Infectious Diseases II
Up to 50% of patients with histopathologically proven invasive candidiasis have negative blood cultures.
Biopsies are often not feasible in critically ill patients.
Surrogate markers of fungal infections are needed for early diagnosis and to avoid delays in treatment,
which have been associated with worsened outcomes.
Ξ²-d-Glucan
Found in the cell membrane of most fungal pathogens (except for Mucor and Cryptococcus).
Potentially a screening tool for Candida, Aspergillus, and Pneumocystis.
Fungitell assay can detect Ξ²-d-glucan in serum and provide results within 2 hours.
Variable cutoffs are described in the literature for a positive result. A suggested cutoff for positive
results, as used in a recent study evaluating prophylactic and preemptive antifungal therapy in
critically ill patients, is greater than 80 pg/mL.
| d. | Considerable differences in sensitivity and specificity values have been seen in different populations. |
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Consistently high negative predictive values and low positive predictive values have been seen
for the diagnosis of invasive fungal infections, which suggests that it is best used as a screening-
out tool when the values are low. Low positive predictive value may occur because many clinical
scenarios could lead to false-positive results.
Exposure to Ξ²-d-glucanβcontaining surgical supplies and topical products
ii.
Colonization with Candida
iii.
Thrush and mucositis
iv.
Cellulose membranes from dialysis filters
Bacterial infections
vi.
Receipt of Ξ²-lactam antibiotics, albumin, or immunoglobulins
When used as a tool to potentially initiate treatment, optimal results occur when two consecutive
tests are positive.
Nonspecific fungal element makes interpretation difficult. May detect elements from Aspergillus,
Candida, and Pneumocystis. Does not detect different species.
Has been evaluated in combination with clinical prediction scores for invasive candidiasis
in critically ill patients for initiating empiric antifungal therapy. When using Ξ²-d-glucan as a
screening tool, empiric echinocandin therapy does not result in any significant differences in
clinical outcomes compared with placebo.
A recent multicenter, randomized controlled trial found no difference in 28-day mortality
when antifungal treatment was guided by Ξ²-d-glucan compared with control where initiation of
T2 magnetic resonance
Nanodiagnostic approach, which detects amplified Candida DNA. Similar to traditional MRI
techniques, but done on a micro scale.
Performed on whole blood, where magnetic particles that are coated with agents specific for binding
to Candida DNA.
When Candida is present in whole blood, it will bind to the particles and cluster, causing microscopic
disruptions in the magnetic fields.
| d. | Currently, FDA approved for 5 pathogenic Candida species (C. albicans, C. glabrata, C. |
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parapsillosis, C. tropicalis, C. kruseii)
High sensitivity (91%) and specificity (98%) but lacks clinical study application
Mannan/Anti-mannan
Mannan is a polysaccharide component of the fungal cell wall that is specific to Candida spp.
A commercially available latex agglutination and enzyme immunoassay exists for both mannan
antigen and anti-mannan antibibodies that develop in response to mannan.