Which fungal infection would likely have a negative serum (1,3)-beta-D-glucan assay, invasive aspergillosis, invasive candidiasis, pneumocystic jirovecii infection, or mucormycosis?

Serum (1,3)-Beta-D-Glucan Assay in Fungal Infections

Mucormycosis is the only fungal infection among those listed that would have a negative serum (1,3)-beta-D-glucan assay result. 1, 2

Diagnostic Value of (1,3)-Beta-D-Glucan Testing

Mechanism and Coverage

• (1,3)-Beta-D-glucan is a cell wall component found in most pathogenic fungi, but with notable exceptions:
  • Present in: Aspergillus, Candida, and Pneumocystis jirovecii 3, 4
  • Absent in: Mucorales (the causative agents of mucormycosis) and Cryptococcus neoformans 3

Specific Fungal Infections and BDG Results

Mucormycosis

• The cell wall of Mucorales fungi lacks significant amounts of (1,3)-beta-D-glucan 1
• In vitro analysis of culture supernatants from different Mucorales species showed low antigen reactivity compared to other molds 1
• Multiple studies have confirmed negative (1,3)-beta-D-glucan results in patients with mucormycosis 1, 2
• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) guidelines explicitly state that "(1,3)-beta-D-glucan is a common component of the cell wall of a wide variety of fungi but not of the Mucorales" 1
• The guidelines rate (1,3)-beta-D-glucan testing as "D" level recommendation (not recommended) for mucormycosis diagnosis 1

Invasive Aspergillosis

• (1,3)-Beta-D-glucan is present in the cell wall of Aspergillus species 3
• BDG testing appears to be more sensitive than galactomannan detection in patients with invasive aspergillosis 3
• Median initial BDG values in invasive aspergillosis are typically >500 pg/mL 4

Invasive Candidiasis

• Candida species contain (1,3)-beta-D-glucan in their cell walls 3, 4
• BDG testing has approximately 81% sensitivity for invasive candidiasis 2
• Median initial BDG values in invasive candidiasis are typically around 136 pg/mL 4

Pneumocystis jirovecii Infection

• Pneumocystis jirovecii contains significant amounts of (1,3)-beta-D-glucan 3
• BDG testing is highly sensitive for Pneumocystis pneumonia 4
• Median initial BDG values in PCP are typically >500 pg/mL 4

Clinical Implications and Diagnostic Approach

• When evaluating a patient with suspected invasive fungal infection and negative BDG test:

  • Consider mucormycosis, especially if galactomannan tests are also negative but radiological findings suggest invasive fungal disease 1, 2
  • Direct microscopy, culture, and histopathology remain the primary diagnostic methods for mucormycosis 1, 2

• False positives can occur with:

  • Hemodialysis with cellulose membranes
  • Treatment with immunoglobulin or albumin
  • Blood products filtered through cellulose filters
  • Certain intravenous antimicrobials 3, 5

Summary

Among invasive aspergillosis, invasive candidiasis, Pneumocystis jirovecii infection, and mucormycosis, only mucormycosis would consistently yield a negative serum (1,3)-beta-D-glucan assay result due to the absence of this cell wall component in Mucorales fungi.