Agents of Mucormycosis

Mucormycosis (formerly zygomycosis) is an uncommon but emerging infection that occurs in immunocompromised patients, including children and neonates. Previously, the term zygomycosis was used to refer to syndromes of mucormycosis and entomophthoromycosis, but updates in taxonomy determined that the phylum name Zygomycota is invalid. Because the phylum Zygomycota no longer exists, the term zygomycosis has become obsolete. ^, Molds causing these infections are now in the phyla Mucoromycota, Basidiobolomycota, and Entomophthoromycota, subphyla Mucoromycotina, Basidiobolomycotina, and Entomophthoromycotina, respectively. ^, Infectious agents in the orders Entomophthorales and Basidiobolales (e.g., the genera Conidiobolus and Basidiobolus ) produce distinct cutaneous and subcutaneous disease syndromes that are not discussed in this chapter. Because clinically significant genera are in the subphylum Mucoromycotina, order Mucorales, the term mucormycosis is a useful clinical and valid mycologic reference. ^, Organisms in this order are characterized by the formation of broad, aseptate, or rarely septate hyphae and by sexual reproduction with formation of zygospores. The Mucorales are divided into several families of significance in human or animal disease, although most cases of human infection are caused by members of the family Mucoraceae. These families have undergone taxonomic revisions based on molecular, physiologic, and phylogenetic studies, including the reclassification of the genus Absidia (in part) to the family Lichtheimiaceae for pathogenic species that are able to survive at temperatures of ≥37°C. The family Mucoraceae produces sporangiospores (asexual spores) in a closed, sac-like structure called a sporangium that are released when the wall ruptures. The sporangium is attached to the hyphal substratum with a stalk-like structure, the sporangiophore. Different species are distinguished by the microscopic appearance of the sporangiophores, sporangia, and sporangiospores, as well as by the presence or absence of rhizoids (root-like structures) that anchor sporangiophores to the substratum. In the family Mucoraceae, members of the genera Rhizopus, Mucor, Actinomucor, Rhizomucor, and Apophysomyces all have been implicated in human disease. Less frequently reported genera in human disease in other families include Cunninghamella, Saksenaea, Syncephalastrum, Cokeromyces, and Lichtheimia . ^,

The species isolated from cases of human infection are ubiquitous in decomposing organic matter such as spoiled bread, fruit, and other food items, as well as in soil. The most commonly encountered human pathogen is Rhizopus arrhizus ( R. oryzae ) , but many other species have been implicated. ^, All these organisms cause similar syndromes in children and neonates. ^,

Mucormycosis generally is acquired through inhalation of spores; the lungs and sinuses are the most common initial sites of infection. Less commonly, disease can arise after ingestion of contaminated foods or by direct inoculation following trauma or through vascular catheters, an important route of nosocomial transmission in neonates. ^, In an immunocompetent host, pulmonary macrophages ingest and kill inhaled sporangiospores. ^, In diabetic hosts and other immunosuppressed patients, macrophages fail to suppress spore germination. Once infection is established, neutrophils have a pivotal role in killing hyphae. Severe neutropenia increases the risk of invasive infection, as does ketoacidosis in diabetic patients because of abnormal neutrophil function.