The dramatic invasive infections caused by the Zygomycetes are well known to clinicians. Within the class Zygomycetes, the order Mucorales contains the genera Rhizopus, Mucor, and Rhizomucor, which cause most cases of human infection. These fungi are found in soil, in decaying vegetation, in manure, and on a variety of foodstuffs, including bread, fruits, and seeds. Aerosolization of the spores occurs easily and leads to tissue invasion via the respiratory tract (in most patients). Occasionally, acquisition is through disrupted cutaneous barriers, as occurs with trauma and burn victims, or is from ingestion of contaminated foodstuffs, leading to gastrointestinal infection. Risk factors for development of infection with the Zygomycetes include poorly controlled diabetes mellitus, hematologic malignancies (especially with neutropenia), receipt of a solid-organ or hematopoietic stem cell transplant (HSCT), deferoxamine therapy for iron or aluminum overload states, burn wounds, and corticosteroid therapy [1]. The most dramatic presentations are in patients with diabetes who have ketoacidosis and who tend to have rhinocerebral (rather than pulmonary) zygomycosis. In this issue of Clinical Infectious Diseases, Siwek et al.[2] document an increased rate of zygomycosis in patients receiving HSCTs at the University of Iowa. The cases of 4 patients, all of whom died, are reported. These patients had all received voriconazole for prophylaxis prior to or at the time of the transplantation, and all were markedly immunosuppressed. All 4 had received allogeneic transplants, had aggressive therapy for biopsyproven or presumed graft-versus-host disease (GVHD), and 3 of the 4 had received antithymocyte globulin. The date of onset of the fungal infection is impossible to determine, but it appears that 3 of the 4 patients were never discharged from the hospital and died at or before day 70 after transplantation. As is so frequently the case, the diagnosis was made only at necropsy. Siwek et al.[2] note that there were no cases of zygomycosis among HSCT recipients in the preceding 3 years, and then, in less than 1 year, they saw these 4 cases, out of a total of 45 transplants performed (a rate of 8.9%). These data are remarkably similar to data in a recent report from Boston [3] and are also similar, in some respects, to data in a soon-to-be-published report from Seattle [4]. In the Boston experience, during a 10-month period, 4 (3.2%) of 124 HSCT recipients developed zygomycosis [3]. The prior rate at their institution during the preceding 32-month period was 2 cases among 370 patients (a rate of 0.5%). All patients who developed zygomycosis had received an allogeneic transplant, and all had GVHD. In 3 of the 4 patients, voriconazole was used for prophylaxis, and, in the fourth, it was used as empirical therapy. These patients developed zygomycosis between day 67 and day 925 after transplantation. The report from Seattle [4] differs from the others in that the 6 patients who had zygomycosis were from a cohort of 139 patients who, from 1998 through 2003, had received voriconazole either for treatment of invasive aspergillosis or fusariosis (4 patients) or for prophylaxis (2 patients)[4]. Only 3 of the 6 patients had GVHD, and only 2 appeared to be receiving corticosteroids.

Do these reports reflect a true increase in the incidence of infection with Zygomycetes? Previous reports of fungal infections in recipients of bone marrow transplants or HSCTs show zygomycosis to be an uncommon infection, accounting for only 1%–2% of all cases of invasive non-Candida fungal infection [5–7]. Review of data from several large transplant centers shows an apparent increase in the incidence of …