What are the causes of elevated beta-D-glucan (Beta-D-Glucan) levels?

From the Guidelines

Elevated beta-D-glucan levels are primarily caused by fungal infections, including invasive candidiasis, aspergillosis, and Pneumocystis jirovecii pneumonia, as well as non-fungal conditions such as hemodialysis, certain antibiotics, and severe bacterial infections. The causes of elevated beta-D-glucan can be broken down into:

• Fungal infections: invasive candidiasis, aspergillosis, and Pneumocystis jirovecii pneumonia are the most common causes of elevated beta-D-glucan levels 1
• Non-fungal conditions:
  • Hemodialysis with cellulose membranes
  • Treatment with certain antibiotics like amoxicillin-clavulanate or piperacillin-tazobactam
  • Use of surgical gauzes containing glucan
  • Administration of blood products (especially immunoglobulins)
  • Severe bacterial infections
  • Mucositis or severe gut inflammation, which can lead to translocation of fungal components from the gut It is essential to consider the clinical context when interpreting beta-D-glucan results, as false positives can occur in up to 15% of cases, particularly in patient populations such as those in an ICU 1. The beta-D-glucan assay has a pooled sensitivity and specificity for diagnosing invasive candidiasis of 75%–80% and 80%, respectively 1. However, the interpretation of these data is complicated by uncertainties about the best cutoff value for a positive result, number of positive tests required to establish a diagnosis, and optimal timing and frequency of testing among at-risk patients 1.

From the Research

Causes of Elevated Beta-D-Glucan

• Invasive fungal infections are a primary cause of elevated beta-D-glucan levels, as seen in patients with proven or probable invasive fungal disease 2, 3, 4, 5, 6
• Serious underlying diseases and conditions, inter-current complications, and intensive care measures can also contribute to elevated beta-D-glucan levels in long-term ICU patients 2
• Bacterial infections, particularly in patients with longer hospitalization, can be a risk factor for invasive fungal infections and subsequent elevation of beta-D-glucan levels 2
• Certain medical treatments and procedures, such as:
  • Use of albumin, intravenous immunoglobulin, and hemodialysis 3
  • Treatment with pegylated asparaginase 6
  • Admission to the intensive care unit (ICU) 6
  • Use of medical devices and parenterally-delivered materials containing beta-D-glucan 5
• Infection with Nocardia sp. can also contribute to elevated circulating beta-D-glucan levels 5
• Translocation of intestinal luminal beta-D-glucan due to mucosal barrier injury can lead to elevated beta-D-glucan levels 5