Although there are many reports of virtually any fungal species causing some form of healthcare-associated disease in humans, the most often encountered diseases caused by filamentous fungi are invasive aspergillosis and mucormycosis (1,4,5). There are also numerous reports of agents of hyalohyphomycosis such as Acremonium spp. and Fusarium spp. (1,6,7,8,9), but these are usually associated with an outbreak related to the use of contaminated patient-care materials or in the case of Fusarium with environmental sources and dissemination from sites of onychomycosis (10). Their frequency is much lower than Aspergillus and the Zygomycetes; thus, this chapter concentrates on the latter.

Aspergillus spp. are the most often encountered filamentous fungi in clinical practice, causing invasive, allergic, and toxic diseases. They are ubiquitous filamentous fungi found in soil, plant debris, and air. There are over 180 described species, although only 20 or so have been reported to be pathogenic for humans (1,2). Table 41-1 summarizes the Aspergillus spp. that are most commonly isolated from clinical specimens. Invasive disease can be found in almost any organ, but the most commonly affected are lungs, brain, paranasal sinuses, heart, and bones. Aspergillus fungemia is very rare, even in the setting of disseminated disease. It occurs in <10% of cases (11). Aspergillosis can also be related to medical devices such as intravenous or peritoneal catheters and prosthetic materials (12, 13 and 14,15). Invasive aspergillosis occurs almost exclusively in patients with a high degree of immunosuppression, such as that seen in leukemia and in bone marrow and solid organ transplantation. However, there are recent reports of invasive pulmonary aspergillosis in otherwise immunocompetent hosts and in patients with chronic obstructive pulmonary disease. Its incidence has been on a steady rise, as evidenced by epidemiologic and postmortem studies. Mortality is very high, reaching nearly 90% in some series of disseminated disease or in deeply immunocompromised patients, and therapy often requires intensive medical treatment with amphotericin B (or its lipid formulations), caspofungin, or voriconazole, alone or in combination, in addition to aggressive surgical debridement when appropriate (2).

Fusarium species are becoming exceedingly important in medical practice, particularly for centers that care for cancer and transplant patients. This agent is usually regarded as an agent of onychomycosis and has been implicated in an extensive outbreak of fungal keratitis related to contaminated ophthalmologic solutions; however, it can cause invasive and disseminated disease, particularly in immunocompromised patients (16). While this mold can produce invasive lung involvement, the typical presentation will be that of disseminated disease characterized by fever and disseminated skin lesions of violaceous appearance. As opposed to disseminated aspergillosis, disseminated fusariosis is one of the few mold infections that can have positive blood cultures. Healthcare-associated infection and transmission are rare, but as with other mold pathogens, environmental contamination has been implicated. Mortality is extremely high, despite antifungal therapy.

The terms mucormycosis or zygomycosis comprise a class of filamentous fungi that cause highly invasive disease in humans. The terms can be used interchangeably. The class Zygomycetes includes three orders: Mucorales, Entomophthorales, and Mortierellales. The most often encountered clinical pathogens fall in the order Mucorales, and their species are shown in Table 41-1. They are all ubiquitous fungi found in soil and decaying fruits, vegetables,
and food. These microorganisms affect immunocompromised patients, such as those with diabetic ketoacidosis, iron overload, malnourishment, leukemia, bone marrow transplant, solid organ transplant, and burns. They are also seen in patients with acquired immunodeficiency syndrome and patients receiving immunosuppressive therapies such as corticosteroids or tumor necrosis factor blockers (1,4,5). Although they can affect almost any organ or body system, the most common forms of invasive disease are rhinocerebral, pulmonary, cutaneous, and gastrointestinal. They have also been associated with medical devices such as intravascular and peritoneal catheters. Mortality is very high and prognosis is poor, even in the face of aggressive treatment.

The body of information on healthcare-associated reservoirs, transmission, and infection by filamentous fungi is constantly growing. Although the early years of studying this problem were characterized by debate, today there is little question that these microorganisms are present and can be transmitted in the hospital. Healthcare-associated acquisition of infection by filamentous fungi is extremely important for centers that have a large immunocompromised population, such as cancer or transplant centers, and great efforts and advances have been undertaken to control them.

Acquisition of these diseases is a function of a susceptible host and the presence of a pathogenic microorganism in the environment. Table 41-2 summarizes host risk factors for invasive aspergillosis and zygomycosis. As seen in the table, varying degrees of immunosuppression and underlying illness are required for the host to be susceptible.

As for the presence of the microorganisms in the hospital environment, it is now known that the main source for them is environmental contamination, which can include various surfaces, air, and water (1,4,5,12,15,17,18,19,20). Disturbances in the hospital environment, such as construction, can cause wide dissemination of the microorganisms and even outbreaks. Much of the evidence linking aspergillosis to the healthcare-associated environment comes from outbreak investigations (7,21, 22, 23, 24 and 25).