Other fungi may, under certain circumstances, produce visceral or systemic infection. The most common of these conditions are candidiasis, aspergillosis, and mucormycosis. Persons predisposed to infection include aged persons, cachectic or debilitated patients, persons with diseases such as AIDS or leukemia that affect the body’s immunologic mechanisms, and, most commonly, persons under treatment with certain drugs that impair the same immunologic mechanisms. Such drugs include many types of antileukemic or anticancer chemotherapeutic agents and sometimes adrenocortical steroids if use has been heavy or prolonged. Occasionally, overgrowth of Candida may be caused by prolonged oral antibiotic therapy that destroys normal gastrointestinal tract bacterial flora. Candida fungemia may be associated with indwelling intravenous (IV) catheters. Diagnosis in many of these patients is difficult, since the original underlying disease usually overshadows advent of the fungal infection. If the patient has a condition that predisposes to infection by fungi, culture of a fungus from an area where it is normally absent should not be disregarded as mere contamination but should be investigated further.

Candida infections

Candida organisms may be present as either normal nasopharyngeal area or gastrointestinal tract (GI) inhabitants (20%-40% of persons); as colonization without infection (10%-15% of vaginal cultures in asymptomatic women, with a range of 0%-50%); as superficial infection (e.g., the oral cavity or the vaginal area); or as deep or disseminated infection. On the other hand, in one study of Candida GI infection, only 75% had positive stool cultures. Some species are more often pathogenic than others. Of these, C. albicans is by far (up to 90%) the most frequent and important. Serious C. albicans infections (including fungemia) are associated with diabetes, extensive surgery, AIDS and other conditions (e.g., leukemia and lymphoma) producing decreased immunologic resistance, chemotherapy or immunosuppressive therapy, and also in some patients on hyperalimentation or following antibiotic therapy. Localized skin, oral mucous membrane (thrush), or vaginal infection by C. albicans (Monilia) is a fairly common fungus problem, associated with the same conditions as the more serious infections. Other Candida species of importance are C. tropicalis and C. parapsilosis. C. tropicalis infections are next in frequency to those of C. albicans, and are associated with bone marrow transplants, leukemia, and lymphomas, and with fungemia due to colonized venous catheters or with hyperalimentation (although C. albicans is still the most frequent organism). C. parapsilosis frequently colonizes the skin and grows especially well in glucose-containing solutions. It is most frequently associated with narcotic addiction and with hyperaimentation. C. krusei and C. guilliermondii are starting to appear in immunocompromised patients.

Diagnosis consists of wet-mount or stained slide preparations from accessible areas (which provide a presumptive diagnosis only), culture, and serologic tests. A potassium hydroxide (KOH) wet preparation detects Candida in about 60%-70% of vaginal KOH preparations (40%-85% of all KOH cases, depending on number of organisms present, compared to culture). One report found that nonmicrobiologists could detect only about 20%. Use of fluorescent stains such as Calcofluor white could increase detection rates. A new slide LA test for Candida antigen in vaginal specimens has recently become available through at least 3 companies, with 47%-80% sensitivity. Another LA test had 53% sensitivity. Papanicolaou-stained slides are reported to detect about 45%-50% of vaginal candidiasis.

Various serologic tests for antibody are available. The serum LA procedure is the easiest to perform. The one most often evaluated is called Cand-Tec. It has a reported sensitivity of 50%-60% (range, 30%-94%). Immunosuppressed patients tend to have lower detection rates. An IgG EIA procedure was said to have 82% sensitivity. Several tests for serum mannan, a Candida cell wall antigen, have reported sensitivity of 40%-60% (range, 29%-84%) in invasive candidiasis. At present, none of the commonly used serologic tests will reliably differentiate between superficial infection (or colonization) and deep infection, and neither will cultures from accessible specimen sites. Isolation of Candida from both blood and urine culture, however, is very suggestive of disseminated candidiasis. However, blood cultures are positive in only about 40% of cases (range, 32%-50%).

Torulopsis glabrata is a species from the genus Torula that clinically resembles Candida in many respects. It can be found normally in the human mouth, GI tract, urinary tract, and respiratory tract. As a pathogen it is most frequently found in urine. In some hospitals it may surpass C. tropicalis in frequency and is isolated under essentially the same conditions (associated with IV catheters, antibiotic therapy, Foley catheters, and extensive surgery). Pathogenicity is considered to be less than that of Candida, so that isolation may or may not be clinically significant. In one study of fungal vaginitis, C. albicans was isolated in 81% of cases and T. glabrata was second with 16%.


Aspergillus is a fungus with branching septated (bamboo-like) hyphae present normally in soil and different vegetation. In patients, A. fumigatus is most frequently isolated, followed by A. flavus and A. niger. The organism spreads through dust or airborne spores; therefore, human entry involves the respiratory tract. There is widespread exposure in the environment; but with the exception of some individuals with allergy, persons with normal immune systems usually do not develop Aspergillus-related disease. About 5%-10% of hospitalized patients have nasopharyngeal colonization. Aspergillus-related medical problems may occur in several forms.

1. Reactive allergic disease. This is caused by allergy to inhaled Aspergillus organisms without Aspergillus colonization or infection.
2. Allergic bronchopulmonary aspergillosis. This is usually associated with preexisting asthma and is a type of hypersensitivity lung disease. After inhalation, Aspergillus produces a localized small infection of the respiratory tract that is a source of antigen to an already sensitized person. Affected patients all have a history of asthma that becomes much worse. There frequently are low-grade fever and chest x-ray abnormalities of various types. However, the chest film may be normal.
3. Aspergilloma. This is a “fungus ball” type of localized infection within cystic spaces of the lung due to preexisting chronic lung disease. About 85% are located in the upper portions of the lungs. Chronic tuberculosis is the most frequent precursor (25%-72% of aspergilloma cases). An aspergilloma may be asymptomatic or may result in hemoptysis (50%-80% of cases). Cough and sputum production is also common.
4. “Invasive” aspergillosis. This may be localized, usually in the lung, or disseminated. Invasive aspergillosis is usually associated with patients with leukemia or lymphoma, patients with solid tumors undergoing chemotherapy, or patients who are immunosuppressed. The patients frequently have neutropenia. The same group of patients have a markedly increased incidence of Candida infection.

The lungs and skull sinuses are frequently involved infection sites. Contaminated air conditioning systems or air ducts have often been implicated as the source of Aspergillus infection. Diagnosis requires the same procedures that were described for candidiasis. Demonstration of Aspergillus in sputum is more alarming than finding Candida. However, colonization rather than infection may be present. In one series of patients, one third of those with Aspergillus in the sputum failed to yield evidence of Aspergillus infection. A. fumigatus and A. flavus are much more likely to be respiratory tract pathogens than the other species of Aspergillus. On the other hand, in invasive pulmonary aspergillosis, only 13%-34% produced sputum that grew Aspergillus. Biopsy of lesions with culture or tissue examination are the best ways to make a definitive diagnosis. Aspergillus typically invades blood vessel walls in tissue specimens. If biopsy material is obtained, special stains are usually needed to find and identify the organism. Various serologic test procedures have been reported, but the ones most commonly used are some type of agar gel diffusion (AGD) or ELISA. In well-established Aspergillus infections, AGD detects about 65% and the ELISA about 80%-90% (range, 57%-100%). False positive results have been reported in about 3% of the general population and in up to 25% of patients with asthma. A. fumagatus specific IgE antibody detected by ELISA or radioimmunoassay methods is reported to be present in about 85% of patients with allergic broncho-pulmonary aspergillosis but less than 20% of those with aspergilloma or Aspergillus-associated asthma. A skin test for Aspergillus that gives results similar to those of the serologic tests, including the false positive reactions, is available. A nucleic acid probe with PCR amplification has recently been reported.

In patients with aspergilloma, helpful laboratory findings include eosinophils in sputum and a peripheral blood eosinophilia. In classic cases the sputum contains golden brown plugs that contain Aspergillus hyphae. In one series, Aspergillus hyphae were seen microscopically in 40%, and sputum culture was positive in about 55%. Fiberoptic bronchoscopy is reported to increase the isolation rate (55%-100%). Results of skin tests and serologic tests are usually positive, as noted previously, but results of these tests may be positive without evidence of aspergillosis in persons with asthma.


Mucormycosis (zygomycosis) is usually caused by saprophytic bread mold fungi with nonseptate hyphae of the genus Mucor or Rhizopus. Infection is characteristically associated with diabetic ketoacidosis and is also more common in patients with leukemia or lymphoma and immunocompromised persons. Infection is most common in the nasopharynx region and paranasal sinuses. There may be spread to the brain or blood-borne dissemination. Diagnosis is through culture and biopsy.