Linking To And Excerpting From Core IM’s “Invasive Fungal Disease: 5 Pearls Segment”

Posted on June 28, 2025 by Tom Wade MD

Today, I review, link to, and excerrpt from CoreIM‘s Invasive Fungal Disease: 5 Pearls Segment.

All that follows is from the above resource.

Invasive Fungal Disease: 5 Pearls Segment
Posted: June 11, 2025
By: Dr. Samantha Schuetz, Dr. Michael Mansour, Dr. Audrey Mahajan, Dr. Andrej Spec and Dr. Shreya P. Trivedi
Graphic: Dr. Amy Mu
Peer Review: Dr. Matthew Lee, Dr. Todd McCarty, Kendell Bell PharmD

Podcast: Play in new window | Download

 Time Stamps

  • 01:46 Pearl 1: What is invasive fungal disease, and who is most at risk for developing invasive fungal disease?
  • 10:35 Pearl 2: What are the main classes of fungi?
  • 18:16 Pearl 3: Fungal Diagnostics: PCR/B-D Glucan and Galactomannan
  • 29:42 Pearl 4: Blood Cultures, Sputum/BAL cultures, Urine cultures
  • 34:14 Pearl 5: How is invasive fungal disease treated?

CME-MOC

Sponsor: Oakstone CME’s ACP MKSAP Audio Companion

Show Notes

Pearl 1: What is invasive fungal disease, and who is most at risk for developing invasive fungal disease?

  • Invasive Fungal Disease (IFD) occurs when fungi invade areas that should be sterile
    • Bloodstream infections, abscesses in visceral organs (brain, liver, kidney, and spleen)
  • The right host is important. 3 major buckets of hosts:
    • 1)Who:  Patients with suppressed immune systems, especially hematopoietic stem cell transplants, solid organ transplants on immunosuppression, patients on high dose steroids. Mechanism: Immune suppression!
    • 2) Who: Patients undergoing high risk abdominal surgery. Mechanism: direct spillage
    • 3) Who: Critically ill patients in the ICU. Mechanism: Lines are a conduit for fungal growth
    • Immunocompetent individuals can also develop IFD. Highest risk is those with structural lung disease.

Pearl 2: What are the main classes of fungi?

  • Yeasts
    • Obligate unicellular growth
    • The most clinically relevant yeasts are (most) candida and cryptococcus.
      • Invasive candidiasis is the most common IFD in non-neutropenic, critically ill adult patients in the ICU, and can have a mortality rate as high as 40% in those presenting with septic shock
      • Cryptococcus is typically inhaled and can cause lung infections, but the most feared complication is meningoencephalitis
  • Molds
    • Obligate multicellular organisms
    •  The most clinically relevant molds are Aspergillus and Mucor
      • Aspergillus spores are prevalent in the air, and those with anatomic issues in the lungs preventing secretion clearance (like bronchiectasis) or compromised immune systems are at risk.
      • Mucormycosis is particularly seen in individuals with advanced diabetes. Inhalation of Mucor spores in this setting can lead to invasive rhino-cerebral mucormycosis, that can invade sinuses, bone, and the CNS, often requiring surgical resection
      • Fusarium is a hyaline mold that causes disseminated disease in profound and prolonged neutropenia in hematologic malignancy patients. Skin manifestations resemble ecthyma gangrenosum, positive blood cultures occur in 50% of cases, and it often spreads to the lungs hematogenously with an appearance similar to septic emboli.
  • Dimorphics
    • Mold in the environment, yeast in the host. “Mold in the cold, yeast in the beast”
    • Key examples are the “endemic mycoses”: Histoplasmosis, Coccidioidomycosis, and Blastomycosis.
    • Endemic fungi are no longer strictly confined to their old historical borders
    •  Clinical Pearl: CDC now recommends testing for dimorphic fungi in patients with pneumonia who have failed one round of antibiotics.

Pearl 3: Fungal Diagnostics: PCR/B-D Glucan and Galactomannan

  • Beta D Glucan
    • “Pan-fungal marker” detects a cell wall component found in most fungi
      • Notable exceptions:  Cryptococcus, Blastomyces, and Mucorales
    • Sensitive but Non-Specific: Useful for detecting invasive candidiasis and other fungal infections, but cannot localize or specify the fungus.
    • False Positives Are Common: Can result from IVIG, certain antibiotics (e.g., Bactrim, cefepime), albumin, and dialysis (especially with older cellulose membranes).
    • High values (>500) are more suggestive of true infection; mild elevations may be false positives, especially in dialysis patients.
  • Galactomannan Antigen
    • Detects cell wall components of Aspergillus, Histoplasma, and Fusarium
    • Higher Specificity, Lower Sensitivity: Particularly for Aspergillus; may be negative even in true infections.
    • Susceptible to False Positives: Notably from antibiotics like Zosyn and Unasyn, among others.
    • Cutoffs Vary by Sample: Positive if >0.5 in serum; >1.0 in BAL fluid* is more consistent with true infection.
    • Avoid sending galactomannan for patients without risk factors!
  • Other Tests
    • Fungus-specific antigen tests 
      • Ag test for specific fungi like blastomyces, histoplasma, coccidioides, and cryptococcus
      • A few notable cons: cross reactivity between the different endemic infections, and sensitivity is dependent on the timing of the disease course
    • PCR tests
      • Available for Candida (T2Candida) and Aspergillus (Septifast)
      • A few notable cons: no standard methods yet and lack of validation of these PCR assay, these tests are often send-outs only and have a longer turnaround time or barriers to ordering

Pearl 4: Cultures

  • Blood Cultures
    • Sensitivity averages around 50% for invasive candidiasis. A negative result does not rule out infection, especially in high-risk ICU patients.
    • Repeat Testing: Multiple sets increase yield, but if 3 sets are negative, further cultures are often not beneficial.
    • Candida in blood is never a contaminant and typically warrants an ID consult and antifungal therapy.
    • Candida forms strong biofilms on central lines, which may limit shedding into the bloodstream and cause intermittent negatives.
  • Urine Cultures
    • Candida in the urine usually does not indicate invasive disease, particularly in asymptomatic patients.
    •  Unless the patient has textbook UTI symptoms or a recent renal transplant, antifungal therapy is generally not indicated.
  • Sputum and BAL
    • Candida is Typically a Colonizer: Growth of Candida from BAL is very common and almost never indicates invasive lung disease.
    • Cutoff for Galactomannan in BAL: A cutoff >1.0 in BAL fluid is more consistent with true Aspergillus infection; values between 0.5–1.0 may be false positives.
  • “What and Where” Principle: As with all fungal diagnostics, it’s crucial to ask both “what organism?” and “from where?” to determine clinical significance.

Pearl 5: How is invasive fungal disease treated?

  • Azoles
    • Mechanism: Inhibit ergosterol synthesis (a vital component of fungal cell membranes).
    • Examples: Fluconazole, Voriconazole, Posaconazole, Itraconazole, Ketoconazole, Econazole, Isavuconazole
    • Key Points:
      • Fluconazole and ketoconazole primarily cover yeasts (Candida, Cryptococcus).
      • Newer azoles (e.g., voriconazole, posaconazole) also cover molds.
        • Voriconazole, Posaconazole, Isavuconazole all generally cover Aspergillus
        • Posaconazole and Isavuconazole generally cover Mucor as well (but Voriconazole does not)
      • Voriconazole is first-line for probable Aspergillus (per IDSA guidelines).
    • Drug Interactions: Major interactions with calcineurin inhibitors (e.g., tacrolimus), QT-prolonging agents (e.g., methadone), and CYP3A4 substrates (anticonvulsants, DOACs, statins, and many psych meds)
      • Carefully check a patient’s medication list before starting an azole!
    • Side Effects: GI discomfort, elevated LFTs
      • For Voriconazole specifically:  photosensitivity, visual hallucinations, bone pain, hepatitis.
      • Counsel patients to use sun protection during therapy
  • Echinocandins
    • Mechanism: Inhibit β-glucan synthesis, impairing fungal cell wall integrity
    • Examples: Micafungin, Caspofungin, Anidulafungin
    • Key Points:
      • Excellent activity against Candida spp. → First-line for candidemia, especially in ICU or immunocompromised patients.
      • Limited efficacy against molds
  • Polyenes
    • Mechanism: Bind to ergosterol and disrupt fungal cell membrane integrity.
    • Examples: Amphotericin B, Nystatin
    • Key Points:
      • Amphotericin B: First-line for severe fungal infections like cryptococcal meningitis and mucormycosis.
        • Toxicity: nephrotoxicity and infusion reactions.
      • Ambisome (the liposomal form) is strongly preferred at most institutions unless in a resource-limited setting due to less toxicity
      • Nystatin: Used topically or orally (swish & spit) for localized fungal infections (e.g., oral thrush).
  • Remember: Local ecology matters! Be aware of local resistance patterns and ask ID to help guide treatment.
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