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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Candida: thrush/esophagitis, candidemia, endocarditis; candidemia is treated with an echinocandin initially plus source control
- Aspergillus: invasive disease in neutropenia/transplant; CT halo sign; treat with voriconazole or isavuconazole
- Histoplasma: Ohio/Mississippi River valleys, bird/bat droppings, granulomatous pneumonia, intracellular yeasts in macrophages
- Coccidioides: Southwest desert, spherules, erythema nodosum; meningitis requires lifelong fluconazole
- Blastomyces: Great Lakes/Ohio/Mississippi, broad-based budding yeast, pneumonia plus verrucous skin lesions
- Cryptococcus: encapsulated yeast causing meningitis in AIDS/transplant; amphotericin B + flucytosine induction
Overview
Fungal infections range from superficial mucocutaneous disease to life-threatening invasive mycoses. Host immune status is the key determinant: neutropenia predisposes to Aspergillus and Candida invasion; impaired T-cell immunity predisposes to Cryptococcus, Histoplasma, and other endemic fungi; central lines and broad antibiotics predispose to candidemia. Endemic mycoses are strongly geographic and are commonly tested through travel or residence clues.
Epidemiology
Candida is a leading cause of healthcare-associated bloodstream infection. Aspergillus is ubiquitous in soil and decaying vegetation and causes invasive disease in neutropenia, hematopoietic stem cell transplant, lung transplant, high-dose steroids, and chronic granulomatous disease. Histoplasmosis is associated with Ohio/Mississippi River valleys and bat/bird droppings. Coccidioidomycosis is associated with Arizona, California Central Valley, and the desert Southwest. Blastomycosis occurs around the Great Lakes, Ohio/Mississippi River basins, and waterways.
Clinical Features
Symptoms
Oropharyngeal candidiasis: white plaques that scrape off, burning mouth; esophageal disease causes odynophagia
Candidemia: persistent fever despite antibiotics, sepsis, endophthalmitis risk, central line or TPN exposure
Invasive aspergillosis: fever, pleuritic chest pain, cough, hemoptysis in neutropenia/transplant
Histoplasmosis: fever, cough, mediastinal adenopathy; disseminated disease causes weight loss, hepatosplenomegaly, pancytopenia
Coccidioidomycosis: pneumonia with fatigue, arthralgias, erythema nodosum, desert travel
Cryptococcal meningitis: headache, fever, altered mental status, elevated opening pressure; meningismus may be subtle
Signs
Thrush: removable white plaques leaving erythematous base
Endophthalmitis findings in candidemia: visual symptoms or retinal lesions
Pulmonary crackles may be minimal despite invasive mold disease
Hepatosplenomegaly, lymphadenopathy, mucosal ulcers in disseminated histoplasmosis
Verrucous or ulcerative skin lesions in blastomycosis
Papilledema or cranial nerve palsies from cryptococcal intracranial hypertension
Investigations
First-line
Culture and histopathologyTissue diagnosis often required for invasive fungal disease; morphology can be high-yield
Blood culturesCandida often grows in blood cultures; molds usually do not
Chest CTNodules, cavitation, halo sign in invasive aspergillosis; mediastinal adenopathy in histoplasmosis; pneumonia patterns in endemic fungi
Second-line
Serum beta-D-glucanSupports invasive candidiasis, aspergillosis, and PCP but not cryptococcus or mucormycosis reliably
GalactomannanSerum or BAL marker for invasive aspergillosis; false positives can occur
Fungal antigen testsHistoplasma urine/serum antigen for disseminated disease; cryptococcal antigen for meningitis/disseminated cryptococcus
Specialist
Lumbar punctureCryptococcal meningitis or suspected fungal meningitis; measure opening pressure
Bronchoscopy with BALImmunocompromised pulmonary infiltrates; send fungal culture, cytology, galactomannan, PCR where available
1
Candida
- Oropharyngeal candidiasis: fluconazole if moderate/severe; topical therapy may be used for mild disease
- Esophageal candidiasis: systemic fluconazole; endoscopy if refractory or alternative diagnosis suspected
- Candidemia: echinocandin initially, remove infected central line when feasible, repeat blood cultures until cleared
- Dilated eye exam and evaluation for metastatic infection in candidemia; treat at least 14 days after clearance and symptom resolution for uncomplicated disease
2
Aspergillus and molds
- Invasive aspergillosis: voriconazole or isavuconazole first-line; reduce immunosuppression when possible
- Surgical resection may be needed for massive hemoptysis, localized refractory disease, or infected prosthetic material
- Mucormycosis clue: diabetic ketoacidosis with black nasal eschar; treat with amphotericin B and urgent debridement, not voriconazole
3
Endemic fungi
- Mild pulmonary histoplasmosis or coccidioidomycosis may be observed in immunocompetent patients if improving
- Moderate/severe or disseminated histoplasmosis/blastomycosis: liposomal amphotericin B then itraconazole
- Coccidioidal meningitis: high-dose fluconazole, often lifelong
4
Cryptococcus
- Cryptococcal meningitis: liposomal amphotericin B plus flucytosine induction, then fluconazole consolidation/maintenance
- Manage elevated intracranial pressure with repeated therapeutic lumbar punctures
- In HIV-associated cryptococcal meningitis, delay ART to reduce CNS IRIS risk
Complications
- Disseminated candidiasis: Endophthalmitis, endocarditis, hepatosplenic candidiasis
- Angioinvasion: Aspergillus can cause hemoptysis, infarction, and CNS dissemination
- Chronic pulmonary cavities: Endemic fungi can mimic TB or malignancy
- Fungal meningitis: Cryptococcus and Coccidioides can cause chronic meningitis
- IRIS: Cryptococcus and histoplasmosis can worsen after ART initiation
USMLE Step 2 CK Exam Tips
- 1Candida in blood is never a contaminant; treat and look for source/metastatic infection
- 2Neutropenic patient + pleuritic pain/hemoptysis + halo sign = invasive aspergillosis; treat with voriconazole/isavuconazole
- 3Bird/bat droppings + Ohio/Mississippi + macrophages packed with yeast = histoplasmosis
- 4Southwest desert + erythema nodosum + spherules = coccidioidomycosis
- 5Broad-based budding yeast = blastomycosis
- 6Cryptococcal meningitis = encapsulated yeast, high opening pressure, amphotericin + flucytosine
- 7Black eschar in DKA = mucormycosis; urgent amphotericin and debridement
practicetest your knowledge on fungal infections (candidiasis, aspergillosis, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis)Apply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — infectious diseases and beyond.
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