BDG Levels Research Articles

Experience with β-D-Glucan Assay in the Management of Critically ill Patients with High Risk of Invasive Candidiasis: An Observational Study.

Background:The (1,3)-β-D-glucan assay (BDG) is recommended for the early diagnosis of invasive candidiasis (IC).Methods:Records of 154 critically ill adults with suspected IC, on whom BDG was done, were analyzed. Patients were divided into three groups: Group A (confirmed IC), Group B (alternative diagnosis or cause of severe sepsis), and Group C (high candidal score and positive BDG [>80 pg/mL] but without a confirmed diagnosis of IC).Results:Mean BDG levels were significantly higher in Group A (n = 32) as compared to Group B (n = 60) and Group C (n = 62) (448.75 ± 88.30 vs. 144.46 ± 82.49 vs. 292.90 ± 137.0 pg/mL; P < 0.001). Discontinuation of empiric antifungal therapy based on a value <80 resulted in cost savings of 14,000 INR per day per patient.Conclusion:A BDG value of <80 pg/ml facilitates early discontinuation of empirical antifungal therapy, with considerable cost savings.

False positive serum levels of (1–3)-ß-D-Glucan after infusion of intravenous immunoglobulins and time to normalisation

(1-3)-ß-D-Glucan (BDG) is a marker for invasive fungal diseases (IFD). Administration of intravenous immunoglobulin preparations (IVIG) has been reported to lead to false positive BDG serum levels >80pg/ml. The aim of the study was to determine the time interval between IVIG infusion and normalisation of BDG serum levels. In 22 paediatric haemato-/oncologic patients, we analysed 92 BDG serum levels obtained within 4 weeks after IVIG administration (0.5 to 1g/kg body weight), correlated them to 54 IVIG episodes and compared them to 76 BDG levels obtained in 29 patients without IVIG administration in the 4 weeks prior to BDG analyses (control group). BDG peak levels within 3 days after IVIG ranged from 21.47 to 660.38 (median 201.4) pg/ml. BDG serum levels at 7, 14 and 21 days (+/-1 day each) after IVIG infusion were significantly higher than BDG serum levels in the control group (p<0.001 each). By days 7, 14, and 21 (+/-1 day each) after IVIG infusion, BDG serum levels have normalized (<80pg/ml) in 64.0%, 76.5% and 100%, respectively. IVIG administration leads to false positive BDG levels in the vast majority of patients. Elevated BDG levels may be detectable for more than two weeks after IVIG administration, while BDG levels normalized within 3 weeks in all patients. Therefore, BDG should not be used to diagnose IFD within three weeks after IVIG administration.

Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis

Background Central nervous system (CNS) histoplasmosis is a life-threatening condition, and represents a diagnostic and therapeutic challenge. Although CSF (1,3)-β-d-glucan (CSF BDG) is available as a biologic marker for diagnosis of fungal meningitis, there are limited data on its use for diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection using the Fungitell assay in patients with CNS histoplasmosis and controls.Methods Patients were classified as cases if there was CNS inflammation (CSF WBC ≥ 5 mm3/ml) plus laboratory confirmation of H. capsulatumin CNS samples or from extra-CNS sites with no alternative etiology for CSF pleocytosis. Controls were patients with histoplasmosis but no evidence of CNS involvement, an alternative diagnosis, or other fungal meningitis.ResultsIn total, 47 cases and 153 controls were evaluated (Table 1). Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. CSF BDG was positive in 25 (53.2%) cases using a level of ≥80 pg/ml, the median CSF BDG level was 140.5 pg/ml (range from <31 to 500 pg/ml). The detection of CSF BDG level ≥80 pg/ml was not associated with positive CSF Histoplasma antigen (P = 0.28) or positive CSF Histoplasma culture (P = 0.56). The sensitivity for detection of CSF BDG was 53.2% and the specificity was 87.3%, compared with 78.7% (P = 0.009) and 96.4% (P = 0.003), respectively, for detection of antigen. CSF BDG was positive in 20 of 153 (13.1%) patients in the control group. Seven of 11 (63.6%) other CNS fungal meningitis cases (five Cryptococcus, two Aspergillus, two Blastomyces, one Candida, and one suspected fungal meningitis) had CSF BDG ≥80 pg/ml.Conclusion A positive CSF BDG supports the diagnosis of fungal meningitis but cannot distinguish among the different etiologies. The sensitivity and specificity of detection of CSF BDG was lower than that of antigen detection.Table 1:Characteristic of the study patientsParameterCNS histoplasmosisControlsa P-valueImmunocompromised23/47 (48.9%)67/153 (43.8%)0.54CSF BDG > 80 pg/ml25/47 (53.2%)b20/153 (13.1%)c<0.0001CSF Histoplasma antigen positive37/47 (78.7%)25/142 (3.5%)3<0.0001CSF culture positive9/44 (20.5%)11/117 (9.4%)0.058 aControl included five Cryptococcus, two Aspergillus, two Blastomyces, one Candida, and one suspected fungal meningitis. b P-value = 0.009; cP-value = 0.003.Disclosures L. J. Wheat, MiraVista: President and owner, equity and Salary

High level of β-(1,3)-d-glucan antigenaemia in cystic fibrosis in the absence of invasive fungal disease

β-(1,3)-d-glucan (BDG) is used to rule out invasive fungal disease (IFD) but its usefulness in cystic fibrosis (CF) has not been evaluated. We measured serum BDG in CF patients with no clinical suspicion of IFD. Samples from 46 adult CF patients during a stable period and during pulmonary exacerbation were tested. The association of BDG with clinical variables was analyzed. Three hundred and three non-CF patients with suspected IFD were used as comparators. Both samples were negative in 52% of CF patients, whereas 67% of comparators had only negative results (P=0.08). CF patients with pancreatic insufficiency and CF-related diabetes had fewer negative results (P<0.05 for both). Negative results were more common in older CF patients (P<0.05). Use of antibiotics, presence of fungi in sputum and CF liver disease did not impact BDG levels. In conclusion, patients with CF experience significant BDG antigenaemia in the absence of IFD.

Experience with β-d-Glucan Assay for Diagnosis of Invasive Candidiasis in ICU Patients: Pilot Study from India

Backgroundβ-d-Glucan assay (BDG) has been recently introduced in India and is recommended for the early diagnosis of invasive candidiasis (IC), but there are a number of factors (eg β-lactam antibiotics, immunoglobulin and albumin infusions, bacteremia and surgical mesh) which may falsely elevate BDG levels.MethodsThis was a retrospective, observational study done in the 23 bedded multi-disciplinary ICU of a tertiary care hospital in South India. Case records of adult (> 18 years) non-neutropenic patients having severe sepsis or shock with ≥ 1 risk factor for IC were analyzed. As a standard practice, BDG assay was sent and effective antifungals were started on the day of suspicion of IC. All neutropenic, immunocompromised patients, those already on antifungal and those who were diagnosed with other invasive fungal infections were excluded from the study. FDA approved Fungitell assay was used to measure serum BDG levels (pg/mL).ResultsPatients were divided into 3 groups. Group A (n = 16) comprised of patients in whom diagnosis of IC was confirmed (blood culture or another sterile site grew candida). Group B (n = 30) comprised of patients in whom alternative diagnosis of severe sepsis or septic shock was found or they did not improve after administration of antifungals. Group C (n = 31) comprised of those patients in whom neither diagnosis of IC was confirmed nor an alternative explanation was found but they improved clinically on giving antifungal therapy. Mean BDG levels was significantly higher in Group A as compared with Group B and Group C (448.75 ± 88.30 vs 144.46 ± 82.49 vs 292.90 ± 137.0 pg/mL; P < 0.001). The mean value of the BDG was higher than the accepted cutoff of 80 pg/mL in all three groups (Figure 1). The use of agents which cause false elevation of BDG was significantly higher in Group B as compared with Group A (P = 0.02).ConclusionA BDG assay cutoff of 80 pg/mL leads to a higher number of false positive results in ICU patients, where false positive factors are unavoidable. The results of this study suggest that a higher cutoff of at least 144 pg/mL will be more specific for IC, although this may need further validation with larger trials.Figure 1:Mean BDG values in various groupsDisclosures All authors: No reported disclosures.

Utility of Serial β-d-Glucan Levels in Patients with High Risk for Invasive Candidiasis: A Potential Tool for Antifungal Stewardship

BackgroundInvasive candidiasis (IC) is a severe infection in which diagnosis is challenging and often made late in the course of infection. Patients with delayed initiation of antifungals have high mortality risk; physicians tend to start empiric therapy at earliest clinical suspicion of IC. Excessive use of antifungals worsens selection pressure for resistance. Thus, alternative ways to aid antifungal stewardship are highly relevant. We aimed to evaluate performance of (1–3)-β-d-glucan (BDG) serial testing for antifungal stewardship to improve antifungal prescribing and to stop unnecessary use without compromising care.MethodsThis was a prospective observational study on patients at high risk of IC. Adults with recent intra-abdominal surgery, admitted to surgical intensive care unit (ICU), and prescribed an antifungal for suspected IC were included. Blood samples were taken at start of and days 3, 7, 10, 14, and weekly thereafter until antifungal is stopped, for BDG quantification with Fungitell assay. Medical records were reviewed for patient characteristics, antifungal regimen and outcomes. BDG was evaluated against clinical and microbiological outcomes. Sensitivity, specificity, positive and negative predictive values of BDG and Candida score were evaluated.ResultsWe included 15 patients and 74 BDG levels. Patients with confirmed IC from cultures had a median BGD of >500 pg/mL and candida score of 3, compared with 55.5 pg/mL and score of 2 in those without confirmed IC. BGD assay anticipated diagnosis of IC with a sensitivity and specificity of 100% and 66.7%, with a positive and negative predictive value of 62.5% and 100% respectively. Of the five patients with confirmed IC, two had declining BDG, corresponding to clinical response to therapy. Their BDG were <80 pg/mL on day 7 and 14 of therapy, respectively, and were disharged from ICU, but one later had septic shock with Klebsiella pneumoniae bacteremia and demised. Repeat fungal cultures were negative. The remaining three had persistently high BGD of >500 pg/mL and eventually demised. No obvious trend was observed in those without confirmed IC.ConclusionWe were able to characterise BDG levels in patients at high risk of IC. There is utility in BGD serial testing as a tool for antifungal stewardship, however more data is required to confirm findings.Disclosures All authors: No reported disclosures.

1,3-ß-d-Glucan testing is highly specific in patients undergoing dialysis treatment

The aim of this combined in-vitro and in-vivo study was to investigate whether state of the art dialysis modalities produce false positive serum 1,3-ß-d-Glucan (BDG) levels. Dialysis fluid for simulated dialysis treatments was spiked with BDG from different sources. Samples were taken from the dialysate and dialyzer blood compartments at various time points. In addition, serum samples were obtained in three groups of patients without invasive fungal disease: a.) twelve patients on chronic hemodialysis (HD)/hemodiafiltration (HDF); b.) ten patients on continuous ambulatory peritoneal dialysis (CAPD); and c.) ten patients with stable chronic kidney disease (CKD) but without dialysis. Median BDG levels in BDG spiked dialysate were 3250.9, 2050.4, and 390.1pg/ml respectively. All corresponding samples from the blood compartments were BDG negative. In HD/HDF patients no increase of serum BDG levels could be observed over the duration of treatment. 71/72 BDG tests in this group remained negative. BDG tests were also negative in 9/10 CAPD patients, both in in- and outflow dialysates as well as in all ten patients with CKD. We conclude that state of the art renal replacement therapies using up-to-date treatments are not a cause of falsely elevated serum BDG levels.

(1→3)-β-d-Glucan: A Biomarker for Microbial Translocation in Individuals with Acute or Early HIV Infection?

The extent of gut microbial translocation, which plays roles in HIV disease progression and non-AIDS comorbidities, appears to vary with the composition of the gut microbiome, particularly the presence of Lactobacillales, which reduce mucosal injury. While low proportions of Lactobacillales in the distal gut microbiome are a very promising indicator of microbial translocation, measurement is expensive and complicated and not feasible for clinical routine. (1→3)-β-d-Glucan (BDG) is a component of most fungal cell walls and might be a surrogate marker for Lactobacillales proportion in the gut and a useful indicator of HIV-associated gut injury. This study evaluated BDG as a biomarker of gut integrity in adults with acute or early HIV infection (AEH). Study samples were collected longitudinally during study visits at weeks 0, 12, and 24 in a cohort of 11 HIV-infected men starting antiretroviral therapy during AEH. Blood plasma levels of BDG, soluble cluster of differentiation 14 (sCD14) and lipopolysaccharide (LPS) were measured and then correlated with the proportion of Lactobacillales in the distal gut microbiome, as measured by 16s rDNA sequencing by using mixed-effects models with random intercepts. Mean BDG and sCD14 levels across subjects were associated with Lactobacillales after controlling for time effects and within-subjects correlations (p-values < 0.05), while LPS levels were not. Specifically, each point increase in mean BDG and sCD14 levels across participants was associated with 0.31 ± 0.14 and 0.03 ± 0.01 percent decrease in mean Lactobacillales proportions, respectively. BDG and sCD14 may be indicators of low Lactobacillales in the gut in adults with acute or early HIV infection, and serve as biomarkers of gut integrity and microbial translocation in HIV infection. Larger studies are needed to confirm our findings.

Lower sensitivity of serum (1,3)-β-d-glucan for the diagnosis of candidaemia due to Candida parapsilosis

The aim of this study was to evaluate the sensitivity and the levels of 1,3-β-d-glucan (BDG) among patients with candidaemia due to different Candida species. Retrospective study of all patients who had a single-species candidaemia and BDG testing performed within 48 h from the onset of candidaemia during 2009–2015 was performed. Factors influencing the sensitivity of BDG, including the presence of a central venous catheter, antifungal therapy and Candida species, were analysed in univariate and multivariate models. In all, 107 patients with the following Candida distribution were included: 46 (43%) Candida albicans, 37 (35%) Candida parapsilosis, and 24 (22%) other species. BDG sensitivity and levels were the highest in C. albicans candidaemia and lowest for C. parapsilosis (respectively, 72% and 410 pg/mL for C. albicans, 41% and 39 pg/mL for C. parapsilosis, and 63% and 149 pg/mL for other species; p 0.015 and p 0.003). In multivariate analysis, Candida species (parapsilosis versus others) was the only factor influencing the sensitivity of BDG (OR 0.3, 95% CI 0.1–0.7, p 0.006). The sensitivity of BDG in candidaemia seems highly dependent on the fungal species, with the lowest being for C. parapsilosis.

Diagnostic performance of 1,3-beta-D-glucan serum screening in patients receiving hematopoietic stem cell transplantation.

The polysaccharide cell wall component, 1,3-beta-D-glucan (BDG), is used as a serum biomarker for invasive fungal infection (IFI). Patients receiving hematopoietic stem cell transplantation (HSCT) are considered a highly vulnerable group for IFI development. We evaluated the diagnostic performance of serum BDG screening in HSCT recipients. HSCT recipients were prospectively enrolled in this study between September 2014 and August 2015. Routine serum BDG screening was performed 2-3 times weekly by using the Fungitell(®) assay. All samples were classified according to the 2008 EORTC/MSG criteria, with serum BDG results not being considered for classification. The diagnostic performance of BDG testing for IFI was calculated. BDG values ≥80 pg/mL were considered positive. A total of 308 serum samples were collected in 45 patients. The majority of 172 samples (55.8%) were obtained at the early phase (within 30 days) after allogeneic HSCT. BDG levels were significantly higher in 16 possible/probable IFI samples when compared to no evidence for IFI samples (median 170 pg/mL, interquartile range [IQR] 100-274 pg/mL vs. median 15 pg/mL, IQR 15-15 pg/mL; P < 0.001, Mann-Whitney U-test). Diagnostic performance of serum BDG screening for possible IFI/probable invasive pulmonary aspergillosis vs. no evidence for IFI was as follows: sensitivity 81%, specificity 98%, positive predictive value 65%, negative predictive value (NPV) 99%, and diagnostic odds ratio 176 (95% confidence interval 41-761). Our data suggest that serum BDG testing in HSCT patients may be highly specific and associated with a very high NPV of >99%. Therefore, serum BDG may be a helpful tool to rule out IFI in HSCT patients.

(1→3)-β-D-Glucan Levels Correlate With Neurocognitive Functioning in HIV-Infected Persons on Suppressive Antiretroviral Therapy: A Cohort Study.

Microbial translocation from the gut is associated with immune dysfunction, persistent inflammation, and likely plays a role in the pathogenesis of neurocognitive dysfunction during HIV infection. (1→3)-β-D-Glucan (BDG) is a component of most fungal cell walls and might be a useful indicator of gut mucosal barrier impairment. The objective of this study was to evaluate whether higher blood BDG levels correlate with impaired neurocognitive functioning in a cohort of HIV-infected adults with suppressed levels of HIV RNA in blood plasma.In this cross-sectional cohort study, we measured levels of BDG in blood plasma and cerebrospinal fluid (CSF) supernatant samples in a cohort of adults with acute/early HIV infection, who initiated antiretroviral therapy (ART) during the earliest phase of infection and achieved suppressed levels of HIV RNA in blood plasma (<50 copies/mL) thereafter. We compared BDG with established biomarkers of microbial translocation, immune activation, and cognitive dysfunction (evaluated by global deficit score).We found that higher blood BDG levels were significantly related to higher global deficit scores, reflecting worse neurocognitive performance (Spearman r = 0.47; P = 0.042) among HIV-infected adults with suppressed viral loads who initiated ART early in infection. Two CSF samples presented elevated BDG levels. Interestingly, these 2 samples originated from the 2 subjects with the highest global deficit scores of the cohort.BDG may be a promising independent biomarker associated with neurocognitive functioning in virologically suppressed HIV-infected individuals.

Chemotherapy-Induced Intestinal Mucosal Barrier Damage: a Cause of Falsely Elevated Serum 1,3-Beta-d-Glucan Levels?

Blood citrulline and intestinal fatty acid binding protein were determined as biomarkers for intestinal mucositis. Biomarker levels were correlated with corresponding serum 1,3-beta-D-glucan levels in 56 samples obtained from 33 cases with underlying hematological malignancies receiving induction chemotherapy. No correlation between biomarkers of intestinal mucositis and BDG levels was observed. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.).

1,3-ß-D-glucan concentrations in blood products predict false positive post-transfusion results.

1,3-ß-D-glucan (BDG) is increasingly used to diagnose invasive fungal infections (IFI), although false positive results are a concern. To evaluate the potential interaction of blood products with the BDG assay, human albumin (HA), fresh frozen plasma (FFP), undiluted platelet transfusion (UPT) and packed red blood cells (PRBC) were tested for their BDG content using two different b-D-glucan tests. UPTs tested negative, FFP, PBRC and HA tested positive for BDG. In serial dilution, BDG concentration correlated with blood product concentration. To investigate the clinical impact of blood product transfusions, we measured BDG levels before and after the transfusion in three patients (2 PRBC, 1 HA). In the patients receiving PRBC transfusions, BDG values increased from 13 and 17 pg ml(-1) to 183 and 361 pg ml(-1), the HA transfusion increased the serum level from 42 to 58 pg ml(-1). BDG concentrations measured in blood products can be used to predict false positive BDG results.

Prognostic potential of 1,3-beta-d-glucan levels in bronchoalveolar lavage fluid samples

The objective of this study was to investigate the prognostic potential of 1,3-beta-d-glucan (BDG) testing in bronchoalveolar lavage fluid (BALF) samples. A total of 300 BALF samples from 252 patients were investigated for BDG (Fungitell(®) assay). Prognostic potential of BALF BDG was evaluated by using: i.) Kaplan-Meier analysis, and ii.) multivariable Cox hazard regression analyses. BALF BDG levels were found to be significantly higher in samples with Candida spp. colonization (p<0.001). A total of 61/252 patients (24.2%) died within 90-days of BALF sampling (18.1% of patients with BALF BDG <200pg/mL, 32.4% with BALF BDG ≥200pg/mL). Kaplan-Meier analysis revealed that overall cumulative 90-day mortality was significantly higher in those with BALF BDG levels ≥200pg/mL when compared to those with levels <200pg/mL (log-rank p=0.006, Breslow p=0.005 and Tarone-Ware p=0.005). The multivariable Cox regression analysis showed that BALF BDG levels were a strong predictor of 90-day overall mortality, with a hazard ratio of 1.048 (per 100pg/mL increase of BALF BDG). False positive BALF BDG results in the presence of Candida spp. colonization of the lower respiratory tract may explain the limited diagnostic potential of BALF BDG testing. In contrast, prognostic potential of BALF BDG may be promising.

β-D-Glucan and Candida albicans germ tube antibody in ICU patients with invasive candidiasis.

To assess the performance of (1→3)-β-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) for the diagnosis of invasive candidiasis (IC) in a prospective cohort of 107 unselected, non-neutropenic ICU patients. BDG (cutoff positivity ≥80 pg/mL) and CAGTA (cutoff positivity ≥1/160) assays were performed twice a week. Confounding factors included amoxicillin-clavulanate and piperacillin-tazobactam treatments, recent surgery, Gram-positive bloodstream infection, renal replacement therapy, and enteral nutrition. Patients were classified as neither colonized nor infected (n = 29), Candida spp. colonization (n = 63) (low grade, n = 32; high grade, n = 31), and invasive candidiasis (IC) (n = 15). BDG levels were higher in patients with IC and high-grade colonization than in the remaining groups (p = 0.012), and two consecutive measurements ≥80 pg/mL discriminated IC from the remaining groups (sensitivity 80%, specificity 75.7%). For the discrimination between IC and Candida spp. colonization, the AUC for the maximum value of BDG was 0.667 (95% CI 0.544-0.790) and for the maximum value of CAGTA 0.545 (95% CI 0.395-0.694). Significant changes of BDG and CAGTA kinetics in IC patients treated with antifungals were not observed. In patients neither colonized nor infected or with low-grade Candida spp. colonization, none of the confounding factors was associated with a significant increase in BDG positivity. Two consecutive BDG levels ≥80 pg/mL allowed discrimination among IC and high-grade colonization. Systemic antifungal therapy could not be monitored with biomarker kinetics, and BDG levels were not subject to interference by confounding factors in either colonized or infected patients or with low-grade colonization.

Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis.

Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47) and 65.9% (27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.

β- d -Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

While the assessment of β-D-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (<30%). Receiver operating characteristic analyses suggested an optimal cutoff between 60 and 70 pg/ml for different definitions of the onset of IFD. Our data show that BDG screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness.

(1→3)-β-d-Glucan in Cerebrospinal Fluid as a Biomarker for Candida and Aspergillus Infections of the Central Nervous System in Pediatric Patients.

Fungal infections of the central nervous system (FICNS) are important causes of morbidity and mortality among immunocompromised pediatric patients. Standard diagnostic modalities lack the sensitivity for detecting and therapeutically monitoring these life-threatening diseases. Current molecular methods remain investigational. (1→3)-β-d-glucan (BDG) is a cell wall component found in several fungal pathogens, including Candida and Aspergillus spp. Detecting BDG in cerebrospinal fluid (CSF) may be an important approach for detecting and therapeutically monitoring FICNS. To date, there has been no study that has investigated the effectiveness of CSF BDG as a diagnostic and therapeutic marker of FICNS in children. Serial BDG levels were measured in serum and CSF samples obtained from pediatric patients (aged 0-18 years) with a diagnosis of probable or proven Candida or Aspergillus CNS infection. Nine cases of FICNS were identified in patients aged 1 month to 18 years. Two patients were infected with an Aspergillus species, and 7 patients were infected with a Candida species. All the patients at baseline had detectable BDG in their CSF. Among 7 patients who completed therapy for an FICNS, all elevated CSF BDG levels decreased to <31 pg/mL. At the time of this writing, 1 patient was still receiving therapy and continued to have elevated BDG levels. One patient died from overwhelming disseminated candidiasis. The lengths of therapy for these 9 children ranged from 2 weeks to 28 months. The BDG assay is useful in diagnosing and therapeutically monitoring Candida and Aspergillus CNS infections in pediatric patients.

Adult Living-Donor Liver Transplantation for a Recipient With a High Preoperative 1,3-Beta-d-Glucan Level and Positive Test Result for Aspergillus Antigen

The patient was a 45-year-old man with underlying alcoholic liver cirrhosis. Two years prior, he was repeatedly hospitalized for liver failure symptoms and requested a living-donor liver transplantation (LDLT) because of end-stage cirrhosis. A pretransplantation blood test revealed a high 1,3-beta-d-glucan (BDG) value of 102.0 pg/mL (reference value <20.0 pg/mL) and a high blood Aspergillus antigen (AsAg) value of 1.6 cutoff index (COI; reference value <0.5 COI). Contrast-enhanced thoracoabdominal-pelvic computed tomography (CT) and cranial magnetic resonance imaging revealed no fungal infection. However, latent fungal infection could not be ruled out, hence preoperative antifungal agent treatment was administered. BDG and AsAg levels showed a decreasing trend after treatment initiation. However, normalization did not occur; the BDG and AsAg levels were 25.8 pg/mL and 1.0 COI, respectively. Although the possibility of latent fungal infection was judged low, we prophylactically administered antifungal agents after LDLT. The BDG level consistently increased at 35–39 pg/mL until postoperative day 5 but subsequently normalized. The AsAg level was higher than the limit of detection at 5.0 COI on postoperative day 3 but normalized to 0.2 COI on postoperative day 5 and did not subsequently increase. The postoperative course was uneventful despite bacterial pneumonia and the patient was discharged on postoperative day 35. A histopathologic examination (Grocott methenamine silver staining) and a fungal polymerase chain reaction assay were performed for the resected liver, but the results of both were negative. At 9 postoperative months, the patient was making ambulatory follow-up visits. Currently, the BDG and AsAg values remain normal and clinical progress is favorable. We found no reports of LDLT for a recipient with a high preoperative BDG level and positive test result for AsAg. Thus, we report on such a case with a discussion of the literature on the causes of high preoperative BDG and AsAg values.

Correlation of (1→3)-β-D-glucan with other inflammation markers in chronically HIV infected persons on suppressive antiretroviral therapy.

We evaluated associations between levels of BDG and other biomarkers of inflammation in blood from 41 virologically suppressed persons with chronic HIV-infection. We found a significant correlation between BDG and neopterin levels (r=0.68), and trends to significance for correlations with other inflammation markers (tumor-necrosis-factor-α: r=0.30; interleukin-8: r=0.30; interleukin-6: r=0.28). In conclusion, BDG levels correlated with inflammation markers in a cohort of virologically suppressed individuals with chronic HIV infection. Future studies are needed to evaluate whether BDG may be a marker for morbidity in chronic HIV infection.