Table 2.

Potential causes of false positive and false negative results of serum BDG; underlined cases are considered as clinically important and potentially frequent [2,15,16,17,18,19,20,21,22,23,24,25,26,27].

FALSE POSITIVES	Mechanism	Comments
Iatrogenic contamination
Haemodialysis	Use of regenerated cellulose dialysis membrane	Modern dialysis membranes (non-BDG-leaching synthetic membranes) no longer release BDG, and BDG was highly specific for the diagnosis of IFD in the serum of patients receiving haemodialysis in a recent study [27].
Blood and blood derivates such as immunoglobulins and albumin	Cellulosic depth filters are generally mixtures of cellulose and diatomaceous earth and are used to provide initial clarification of blood plasma. Process solutions may also contain BDG and introduce contamination.	The risk of false positivity after receiving blood or blood components seems dependent on the product’s concentrations of BDG and is not constant (for example, never observed in our hospital), while immunoglobulin preparations almost invariably contain BDG [17]. These high titres usually decline rather quickly, and such responses support suspicion of iatrogenic contamination. The depth filters flush strategy was developed to control beta-glucan leaching into the product pool [23].
Cellulose containing gauzes/surgical sponges		The release of BDG from surgery gauzes is temporary and depends on the type of gauze used [25].
Non-glucan-free laboratory equipment		Currently unlikely, since glucan-free laboratory equipment is available.
Beta-lactam antibiotics (e.g., ampicillin-sulbactam, amoxicillin-clavulanate)	BDG may be present in the original source material itself, such as products made by fungal fermentation, in excipients added to the formulation, from media used in microbial or cell culture, or from process equipment, materials, and solutions.	Possible; however, the high level of dilution generated upon injection of relatively low volumes of antibiotic make this unlikely. Further, the high negative predictive value for IFD observed for patients receiving a vast array of antibiotics suggests that this is not a significant problem [20].
Intestinal translocation
Bacteriemia	Translocation as a consequence of ischemic damage to the intestinal barrier due to septic shock	Some experiences suggest that bacteraemia is a very rare source of false positivity [21].
Severe mucositis	Possible translocation of fungal antigens through the intestinal mucosa damaged by chemotherapy	Whether or not this might truly affect specificity of BDG in adult hematologic patients remains controversial, but should be considered in patients with intestinal GvHD or severe mucositis [2].
Major abdominal surgery	Translocation as a consequence of loss of integrity of the intestinal wall	Rare in haematology.
Gut ischemia	Translocation as a consequence of ischemic damage
Burns	Large surface area burns	Validation of alternative cut-offs in specific clinical contexts known to contribute to elevated BDG titre may provide the solution to specificity issues [24]. Unknown if applicable also to severe skin acute GvHD.
Chronic kidney disease	Uremia’s metabolic toxicity
Enterococcus spp. bacteremia	Protease-producing intestinal enterococci
Hepatic function
End-stage liver disease	Reduced clearance
Bacterial infections
Nocardia spp. infection		Although rare, needs to be considered in differential diagnosis in case of compatible clinical presentation (pulmonary, cerebral) [15].
Streptococcus pneumoniae Type 37	Producing a BDG with a (1→3)-β-backbone [15]
Pseudomonas spp.	Producing (1→2)-β-linked glucan sequences [15]
Interference
Pegylated asparaginase	Drug-related alterations in heme metabolism, which in turn interfere with measurement of BDG in serum [2]
Haemolysis	Interference with test procedure.	Possible interference, particularly for colorimetric assays [22].
FALSE NEGATIVES
Antifungal prophylaxis and therapy	Low pre-test probability of IFI	Lower median BDG values were reported in breakthrough IFI episodes [16]. BDG should be used to exclude rather than for diagnosis in these patients [18].
Sanctuary sites or poorly vascularized sites of infection	BDG not released into blood
Candida parapsilosis or Candida auris	Lower content of BDG component in fungal wall	Lower levels of BDG reported [19,26].
Hyperbilirubinemia	Interference with test procedure	Possible interference, particularly for colorimetric assays [22].