL
  • DESFERAL