Fungal Infections

Allison Taffet

Michael Kaminski

Beta-d-glucan: non-specific; elevated in candidiasis, PJP, aspergillosis, +/- histo. Negative in mucormycosis, cryptococcosis, and blastomycosis.

Candidiasis

Etiology & Pathogenesis 

  • Key species: C. albicans (most common), C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. auris. 
  • Risk factors: CVCs, broad-spectrum abx, immunosuppressed, neutropenia, abdominal surgery, TPN, dialysis, ICU stay, burn 
  • Mucosal disruption → hematogenous dissemination → metastatic seeding

Clinical Presentation by Syndrome

Diagnostics & Workup

  • Blood cultures (grow on bacterial and fungal, serial cultures every 1–2 days until clearance), TTE, consider dilated fundoscopic exam (required if vision changes)

Treatment by Syndrome 

  • Candidemia (non-neutropenic, uncomplicated): ID consult, Micafungin → step-down to fluconazole after BCx clearance if stable/susceptible; 2 weeks post-clearance; remove CVC - Neutropenic candidemia: Micafungin preferred; 2W post-clearance + neutrophil recovery 
  • Endocarditis: High-dose mica OR Ampho ± flucytosine → consider fluconazole suppression; valve surgery, ID consult
  • CNS: Ampho ± flucytosine → fluconazole step-down; remove devices if present, ID consult 
  • Endophthalmitis: Fluconazole or voriconazole (systemic), +/- intravitreal injection 
  • Candida UTI: Fluconazole 200 mg x14D (if susceptible) 
  • OPC/esophageal: Fluconazole first-line; micafungin or voriconazole if refractory; x14d 
  • Vulvovaginal: Single-dose fluconazole 150 mg (uncomplicated); weekly fluconazole x6M (recurrent)

Aspergillosis

Syndrome

Key Features
Candidemia Fever, sepsis; CVC often source
Hepatosplenic RUQ pain, ↑LFTs post-neutropenia recovery
Endocarditis Persistent fungemia, emboli, new murmur
CNS Meningitis, brain abscess (post-neurosurgery or dissemination)
Endophthalmitis Visual changes; occurs in up to 16% of candidemic patients
UTI Candiduria; usually colonization unless symptomatic/high-risk
Oropharyngeal, Esophageal White plaques, dysphagia/odynophagia; HIV, steroids, malignancy
Vulvovaginal Pruritus, thick discharge; complicated if recurrent or non-albicans

Etiology & Pathogenesis 

  • Ubiquitous mold; primary portal: inhalation of conidia 
  • Key host defects: prolonged neutropenia, allogeneic HSCT, SOT, steroids, CGD, advanced AIDS 
  • Pathogenesis: angioinvasion → tissue necrosis (IPA); airway colonization → allergic syndromes

Clinical Syndromes 

  • Invasive Pulmonary (IPA): fever, cough, pleuritis in immunocompromised; halo sign on CT
  • Tracheobronchitis: ulcerative vs. pseudomembranous; predominantly lung transplant recipients 
  • Disseminated: CNS (abscesses, stroke), endocarditis, osteomyelitis, cutaneous lesions 
  • Chronic Cavitary (CCPA): >3M Sxs, cavitation, minimal immunocompromise 
  • Aspergilloma: fungal ball in pre-existing cavity; hemoptysis 
  • ABPA: poorly controlled asthma/CF, elevated IgE, bronchiectasis, mucoid impaction 
  • Allergic Fungal Rhinosinusitis: nasal polyposis, eosinophilic mucin, hyphae on pathology

Diagnostics

  • Imaging: chest CT (halo sign, air crescent, nodules); MRI for CNS/sinus 
  • Biomarkers: serum/BAL GM (best in heme malignancy/HSCT); BDG (sensitive, non-specific) 
  • Bronchoscopy/BAL: culture, cytology, GM, BDG

Treatment by Syndrome

Minimum 6–12W. Secondary ppx may be required prior to reimmunosuppression.

Blastomycosis

  • Endemic in Great Lakes, Ohio/Mississippi River valleys 
  • Mostly pulmonary manifestations, 25-40% of infections have extrapulmonary involvement (skin, bone, GU, and CNS presentations) careful Hx and PE to determine if need specific imaging 
  • Pulmonary symptoms common: dyspnea, cough, fever, hemoptysis, chest pain. Verrucous skin lesions with irregular borders. Osteolytic bone lesions. Draining sinuses 
  • Serum and urine blasto Ag, Ab testing less useful in acute disease (interpret with caution) 
  • Pulmonary blastomycosis Treatment 
    • Mild to Moderate: itraconazole 6-12M 
    • Moderate to Severe: ampho followed by itraconazole for 6-12M 
    • Immunosuppressed pt, especially pts with AIDS: start with ampho regardless of severity 
  • Disseminated extrapulmonary blasto: ampho followed by itraconazole for ~12M 
  • CNS blasto: 4-6W of ampho >> ~12M of itraconazole

Histoplasmosis

Syndrome

Primary

Alternative
IPA Voriconazole Posaconazole; Ampho
CNS Voriconazole Posaconazole; Ampho
Endocarditis Voriconazole + surgery Ampho
CCPA Itraconazole or voriconazole ≥6M Posaconazole
Aspergilloma Surgical resection if symptomatic Observation if asymptomatic
ABPA Itraconazole + corticosteroids Voriconazole/posaconazole
Prophylaxis (high-risk) Posaconazole Voriconazole

Etiology & Pathogenesis 

  • Histoplasma capsulatum (thermally dimorphic fungus) transmitted inhalation of conidia from soil (bird/bat droppings), yeast form disseminates via macrophages 
  • Endemic to Ohio/Mississippi River valleys (midwestern US) 
  • Severity determined by inoculum size and host cell-mediated immunity. Risk factors for dissemination: HIV, transplant, TNFa inhibitors, elderly 
  • DDx: TB, malignancy, sarcoidosis, other fungal infection

Clinical Presentation by Syndrome

Diagnostics & Workup 

  • Antigen (urine and serum), +/- Abs 
  • If noninvasive w/u negative: BAL with cytology, histo Ag, BDG, fungal Cx. If biopsy, need GMS/PAS stains 
  • If neuro Sxs: CT head, LP with histo Ag, routine meningitis studies

Treatment by Syndrome 

  • Therapeutic drug monitoring for itra (goal between 1 and ~4), also done for posa and vori. Target level depends on syndrome being treated 
  • Disseminated disease: histo urine Ag trended to undetectable. If uptrends, c/f treatment failure

Syndrome

Features
Asymptomatic Incidental nodule on imaging; urine/serum Ag or Ab evidence of infection
Mild Acute Pulmonary Cough, fever, dyspnea, chest discomfort, not activity limiting
Moderate Acute Pulmonary Symptoms limiting activities, +/- new O2 requirement
Severe Acute Pulmonary Respiratory failure, weight loss, ICU-level care
Disseminated Immunocompromised host; hepatosplenomegaly, cytopenias, mucosal lesions, meningitis/AMS
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