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Mucormycosis represents a group of life-threatening infections caused by fungi of the order Mucorales. Recent reclassification has abolished the class Zygomycetes and placed the order Mucorales in the subphylum Mucoromycotina. Therefore, infection caused by the Mucorales is most accurately referred to as mucormycosis, although the term zygomycosis may still be used by some sources. Mucormycosis is highly invasive and relentlessly progressive, resulting in higher rates of morbidity and mortality (>40%) than many other infections. A high index of suspicion is critical for diagnosis, and early initiation of therapy—often before confirmation of the diagnosis—is necessary to optimize outcomes.

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Etiology

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Fungi of the order Mucorales belong to six families, all of which can cause mucormycosis. Among the Mucorales, Rhizopus oryzae (in the family Mucoraceae) is by far the most common cause of infection. Less frequently isolated species of the Mucoraceae family that cause a similar spectrum of infections include Rhizopus microsporus, Rhizomucor pusillus, Mycocladus corymbifer (formerly Absidia corymbifera), Apophysomyces elegans, and Mucor species (which, despite its name, is a rare cause of mucormycosis). Increasing numbers of cases of mucormycosis due to infection with Cunninghamella species (family Cunninghamellaceae) have also been reported. Rare case reports have demonstrated the ability of fungi in the remaining families of the Mucorales to cause mucormycosis.

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Pathogenesis

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The Mucorales are ubiquitous environmental fungi to which humans are constantly exposed. These fungi cause infection primarily in patients with diabetes or defects in phagocytic function (e.g., associated with neutropenia or glucocorticoid treatment). Patients with elevated levels of free iron, which supports fungal growth in serum and tissues, are likewise at increased risk for mucormycosis. In iron-overloaded patients with end-stage renal failure, treatment with deferoxamine predisposes to the development of rapidly fatal disseminated mucormycosis; this agent, an iron chelator for the human host, serves as a fungal siderophore, directly delivering iron to the Mucorales. Furthermore, patients with diabetic ketoacidosis (DKA) are at high risk of developing rhinocerebral mucormycosis. The acidosis causes dissociation of iron from sequestering proteins in serum, resulting in enhanced fungal survival and virulence. It is likely that hyperglycemia during DKA also contributes to the risk of mucormycosis through its association with poorly characterized defects in phagocytic function.

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Epidemiology

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Mucormycosis typically occurs in patients with diabetes mellitus, solid organ or hematopoietic stem cell transplantation (HSCT), prolonged neutropenia, or malignancy. In patients undergoing HSCT, mucormycosis develops at least as commonly during nonneutropenic as during neutropenic periods, probably because of glucocorticoid treatment of graft-versus-host disease. Mucormycosis can occur as isolated cutaneous or subcutaneous infection in immunologically normal individuals after traumatic implantation of soil or vegetation, after maceration of the skin by a moist surface, or in nosocomial settings via direct access through intravenous catheters or subcutaneous injections.

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Patients receiving antifungal prophylaxis with either itraconazole or voriconazole may be at increased risk of mucormycosis. These patients typically present with disseminated ...

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