Cefepime and Elevated Beta-D-Glucan: Frequency Unknown but Clinically Significant
The exact percentage of patients receiving cefepime who develop elevated beta-D-glucan levels has not been quantified in published literature, but cefepime is explicitly recognized as a cause of false-positive beta-D-glucan results and should always be considered when interpreting elevated levels in patients receiving this antibiotic. 1
Evidence for Cefepime-Associated False Positives
The German Society of Hematology and Medical Oncology guidelines explicitly identify cefepime as one of several semisynthetic β-lactam antibiotics that can produce false-positive results on both galactomannan and beta-D-glucan testing. 1
Cefepime is grouped alongside other β-lactams known to cause false positives, including amoxicillin-clavulanate, piperacillin-tazobactam, carbapenems, and ceftriaxone. 1
Among these β-lactams, intravenous amoxicillin-clavulanate and piperacillin-tazobactam are particularly well-documented causes of false-positive beta-D-glucan results. 1
Clinical Implications When Interpreting Beta-D-Glucan in Cefepime-Treated Patients
Immediate Assessment Steps
Do not initiate antifungal therapy based solely on a single elevated beta-D-glucan result in a patient receiving cefepime without supporting clinical or microbiological evidence. 1
Obtain a second beta-D-glucan test within 3-5 days to determine if results are consistently positive, as two consecutive positive results significantly improve specificity compared to a single positive test. 1
Evaluate for additional confounding factors that commonly cause false positives: gram-positive or gram-negative bacteremia, hemodialysis, receipt of albumin or intravenous immunoglobulin products, exposure to surgical gauze, mucositis or gastrointestinal mucosal disruption, and fungal colonization without invasive disease. 1
Risk Stratification for True Invasive Fungal Infection
Assess whether the patient has high-risk features that increase the likelihood of true invasive fungal infection despite cefepime use:
- Neutropenia or hematologic malignancy 1
- Hematopoietic stem cell or solid organ transplantation 1
- Prolonged ICU stay with multiple risk factors 1
- Recent abdominal surgery with complications 1
- Persistent fever despite broad-spectrum antibiotics 1
Complementary Diagnostic Testing
- Obtain at least two sets of blood cultures from different sites 1
- Perform serum galactomannan testing if aspergillosis is suspected 1
- Obtain high-resolution chest CT if pulmonary involvement is suspected 1
- Collect site-specific cultures from normally sterile sites when clinically indicated 1
When to Empirically Treat Despite Potential False Positive
Start empiric antifungal therapy while awaiting repeat testing only in these specific scenarios:
- Critically ill patient with septic shock and high clinical suspicion for invasive candidiasis 1
- Neutropenic patient with persistent fever despite broad-spectrum antibiotics and high-risk features 1
- Clinical deterioration with radiographic findings suggestive of invasive fungal infection 1
The preferred empiric regimen for suspected invasive candidiasis is an echinocandin: caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily. 1
Critical Pitfall to Avoid
Remember that beta-D-glucan has a high negative predictive value (>90%), so a negative result is useful for ruling out invasive fungal infection. 1 However, the test does not detect mucormycosis (zygomycetes) or most Cryptococcus species. 1