Can cefepime (Cefepime) cause a false positive beta-D-glucan test result?

Cefepime and False-Positive Beta-D-Glucan Results

Yes, cefepime can cause false-positive beta-D-glucan test results, and this should 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 This occurs alongside other β-lactams including:

• Amoxicillin-clavulanate 1
• Piperacillin-tazobactam 1, 2
• Carbapenems 1
• Ceftriaxone 1

Mechanism and Clinical Significance

The false positivity results from beta-D-glucan contamination present in the antimicrobial formulations themselves. 3 A comprehensive analysis of 35 antimicrobial drugs found that 25 substances (including 20 antibiotics and all tested antifungals) contained sufficient beta-D-glucan to trigger positive test results, with concentrations ranging from 9 to 2,818 pg/mL depending on the specific drug. 3

The clinical impact can be substantial:

• Penicillin G administration at 24 million units daily caused serum beta-D-glucan levels to rise to 81.0 pg/mL, which decreased to 38.0 pg/mL within 14 hours of discontinuation 4
• The amount of beta-D-glucan detected in serum correlated directly with the actual beta-D-glucan concentration measured in antibiotic vials 4

Interpretation Strategy When Cefepime is Present

Do not initiate antifungal therapy based solely on a positive beta-D-glucan result in patients receiving cefepime without additional supporting evidence. 2, 5 Instead:

Immediate Actions:

• Repeat beta-D-glucan testing within 3-5 days to determine if results remain consistently positive 2
• Two consecutive positive results significantly improve specificity compared to a single test 2
• Obtain blood cultures (minimum two sets from different sites) 2, 5
• Perform serum galactomannan testing if aspergillosis is suspected 2
• Order high-resolution chest CT if pulmonary fungal infection is considered 2

Risk Stratification:

Assess whether high-risk features for true invasive fungal infection are present:

• Neutropenia or hematologic malignancy 2
• Hematopoietic stem cell or solid organ transplantation 2
• Prolonged ICU stay with multiple risk factors 2
• Recent abdominal surgery with complications 2
• Persistent fever despite broad-spectrum antibiotics 2

Additional Confounding Factors to Consider

Beyond cefepime exposure, evaluate for other causes of false-positive beta-D-glucan results that may coexist:

• Gram-positive or gram-negative bacteremia (59% false-positive rate with gram-negative bacteremia) 2, 6
• Hemodialysis 1, 2, 5
• Albumin or intravenous immunoglobulin administration 1, 2, 5
• Surgical gauze or glucan-containing materials 2
• Mucositis or gastrointestinal mucosal disruption 2

When to Initiate Empiric Antifungal Therapy Despite Cefepime Use

Start empiric echinocandin therapy while awaiting confirmatory testing only if:

• Patient is critically ill with septic shock AND high clinical suspicion for invasive candidiasis 2
• Patient is neutropenic with persistent fever despite broad-spectrum antibiotics AND high-risk features 2
• Clinical deterioration occurs with radiographic findings suggestive of invasive fungal infection 2

The preferred empiric regimen 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). 2, 5

Critical Pitfall to Avoid

The high negative predictive value (>90%) of beta-D-glucan remains reliable even in patients on cefepime. 5, 7 A negative result effectively rules out invasive fungal infection and can be used to discontinue unnecessary antifungal therapy or avoid its initiation. 7