Fungal Infections

Opportunistic fungal infections

Many fungi are opportunists and are usually not pathogenic except in an immunocompromised host. Causes of immunocompromise include AIDS, azotemia, diabetes mellitus, lymphoma, leukemia, other hematologic cancers, burns, and therapy with corticosteroids, immunosuppressants, or antimetabolites. Patients who spend more than several days in an ICU can become compromised because of medical procedures, underlying disorders, and/or undernutrition.

Typical opportunistic systemic fungal infections (mycoses) include

Systemic mycoses affecting severely immunocompromised patients often manifest acutely with rapidly progressive pneumonia, fungemia, or manifestations of extrapulmonary dissemination.

Primary fungal infections

Primary fungal infections usually result from inhalation of fungal spores, which can cause a localized pneumonia as the primary manifestation of infection.

In immunocompetent patients, systemic mycoses typically have a chronic course; disseminated mycoses with pneumonia and septicemia are rare and, if lung lesions develop, usually progress slowly. Months may elapse before medical attention is sought or a diagnosis is made. Symptoms are rarely intense in such chronic mycoses, but fever, chills, night sweats, anorexia, weight loss, malaise, and depression may occur. Various organs may be infected, causing symptoms and dysfunction.

Primary fungal infections may have a characteristic geographic distribution, which is especially true for the endemic mycoses caused by certain dimorphic fungi. For example,

  • Coccidioidomycosis: Confined primarily to the southwestern US, Washington, northern Mexico, and Central and South America

  • Histoplasmosis: Occurring primarily in the eastern and Midwestern US and parts of Central and South America, Africa, Asia, and Australia

  • Blastomycosis: Confined to North America and Africa

  • Paracoccidioidomycosis (formerly, South American blastomycosis): Confined to that continent

However, travelers can manifest disease any time after returning from endemic areas.

When fungi disseminate from a primary focus in the lung, the manifestations may be characteristic, as for the following:

  • Cryptococcosis: Usually, chronic meningitis

  • Progressive disseminated histoplasmosis: Generalized involvement of the reticuloendothelial system (liver, spleen, bone marrow)

  • Blastomycosis: Single or multiple skin lesions or involvement of the prostate

  • Coccidioidomycosis: Bone and joint infections, skin lesions, and meningitis

Diagnosis

  • Cultures and stains

  • Histopathology

  • Serologic tests (mainly for Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, and Histoplasma)

If clinicians suspect an acute or a chronic primary fungal infection, they should obtain a detailed travel and residential history to determine whether patients may have been exposed to certain endemic mycoses, perhaps years previously.

Pulmonary fungal infections must be distinguished from tumors and chronic pneumonias caused by nonfungal organisms such as mycobacteria (including TB). Specimens are obtained for fungal and mycobacterial culture and histopathology. Sputum samples may be adequate, but occasionally bronchoalveolar lavage, transthoracic needle biopsy, or even surgery may be required to obtain an acceptable specimen.

Fungi that cause primary systemic infections are readily recognized by their histopathologic appearance. However, identifying the specific fungus may be difficult and usually requires fungal culture. The clinical significance of positive sputum cultures may be unclear if they show commensal organisms (eg, Candida albicans) or fungi ubiquitous in the environment (eg, Aspergillussp). Therefore, other evidence (eg, host factors such as immunosuppression, serologic evidence, tissue invasion) may be required to help establish a diagnosis.

Serologic tests may be used to check for many systemic mycoses if culture and histopathology are unavailable or unrevealing, although few provide definitive diagnoses. Particularly useful tests include the following:

  • Measurement of organism-specific antigens, most notably from Cryptococcus neoformans, Histoplasma capsulatum, and Aspergillus sp (occasional cross-reactivity with other fungi has been noted with each of these serologic tests)

  • Serum beta-glucan, which is often positive in invasive candidiasis as well as Pneumocystis jirovecii infections

  • Complement fixation assays and newer enzyme immunoassays for anticoccidioidal antibodies, which are satisfactorily specific and do not require proof of rising levels (high titers confirm the diagnosis and indicate high risk of extrapulmonary dissemination)

Most other tests for antifungal antibodies have low sensitivity, specificity, or both and, because measurement of acute and convalescent titers is required, cannot be used to guide initial therapy.

by Sanjay G. Revankar, MD