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INTRODUCTION

Mucormycosis represents a group of life-threatening infections caused by fungi of the order Mucorales of the subphylum Mucoromycotina (formerly known as the class Zygomycetes). Mucormycosis is highly invasive and relentlessly progressive, resulting in higher rates of morbidity and mortality than many other infections. Although mortality rates from mucormycosis have declined in recent years as a result of early initiation of more effective antifungal therapies, they remain high overall.

ETIOLOGY

image Fungi of the order Mucorales belong to seven families (Table 213-1), all of which can cause mucormycosis. Among the Mucorales, Rhizopus oryzae and R. delemar (a related, more recently recognized species)—both in the family Mucoraceae—are by far the most common causes of mucormycosis in the Western Hemisphere. Less frequently isolated species of the Mucoraceae that cause a similar spectrum of infections include Rhizopus microsporus, Rhizomucor pusillus, Lichtheimia corymbifera (formerly Absidia corymbifera), Apophysomyces elegans, and Mucor species. Increasing numbers of cases of mucormycosis due to infection with Cunninghamella species (family Cunninghamellaceae) have also been reported, particularly in highly immunocompromised patients. Only rare case reports have demonstrated the ability of fungi in the remaining families of the Mucorales to cause mucormycosis, although other Mucorales can be the major cause of disease in certain geographic areas (e.g., A. elegans in India and Mucor irregularis in China).

TABLE 213-1Taxonomy of Fungi Causing Mucormycosis (Subphylum Mucoromycotina, Order Mucorales)

PATHOGENESIS

The Mucorales are ubiquitous environmental fungi to which humans are constantly exposed. These fungi cause infection primarily in patients with diabetes, defects in phagocytic function (e.g., neutropenia or glucocorticoid treatment), and/or elevated levels of free iron, which supports fungal growth in serum and tissues. In the past, iron-overloaded patients with end-stage renal failure who were treated with deferoxamine had a high risk of developing rapidly fatal disseminated mucormycosis; deferoxamine is an iron chelator for the human host, but it 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, resulting in enhanced fungal survival and virulence. The ketoacid β-hydroxybutyrate increases expression of host and fungal receptors that result in fungal adherence and penetration into tissues.

Nevertheless, the majority of diabetic patients who present with mucormycosis are not acidotic, and, even absent acidosis, hyperglycemia directly contributes to the risk of mucormycosis by at least four likely mechanisms: (1) hyperglycation of iron-sequestering proteins, disrupting normal iron sequestration; (2) upregulation of a mammalian cell receptor (GRP78) ...

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