How fungal infections are tested on Step 1
The vignette usually supplies a location or exposure, a host (healthy, diabetic, neutropenic, AIDS), and a microscopy description. The answer is the organism, the stain, or the drug mechanism.
Fungi are eukaryotes, so antibacterial ribosome and cell-wall targets do not apply. The selective targets are ergosterol in the membrane and β-glucan in the cell wall.
Endemic dimorphic fungi
These fungi infect healthy people who inhale spores in a specific region; most infections are mild but disseminate in the immunocompromised.
| Fungus | Tissue form | Classic disease |
|---|---|---|
| Histoplasma capsulatum | Small yeasts inside macrophages | Pneumonia mimicking TB; disseminated disease with hepatosplenomegaly and oral ulcers in AIDS |
| Blastomyces dermatitidis | Large yeast with broad-based budding, thick wall | Pneumonia, verrucous skin lesions, bone involvement |
| Coccidioides immitis | Spherules filled with endospores | Valley fever, erythema nodosum, desert rheumatism; meningitis |
| Paracoccidioides | Yeast with multiple buds ("captain's wheel") | Lung and mucocutaneous disease |
| Sporothrix schenckii | Cigar-shaped yeast | Rose gardener — ascending lymphocutaneous nodules; treat with itraconazole |
Spherules are larger than red cells; Histoplasma yeasts are smaller than red cells and sit inside macrophages.
Opportunistic fungi
These organisms cause severe disease when immunity is impaired — neutropenia, AIDS, diabetic ketoacidosis, or broad-spectrum antibiotic use.
Yeasts, Pneumocystis, and superficial fungi
Yeasts dominate mucosal and bloodstream infections; superficial fungi live only in keratin.
| Organism | Host and disease | Diagnosis and treatment |
|---|---|---|
| Candida albicans | Thrush (cellular immunity), vulvovaginitis (antibiotics, diabetes), esophagitis (AIDS), candidemia (catheters, neutropenia) | Germ tubes at 37 °C; pseudohyphae. Topical azole or nystatin; fluconazole; echinocandin for candidemia |
| Cryptococcus neoformans | Meningitis in AIDS (CD4 < 100); pigeon droppings | India ink, mucicarmine stain, capsular antigen. Amphotericin B + flucytosine, then fluconazole |
| Pneumocystis jirovecii | Pneumonia in AIDS (CD4 < 200) | Methenamine silver stain; ground-glass infiltrates; ↑ LDH. TMP-SMX (+ steroids if hypoxic) |
| Malassezia | Tinea versicolor — hypopigmented patches after heat and sweating | "Spaghetti and meatballs" on KOH. Selenium sulfide or topical azole |
| Dermatophytes | Tinea pedis, capitis, corporis, cruris, unguium | KOH shows branching hyphae. Topical azoles; oral terbinafine for nails |
Pneumocystis prophylaxis begins when CD4 falls below 200/mm³.
Antifungal drugs
Each class targets a step in building the membrane or wall.
| Class | Mechanism | Key toxicity |
|---|---|---|
| Amphotericin B | Binds ergosterol, forms membrane pores | Nephrotoxicity, hypokalemia, hypomagnesemia, infusion fever and rigors |
| Azoles (fluconazole, voriconazole, itraconazole) | Inhibit 14α-demethylase | P-450 inhibition; hepatotoxicity; gynecomastia (ketoconazole) |
| Echinocandins (caspofungin, micafungin) | Inhibit β-glucan synthase | Histamine release with infusion; well tolerated |
| Terbinafine | Inhibits squalene epoxidase | Hepatotoxicity, taste disturbance |
| Flucytosine | Converted to 5-FU; blocks DNA and RNA synthesis | Bone marrow suppression |
| Griseofulvin | Disrupts microtubules; deposits in keratin | Teratogenic; induces P-450 |
Nystatin is amphotericin's cousin, too toxic for systemic use and given topically or as a swish.
A 45-year-old construction worker from Phoenix develops fever, cough, painful red nodules on his shins, and arthralgias after a dust storm. Lung biopsy shows large round structures filled with small endospores. What is the organism?
- The desert Southwest and soil disruption suggest inhaled arthroconidia.
- Erythema nodosum with arthralgias is "desert rheumatism," typical of valley fever.
- Spherules filled with endospores are the tissue form of Coccidioides.
Answer. Coccidioides immitis (valley fever). Most cases resolve; disseminated or severe disease is treated with fluconazole or amphotericin B.