What can cause a falsely elevated serum (1→3)-β-D-glucan level?

Causes of Falsely Elevated Beta-1,3-D-Glucan (BDG)

Intravenous immunoglobulin (IVIG) administration is the most clinically significant cause of false-positive BDG results, with elevations persisting for up to 3 weeks post-infusion. 1

Primary Causes of False-Positive BDG

Blood Products and Immunoglobulins (Most Common)

• IVIG preparations cause false-positive BDG in the vast majority of patients, with levels potentially remaining elevated for more than 2 weeks and normalizing only by 3 weeks post-administration 2
• Therapeutic monoclonal antibodies are associated with high rates of false-positive BDG in onco-hematological patients 3
• Product-specific effects: Privigen shows particularly strong association with elevated BDG (large effect size, Cohen's dz = 0.92), while other products like Venoglobulin and Venilon-I show minimal impact 4
• Packed red blood cells (PRBC) can dramatically increase BDG levels (e.g., from 13-17 pg/mL to 183-361 pg/mL) 5
• Human albumin causes modest BDG elevations 5
• Fresh frozen plasma (FFP) tests positive for BDG content 5

Clinical Pearl: BDG should not be used to diagnose invasive fungal disease within 3 weeks after IVIG administration 2. The BDG concentration in blood products directly predicts post-transfusion false-positive results 5.

Bacterial Infections

• Gram-negative bacteremia causes false-positive BDG in 59% of cases, with significantly higher BDG levels compared to Gram-positive infections 6
• Pseudomonas bloodstream infections specifically elevate BDG 1
• E. coli polysaccharides can cross-react with BDG assays 1
• Streptococcus pneumoniae bacteremia does NOT cause false-positive results 6

Medical Materials and Contamination

• Glucan-containing gauze exposed to blood or serosal surfaces causes persistent false-positive results 1, 7, 8
• Medical sterile gauze, cotton swabs, and cotton balls contain high BDG concentrations and represent an important but often overlooked source of contamination 8
• Cellulose-containing materials: hemodialysis membranes and blood product filters can introduce BDG 7

Other Causes

• Certain intravenous antimicrobials may contain trace BDG 7
• Fungal preparations used therapeutically 8

Important Caveats

What BDG Does NOT Detect

BDG is typically negative in:

• Mucormycosis (Mucorales lack significant BDG in cell walls) 1
• Cryptococcosis 1
• Blastomycosis 9

Cross-Reactivity (True Positives, Not False Positives)

BDG is legitimately positive in non-Candida/Aspergillus infections including:

• Pneumocystis jirovecii 1, 9
• Histoplasma
• Fusarium
• Other hyaline molds

These represent true positives reflecting actual fungal cell wall components, not false elevations.

Diagnostic Approach When BDG is Unexpectedly Elevated

1. Review recent transfusions: Check for IVIG, therapeutic antibodies, PRBC, albumin, or FFP within the past 3 weeks
2. Assess for bacterial infections: Particularly Gram-negative bacteremia or Pseudomonas
3. Examine specimen collection: Look for contamination from gauze, cotton materials, or cellulose-containing products
4. Consider hemodialysis: Cellulose membranes are a known source
5. Review medications: Check for IV antimicrobials or fungal preparations
6. Integrate clinical context: Persistent elevation despite clinical improvement and negative cultures should prompt investigation of false-positive causes 8

Critical Point: When microbiological evidence is insufficient and clinical symptoms improve with clear therapeutic response, yet BDG remains persistently positive at high levels, systematic exclusion of these false-positive causes is essential before continuing antifungal therapy 8.