What blood tests are recommended for diagnosing a suspected fungal infection?

Blood Tests for Diagnosing Suspected Fungal Infections

For suspected invasive fungal infections, obtain serum galactomannan (GM) testing as the first-line blood test, performed at least twice weekly in high-risk immunocompromised patients, with serum (1→3)-β-D-glucan (BDG) as a complementary test when GM is negative but clinical suspicion remains high. 1, 2

Primary Blood Tests by Clinical Context

For Suspected Invasive Aspergillosis (Most Common Scenario)

Serum Galactomannan (GM):

• This is the gold standard first-line blood test with sensitivity of 71% and specificity of 89% at an optical density index cutoff of 0.5 on two consecutive samples 1
• Must be performed at least 2 times per week due to transient circulation of GM in serum 1
• Has a very high negative predictive value (>90%) for ruling out invasive aspergillosis 1
• Critical caveat: A single negative test does NOT rule out infection—serial monitoring every 3-4 days is essential in high-risk patients 3

Serum (1→3)-β-D-Glucan (BDG):

• Use as a complementary test, NOT as the sole diagnostic test 2, 3
• Sensitivity ranges from 50-70% and specificity 91-99% in hematological malignancy patients 2
• Detects multiple fungal species (Candida, Aspergillus, Pneumocystis, Fusarium) but NOT Zygomycetes or Cryptococcus 3
• Major limitation: Low specificity means it should never be relied upon alone for diagnostic decision-making 2, 3

For Suspected Invasive Candidiasis in ICU Patients

Serum β-D-Glucan:

• Sensitivity of 81% and specificity of 60% for invasive candidiasis or candidemia in critically ill patients 4
• Higher cutoff values increase specificity but reduce sensitivity 2
• High negative predictive value (85-92%) makes it useful for excluding disease in ICU patients 2

For Endemic Mycoses (Histoplasmosis, Blastomycosis, Coccidioidomycosis)

Serum Antibody Testing:

• Pathogen-specific antibody testing is recommended for suspected endemic mycoses 2
• Serial testing with close follow-up is necessary in patients from endemic areas with suspected community-acquired pneumonia 2

Molecular Blood Tests

Aspergillus PCR (Blood or Serum):

• Recommended in severely immunocompromised patients with suspected invasive pulmonary aspergillosis 2, 1
• Sensitivity of 81% and specificity of 79% for blood/serum samples 4
• Can detect fungal DNA even after antifungal treatment has been initiated 2
• Important limitation: Lack of standardization across laboratories means it's not yet included in mandatory recommendations 2

Pan-Fungal PCR:

• Targets conserved fungal DNA regions (18S rRNA, 28S rRNA, or ITS) 2, 1
• Sensitivity ranges from 65-100% and specificity 65-75% depending on methodology 2
• Particularly valuable when the causative pathogen is unknown in immunocompromised patients 2
• Must be used in combination with other diagnostic methods for optimal results 1

Critical Pitfalls to Avoid

False-Positive Galactomannan Results:

• Piperacillin-tazobactam and other β-lactam/β-lactamase combinations cause false positives 3
• Chemotherapy or mucositis may lead to false positives from cross-reactive epitopes 3

False-Negative Galactomannan Results:

• Mold-active antifungal prophylaxis or therapy significantly reduces sensitivity 3

False-Positive β-D-Glucan Results:

• Early ICU admission, concurrent bacterial infections, certain hemodialysis filters, beta-lactam antimicrobials, and immunoglobulin administration can all cause false positives 2, 5

Single Test Limitations:

• The sensitivity of a single-serum fungal antigen test is low, particularly in patients receiving antifungal agents 6
• Never rely on a single negative test to rule out invasive fungal infection—serial testing and combination of tests are required 1

Optimal Diagnostic Algorithm

1. Start with serum GM testing twice weekly in all high-risk immunocompromised patients with suspected invasive aspergillosis 1

2. Add serum BDG for complementary information, especially if GM is negative but clinical suspicion remains high 2, 1

3. Consider Aspergillus PCR on blood samples in severely immunocompromised patients 2, 1

4. If blood tests are negative but clinical suspicion is high, proceed to bronchoscopy with bronchoalveolar lavage (BAL) for GM BAL testing (sensitivity 84%, specificity 88%) 1

5. Combination testing provides the best diagnostic accuracy: GM (BAL) with BDG (serum) shows sensitivity of 92%, specificity of 93%, with diagnostic odds ratio of 153.0 1

Special Considerations for Immunocompromised Patients

• Blood cultures should be obtained in neutropenic patients with skin lesions, as they may harbor resistant microbes, yeast, or molds 6
• Multiple diagnostic tests should be performed simultaneously in immunocompromised patients with hematological malignancies due to high mortality risk 2
• Antibody testing against Aspergillus is often not detected in immunocompromised patients, making it useless for acute diagnosis 1