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BACKGROUND: Serum 1, 3-β-D-glucan (BDG) assay was recommended for diagnosing fungal infections. AIM: We aimed to assess 1, 3-β-D-glucan in bronchoalveolar lavage (BAL) fluid in invasive pulmonary aspergillosis (IPA). METHODS: Out of 104 patients clinically suspected fungal, 45 were probable, 18 possible, and 41 unlikely according to EORTC/MSG 2008 criteria. Measuring BAL BDG and galactomannan were done. RESULTS: The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for BDG were 44%, 71%, 62%, and 54%; for galactomannan 84%, 83%, 84%, and 83%; and 93%, 66%, 75%, and 90%, respectively, when combining both tests. A significant different performance of GM; p = 0.0008 was detected in patients with malignant disorders when compared to non-malignant; but not for BDG; p = 0.121. CONCLUSION: We can conclude that BAL-BDG is helpful if positive in a clinically suspected IFI case, but if negative cannot rule out fungal infection. Thus, combining results of BAL-GM and BAL-BDG are recommended.

Background: The delayed diagnosis of the presence of Candida in severe intra-abdominal infections exposes patients to an increased risk of mortality. The prevalence of intra-abdominal candidiasis (IAC) varies with the type of intra-abdominal infection, the underlying conditions and the presence of risk factors for Candida infection. This study aims to evaluate the interest of the measure of 1.3-β-D-glucan (BDG) in the peritoneal fluid for the early diagnosis of IAC. Methods and analysis: This is a prospective multicenter (n = 5) non-interventional study, focusing on all critically ill patients with an intra-abdominal infection requiring intra-abdominal surgery. The primary objective is to assess the diagnostic performance of the BDG measured in the peritoneal fluid for the early detection of IAC using the Candida culture as the gold standard. The secondary objective is to report the prevalence of IAC in the selected population. This study aims to enroll 200 patients within 48 months. By estimating the prevalence of IAC in the selected population at 30%, 50 patients with IAC (cases) are expected. These 50 IAC cases will be matched with 50 non-IAC patients (as a control group). The peritoneal BDG will be measured a posteriori in all of these 100 selected patients. This article presents the protocol and the current status of the study. Only the prevalence of IAC is reported as preliminary result.

Background: Invasive candidiasis (IC) occurs in immunocompromised and immunocompetent patients. It represents the 4th bloodstream infection in the ICU. Selection of patient characteristics based on risk factors in the 1,3-β-D-Glucan (BDG) examination provided a learning value in IC screening. The aim of this study was to assess the comparison of risk factors for IC and BDG levels using a cut off value of ≥80 pg/dl. Method: this cross-sectional study was conducted in 40 patients with septic pneumonia in ICU who had the risk factors of IC (multifocal colonization, broad-spectrum antibiotics, long term use of corticosteroids, and lymphocyte status) at Saiful Anwar Malang General Hospital. Results: There were 40 patients with risk factors of IC had positive BDG, but only 1 patient (2,5%) had candidemia and 14 patients (35%) had Candida sp from sputum culture. Comparison of BDG levels between group which used broad-spectrum antibiotics and those that did not wassignificant (P=0.020). Rank Spearman linear regression of the lymphocyte

Background Pneumocystis jirovecii pneumonia (PCP) is a common and potentially fatal opportunistic infection in immunocompromised non-HIV individuals. There are problems with clinical and diagnostic protocols for PCP that lack sensitivity and specificity. We designed a retrospective study to compared several methods that were used in diagnostics of PCP. Patients and methods One hundred and eight immunocompromised individuals with typical clinical picture for PCP and suspicious radiological findings were included in the study. Serum samples were taken to measure the values of (1→3)-β-D-glucan (Fungitell, Associates of Cape Cod, USA). Lower respiratory tract samples were obtained to perform direct immunofluorescence (DIF, MERIFLUOR® Pneumocystis, Meridian, USA) stain and real-time PCR (qPCR). Results Fifty-four (50%) of the 108 patients in our study had (1→3)-β-D-glucan > 500 pg/ml. Patients that had (1→3)-β-D-glucan concentrations < 400 pg/ml in serum, had mean threshold cycles (Ct) 35.43 ± 3.32 versus those that had (1→3)-β-D-glucan concentrations >400 pg/mL and mean Ct of 28.97 ± 5.27 (P < 0.001). If we detected P. jirovecii with DIF and qPCR than PCP was proven. If the concentration of (1→3)-β-D-glucan was higher than 400 pg/ml and Ct of qPCR was below 28.97 ± 5.27 than we have been able be certain that P. jirovecii caused pneumonia (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.62–3.27, P < 0.001). Conclusions Measurement of (1→3)-β-D-glucan or qPCR alone could not be used to diagnose PCP. Diagnostic cut-off value for (1→3)-β-D-glucan > 400pg/ml and qPCR below 30 Ct, allow us to conclude that patient has PCP. If the values of (1→3)-β-D-glucan are < 400 pg/ml and qPCR is above 35 Ct than colonization with P. jirovecii is more possible than PCP.

Aim We assessed the diagnostic accuracy of serum (1 → 3)-β-D-glucan (BDG) for neonatal invasive candidiasis (NIC) using the recommended cut-off usually used in adults for detecting invasive candidiasis and searched for an optimal cut-off for ruling out NIC. Methods We conducted a prospective cross-sectional study at Nantes University medical centre from January 2017 to July 2018. All consecutive newborn infants of less than 28 days of corrected age, with clinically suspected NIC, who underwent BDG assay, were included. Sensitivity and specificity were calculated by using the recommended cut-off of 80 pg/mL. Receiver operating characteristic curve analysis was used to identify an optimal cut-off value. Results We included 55 newborn infants with 61 episodes of suspected NIC. Their median gestational and chronological ages were 28.0 weeks (interquartile range [IQR] 26.4-34.1) and 10.0 days (IQR 6.0-22.0), respectively. Of 61 episodes, seven revealed NIC. Sensitivity and specificity were 85.7% (95% confidence interval [CI] 42.1%-99.6%) and 51.9% (37.8%-65.7%) with the recommended cut-off, respectively. An optimal cut-off of 174 pg/mL offered the same sensitivity but higher specificity 77.8% (64.4%-88.0%). Conclusion The recommended cut-off of 80 pg/mL was probably too low for ruling out NIC. A higher cut-off might have been more appropriate.

Neonatal infectious diseases are a serious threat to the health of newborns. The aim was to establish a new detection method for the simultaneous measurement of (1,3)-β-d-glucan and procalcitonin in serum for the early screening and efficacy testing of neonatal infectious diseases. We established a sandwich dual-label time-resolved fluorescence immunoassay (TRFIA): anti-(1,3)-β-d-glucan/procalcitonin antibodies immobilized on 96-well plates captured (1,3)-β-d-glucan/procalcitonin antigens and then banded together with the detection antibodies labeled with europium(III) (Eu3+ )/samarium(III) (Sm3+ ) chelates. Finally, time-resolved fluorometry was used to measure the fluorescence intensity. The linear correlation coefficient (R2 ) of the (1,3)-β-d-glucan standard curve was 0.9913, and the R2 of the procalcitonin standard curve was 0.9911. The detection sensitivity for (1,3)-β-d-glucan was 0.4 pg/mL (dynamic range: 0.6-90 pg/mL), and the average recovery was 101.55%. The detection sensitivity for procalcitonin was 0.02 ng/mL (dynamic range: 0.05-95 ng/mL), and the average recovery was 104.61%. There was a high R2 between the present TRFIA method and a commercially available assay (R2 = 0.9829 for (1,3)-β-d-glucan and R2 = 0.9704 for procalcitonin). Additionally, the cutoff values for (1,3)-β-d-glucan and procalcitonin were 23.95 pg/mL and 0.055 ng/mL, respectively. The present TRFIA method has high sensitivity, accuracy, and specificity and is an effective method for early screening and efficient testing of neonatal invasive fungal infection.

Hot-press compression molding was attempted to resinify two renewable source-derived linear (1→3)-β-D-glucan polymers, i.e., paramylon or curdlan via the generation of reactive aldehyde groups that...

Serum (1→3)-β-D-glucan (BDG), is an adjunct test in the diagnosis of invasive fungal disease (IFD). Fungitell STAT™, a facile, rapid, single patient option, executable for one or more patient specimens in approximately an hour, has been developed to address a need for rapid in-house testing. This method presents qualitative information concerning serum BDG levels, using an index value that allows the rapid categorization of patients as positive, negative, or indeterminate relative to serum BDG titer. The categorical and analytical performance of Fungitell STAT was evaluated. The categorical agreement between methods was established by testing patient samples which had been previously categorized with Fungitell. Receiver Operating Characteristic curves were used to identify cut-offs using 93 de-identified patient specimens. Subsequently, using these cutoffs, an independent group of 488 patient specimens was analyzed. Positive percent agreement (PPA) with, and without, indeterminate results was 74% and 99%, respectively. Negative percent agreement (NPA) was 91% and 98% with, and without, indeterminate results, respectively. Additionally, commercially available normal off-the-clot sera were spiked with Saccharomyces cerevisiae-derived (1→3)-β-D-glucan to produce analytical samples. Analytical reproducibility using spiked samples was excellent with 94% of the CV (coefficient of variation) values ≤10% among three independent laboratories. Good correlation with the predicate method was demonstrated with correlation coefficients of 0.90 or better with patient samples and 0.99 with spiked samples. The Fungitell STAT index assay provides a rapid and suitable method for serum BDG testing.

(1→3)-β-glucan (BDG) testing as an adjunct in the diagnosis of invasive fungal disease (IFD) has been in use for nearly three decades. While BDG has a very high negative predictive value in this setting, diagnostic false positives may occur, limiting specificity and positive predictive value. Although results may be diagnostically false positive, they are analytically correct, due to the presence of BDG in the circulation. This review surveys the non-IFD causes of elevated circulating BDG. These are in the main, iatrogenic patient contamination through the use of BDG-containing medical devices and parenterally-delivered materials as well as translocation of intestinal luminal BDG due to mucosal barrier injury. Additionally, infection with Nocardia sp. may also contribute to elevated circulating BDG. Knowledge of the factors which may contribute to such non-IFD-related test results can improve the planning and interpretation of BDG assays and permit investigational strategies, such as serial sampling and BDG clearance evaluation, to assess the likelihood of contamination and improve patient care.

Background: Serum (1,3)-β-D-glucan (BG) testing is increasingly being used in the diagnostic armamentarium for invasive fungal diseases. Given its high sensitivity, some studies suggest that a negative BG result contributes to rule out a diagnosis of Pneumocystis pneumonia (PCP). However, recent reports described a suboptimal sensitivity in HIV-negative immunocompromised patients. In this study, we evaluated the performance of BG assay for PCP diagnosis in HIV-negative patients with diverse PCP risk factors. We also assessed the correlation between Pneumocystis jirovecii load in pulmonary samples and serum BG levels.Methods: We retrospectively included HIV-negative patients with microscopically proven PCP and for whom a BG result was available. We also enrolled patients colonized by Pneumocystis as control group. Colonized patients were matched with PCP patients based on their underlying condition that exposed to PCP. Pulmonary fungal loads were determined by an in-house real-time PCR, and BG levels were measured by using the Fungitell® kit (Associates of Cape Cod, Inc.).Results: Thirty-nine patients were included in each of the two groups. Thirty-four of 39 PCP patients and one of 39 colonized patient had a positive BG test, resulting in a sensitivity of 0.87 (95% CI: 0.73–0.94), a specificity of 0.97 (95% CI: 0.87–0.99), a positive predictive value of 0.97 (95% CI: 0.85–0.99), and a negative predictive value of 0.88 (95% CI: 0.75–0.95) for BG assay. Nonetheless, median BG level differed according to the underlying condition. Among the PCP group, the lowest median level of 211 pg/ml was observed in patients with hematological malignancy (HM) and differed significantly from that observed either in solid organ transplants (3,473 pg/ml) or in patients with autoimmune or inflammatory disorder (3,480 pg/ml). Indeed, the sensitivity of BG assay was estimated at 0.64 (95% CI: 0.35–0.85) in HM patients and was lower than the one observed in the whole PCP group. Furthermore, BG level and fungal burden correlated poorly among all PCP patients.Conclusion: BG is not a reliable biomarker for ruling out PCP in HIV-negative patients with HM. Interpretation of a negative BG result should take into account, but not be limited to, the underlying condition predisposing to PCP.

Background: To improve the accuracy in invasive candidiasis diagnostics, a new biomarker panel has been developed and validated on a 165-patient cohort of critically ill adults.Methods: The serum levels of inflammatory biomarkers, C-reactive protein, presepsin (PSEP), procalcitonin (PCT), and of panfungal (1,3)-β-D-glucan (BDG), were correlated with culture-confirmed candidemia or bacteremia in 58 or 107 patients, respectively. The diagnostic effect of the host and pathogen biomarkers was expressed using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).Results: For invasive candidiasis, the best performing BDG exhibited 96.6% sensitivity, 97.2% specificity, 94.9% PPV and 98.1% NPV at a cut-off of 200 pg/mL (P ≤ 0.001). PSEP exhibited 100% sensitivity and 100% NPV at a cut-off of 700 pg/mL. Furthermore, PSEP was more accurate for 28-day mortality prediction (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off 0.5 ng/mL). Finally, PSEP showed a significant serum decrease as early as 14 days after echinocandin therapy initiation (P = 0.0012).Conclusions: At concentrations of BDG > 200 pg/mL and PSEP > 700 pg/mL, the probability of invasive candidiasis in critically ill adults is close to 100% defining a borderline between non-invasive superficial Candida colonization and invasive candidiasis.Trial registration: The study was approved by the University Hospital Ostrava Ethics Committee for Multicenter Clinical Trials (no. 448/2018) and registered in ClinicalTrials.gov (ID: NCT03584594), date of registration June 28,2018.

Background Asymptom of invasive candidiasis (IC) and low positive rate of blood culture lead to delay diagnose of neonatal infection. Serum (1,3)-β-D-glucan (BDG) performs well in adult IC, but its use in neonatal IC is unclear. We evaluated the use of BDG, procalcitonin (PCT), high-sensitive C-reactive protein (hsCRP) or platelet count (PC) in neonatal IC. Methods We collected the data of neonates admitted to our institute. Eighty neonates were enrolled, and divided into IC group, bacterial infection (BI) group and control (CTRL) group. We analyzed the difference of these indicators between groups, and generated Receiver operator characteristic (ROC) curve. The value of BDG in antifungal therapy efficacy assessment was also investigated. Results The BDG level was higher in IC group compared with BI and CTRL group. C. albicans lead to significant increase of BDG compared with C. parapsilosis. IC group had highest hsCRP level and lowest PC. PCT level was similar between groups. ROC showed that BDG or hsCRP performs well in neonatal IC, the optimal cut-off for BDG was 13.69 mg/ml. Combined BDG with hsCRP, PCT and PC increased diagnostic value. Serum BDG level was decreased during antifungal treatment. Conclusion Serum BDG performs well in identification of neonatal IC and in monitoring the antifungal therapy efficacy.

Galactomannan (GM), 1,3-β-D-glucan (BDG) and aspergillus-lateral flow device (LFD) are recognized as diagnostic tools for invasive aspergillosis (IA). The combined performance of these assays, however, is inconsistent in various studies. We undertook a meta-analysis of 13 studies involving 1513 patients to evaluate the utility of GM in combination with BDG or LFD for diagnosing IA. The pooled SEN, SPE, PLR, NLR and diagnostic odds ratio (DOR) were calculated and constructed to summarize the overall combined performance. Combining both positive results of GM and BDG assays leaded to the pooled SEN 0.49 (95%CI 0.27-0.72), SPE 0.98 (95%CI 0.94-1.00), PLR 31.68 (95%CI 5.36-187.37), NLR 0.52 (95%CI 0.32-0.84) and DOR 61.23 (95%CI 6.96-538.90). Comparing with GM and BDG assays, both positive results of GM and LFD leaded to high SEN, similar SPE, low PLR and NLR. At least one positive result of GM or LFD conferred great SEN 0.93 and low NLR 0.08. Both positive results of GM and BDG or LFD assay were in favor of confirming the existence of IA. And both negative results of GM and LFD were beneficial to rule out IA. Further studies with sufficient sample size should focus on the diagnostic performance and cost-effectiveness of these combined tests in clinical setting.

1,3-β-D-glucan (BG), a cell-wall component of most fungi including Pneumocystis (PC), is recommended by international guidelines for screening for pneumocystis pneumonia (PCP) in hematologic patients. We retrospectively validated the BG test in our tertiary university hospital. Forty-five patients (median age 53 years, 33% female) tested for PC by polymerase chain reaction (PCR) and/or immunoflourescence (IF)-microscopy with a stored blood sample within ±5 days of the PC test were tested by the Fungitell (cutoff 80 pg/ml). Cases had symptoms and radiology compatible with PCP and positive IF-microscopy (proven PCP, n = 8) or positive PCR (probable PCP, n = 10). Controls had no compatible symptoms/radiology and negative tests for PC on conventional testing (no PCP, n = 24), or positive PCR/IF-microscopy (colonized, n = 3). Median BG-levels were 1108 pg/ml (proven PCP), 612 pg/ml (probable PCP), 29 pg/ml (colonized), and 48 pg/ml (controls, P < 0.001). Compared to the PCP case/control classification, the BG test showed sensitivities of 83–89% and specificities of 64–74%, positive likelihood ratio (LR) of 3.2 and negative LR of 0.23 at recommended cutoff and moderate agreement between tests. Optimal cutoff was ≥73 pg/ml. In PCR-positive cases, the agreement between the BG test and IF-microscopy was 78–89% with fair/moderate agreement. Elevated BG levels were seen in controls with probable invasive fungal infections (n = 4), hemodialysis, bacterial infections and/or betalactams. To conclude, 11% of patients with PCP would be missed if the BG test had been used for diagnosing PCP. Specificity was moderate. Among PCR-positive patients, the BG test identified more cases than IF-microscopy. BG testing is potentially helpful but sensitivity is insufficient to exclude PCP.

Detection of 1,3-β-d-glucan (BDG) in serum has been evaluated for its inclusion as a mycological criterion of invasive fungal infections (IFI) according to EORTC and Mycoses Study Group (MSG) definitions. BDG testing may be useful for the diagnosis of both invasive aspergillosis and invasive candidiasis, when interpreted in conjunction with other clinical/radiological signs and microbiological markers of IFI. However, its performance and utility vary according to patient population (hematologic cancer patients, solid-organ transplant recipients, intensive care unit patients) and pretest likelihood of IFI. The objectives of this article are to provide a systematic review of the performance of BDG testing and to assess recommendations for its use and interpretation in different clinical settings.

In this retrospective study, (1–>3)-β-d-glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common, attributing B-glucan positivity to PCP without further testing risks misdiagnosis.

The implementation of 1,3 &beta, d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre&ndash, post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%, p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29, p &lt, 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%, p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 &euro, /patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.

Data on biomarker-assisted diagnosis of invasive aspergillosis (IA) in pediatric patients is scarce. Therefore, we conducted a cohort study over two years including 404 serum specimens of 26 pediatric patients after allogeneic hematopoietic stem cell transplantation (alloSCT). Sera were tested prospectively twice weekly for Aspergillus-specific DNA, galactomannan (GM), and retrospectively for (1→3)-β-D-glucan (BDG). Three probable IA and two possible invasive fungal disease (IFD) cases were identified using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSGERC) 2019 consensus definitions. Sensitivity and specificity for diagnosis of probable IA and possible IFD was 80% (95% confidential interval (CI): 28–99%) and 55% (95% CI: 32–77%) for BDG, 40% (95% CI: 5–85%) and 100% (95% CI: 83–100%) for GM, and 60% (95% CI: 15–95%) and 95% (95% CI: 75–100%) for Aspergillus-specific real-time PCR. However, sensitivities have to be interpreted with great caution due to the limited number of IA cases. Interestingly, the low specificity of BDG was largely caused by false-positive BDG results that clustered around the date of alloSCT. The following strategies were able to increase BDG specificity: two consecutive positive BDG tests for diagnosis (specificity 80% (95% CI: 56–94%)), using an optimized cutoff value of 306 pg/mL (specificity 90% (95% CI: 68–99%)) and testing BDG only after the acute posttransplant phase. In summary, BDG can help to diagnose IA in pediatric alloSCT recipients. However, due to the poor specificity either an increased cutoff value should be utilized or BDG results should be confirmed by an alternative Aspergillus assay.

Pneumocystis jirovecii pneumonia is a difficult invasive infection to diagnose. Apart from microscopy of respiratory specimens, two diagnostic tests are increasingly used including real-time quantitative PCR (qPCR) of respiratory specimens, mainly in bronchoalveolar lavage fluids (BAL), and serum &beta, 1,3-d-glucan (BDG). It is still unclear how these two biomarkers can be used and interpreted in various patient populations. Here we analyzed retrospectively and multicentrically the correlation between BAL qPCR and serum BDG in various patient population, including mainly non-HIV patients. It appeared that a good correlation can be obtained in HIV patients and solid organ transplant recipients but no correlation can be observed in patients with hematologic malignancies, solid cancer, and systemic diseases. This observation reinforces recent data suggesting that BDG is not the best marker of PCP in non-HIV patients, with potential false positives due to other IFI or bacterial infections and false-negatives due to low fungal load and low BDG release.

Chronic disseminated candidiasis (CDC) is a type of invasive candidiasis. CDC commonly appears in the neutrophil recovery phase after chemotherapy in patients with hematologic malignancies, and immune reconstitution inflammatory syndrome (IRIS) is thought to play a major role in CDC development. This report describes the case of a 33-year-old man with CDC as a complication of acute myeloid leukemia. We describe the clinical course, body temperature, therapy, and (1,3)-β-D-glucan (BDG) levels over the course of 22 months. He was initially treated with antifungals, but corticosteroids were added because of a persistently elevated body temperature, which we attributed to IRIS. After starting corticosteroids, his clinical condition improved, but his BDG levels became markedly elevated. We hypothesize that the suppression of the excessive immune response by corticosteroids lead to granuloma collapse, fungal release, and hematogenous dissemination, resulting in elevated BDG levels. The patient's condition gradually improved over the course of follow-up.

We evaluated the performance of the (1,3)-β-d-glucan (BDG) assay on bronchoalveolar lavage fluid (BALF) as a possible aid to the diagnosis of Pneumocystis jirovecii pneumonia. BALF samples from 18 patients with well-characterized proven, probable, and possible Pneumocystis pneumonia and 18 well-matched controls were tested. We found that the best test performance was observed with a cut-off value of 128 pg/mL; receiver operating characteristic/area under the curve (ROC/AUC) was 0.70 (95% CI 0.52–0.87). Sensitivity and specificity were 78% and 56%, respectively; positive predictive value was 64%, and negative predictive value was 71%. The low specificity that we noted limits the utility of BALF BDG as a diagnostic tool for Pneumocystis pneumonia.

International audience; Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-β-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P

Background Candidemia is a major cause of bloodstream infection in tertiary hospitals worldwide and fungal biomarkers may provide early diagnosis. Objectives To evaluate the performance of (1-3)-β-D-glucan (BDG) in the diagnosis of candidemia, and its ability to predict therapeutic failure. Patients and methods This was a prospective, multi-center study conducted in 3 Brazilian hospitals. Clinical outcome was evaluated along 2 weeks of treatment, and therapeutic failure was defined as the occurrence of persistent candidemia, Candida deep-seated infection or death. Baseline BDG detection was performed with the Fungitell® assay (Associates of Cape Cod, Falmouth - USA). Results We enrolled a total of 71 patients with candidemia and a control group with 110 healthy volunteers. The sensitivity and specificity of BDG for diagnosing candidemia were: 71.8 % (95 % confidence interval [95 % CI] 59.7 % - 81.5 %) and 98.2 % (95 % CI 92.9 % - 99.7 %), respectively. The only predictor of therapeutic failure was a higher BDG value at diagnosis of candidemia; a value >226 pg/mL predicted failure with sensitivity and specificity of 75 % and 78 %, respectively. Conclusions A high baseline serum BDG value was associated with therapeutic failure.

Background 1,3 β-D-Glucan is an important marker for diagnosis of invasive fungal infection (IFI).Its value in comparison to blood culture is not yet established in neonates. Aim primary aim is to study the value of 1,3 β-D-Glucan in comparison with culture on Sabouraud dextrose agar in diagnosis of IFI, Secondary aim is to study the prevalence of IFI in preterm neonates. Subjects and methods a prospective observational study carried on 75 non-exclusively breast fed preterm neonates ≤34 weeks gestational age. Tollner and Rodwell sepsis scores, SNAPII and blood culture were done to all neonates initially and on day 10&17 of life. 1,3 β-D-Glucan was done for all neonates on day 10 of life. Results fungal growth was found in 9.3% of included preterm neonates.1,3β-D-Glucan was higher in culture proven fungal sepsis compared to culture proven bacterial sepsis and culture negative preterm neonates (83.28±26.22 pg\ µl, 51.42±16.71 pg\ µl, 43.07±12.87 pg\ µl respectively). 1,3 β-D-Glucan was related to Tollner (r = 0.286,p=0.013), Rodwell (r = 0.317,p=0.006) sepsis scores and to SNAPII score (r = 0.331,p=0.04). Its cut off point for diagnosis of IFI is 79pg\µl with sensitivity of 71% and specificity of 98%. Conclusion 1,3β-D-Glucan is an easy, rapid and specific marker for diagnosis of IFI in neonates. Further studies are needed to evaluate it as a therapeutic monitoring for IFI.

Background: An evidence gap exists in anti-fungal diagnostic practice following abdominal surgery, especially when compared to haem-oncology counterparts. In light of the recent Anti-fungal Stewardship CQUIN, our study addresses the utility of serum (1,3)-β-D-Glucan (BDG) testing post-gastrointestinal surgery. Method: We identified positive BDG results (>/=80pg/mL) on ITU and surgical wards in 3 major institutions in the Bristol area. Those with a ‘history of abdominal surgery

Objectives: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available β-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. Methods: BDG results by Wako β-glucan assay (lower limit of detection [LLOD]=2.16pg/mL, positivity≥11pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N=42), intensive care units (ICUs; N=80), or other wards (N=48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. Results: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values7.7pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

Summary People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualise and culture fungi before initiating treatment. Such techniques are less practical in resource‐limited settings due to their cost and requirement of relatively invasive procedures. Hence, identification of surrogate markers for the early diagnosis and therapeutic monitoring of IFIs is required. Recent studies have shown that (1→3)‐β‐d‐glucan (BDG), a major fungal cell wall antigen, represents a promising soluble marker for the presumptive diagnosis and therapeutic monitoring of IFIs in HIV‐infected patients. Herein, we review findings on the merits of BDG assays in the diagnosis of IFIs and monitoring of antifungal therapies for PLHIV. Conversely to other types of immunocompromised patients, HIV infection is associated with gut damage and subsequent bacterial and fungal translocation leading to elevated BDG plasma levels.

We analyze the prognostic potential of (1 → 3)-β-D-glucan (BG) levels in predicting clinical outcomes in patients with invasive fungal infections, on a population undergoing 253 episodes (177 with positive and 76 with negative outcome). Using linear regression analysis, we assessed the prognostic potential of kinetically evaluated BG levels and we found an overall sensitivity and specificity of 68 and 82%, respectively. Moreover, using an interpretative algorithm based on two distinct cutoff values, we were able to predict the outcome in 84% of the studied population with a diagnostic accuracy of 82%.

The aim of this study was to evaluate the ability of heat-killed baker's yeast (HKBY), the cell wall of baker's yeast (CWBY), and cell wall (1→3)-β-d-glucan of baker's yeast (BGBY) to bind aflatoxin B1 (AFB1) in phosphate-buffered saline (PBS) spiked with 0.5 μg/mL AFB1. Baker's yeast ( Saccharomyces cerevisiae) was heat killed by autoclaving at 121°C for 10 min. The cell wall was physically extracted, and (1→3)-β-d-glucan was extracted by a modified method. The concentration of AFB1 was determined by high-performance liquid chromatography after exposure to binders for three contact times, 30 min, 5 h, and 24 h, at room temperature. AFB1 binding by HKBY, CWBY, and BGBY was 6.30 to 46.34%. The lowest binding capacity was found for HKBY with a contact time of 30 min, and the highest binding capacity was found for BGBY with a contact time of 24 h. Among binders, CWBY had the highest binder-AFB1 complex stability during washing with PBS, and the lowest stability was found for HKBY complexes. Results of this study indicated that BGBY was the most effective binder, and more exposure to BGBY removes more AFB1 from PBS.

(1→3)-β-D-glucan is a major component of the fungal cell wall. It is commonly used to evaluate human exposure to fungi. A personal sampling system was developed to size-selectively evaluate the workplace protection factors (WPFs) of N95 filtering facepiece respirators (FFRs) and surgical masks (SMs) against fungi. This field study was performed with human subjects wearing an N95 FFR or a SM during farming activities. The geometric means of the WPFs of N95 FFRs and SMs were 156.2 and 12.2 for the total culturable fungi, 55.4 and 9.0 for the total fungi, and 10.5 and 11.1 for (1→3)-β-D-glucan. The WPFs for N95 FFRs against fungal contaminants were mostly greater than those for SMs; however, about 4.8%–35.0% of WPFs in the spore size range > 1.8 µm were still below 10 (the assigned protection factor designated for N95 FFRs by the US Occupational Safety and Health Administration). The WPFs of N95 FFRs and SMs against culturable fungi and (1→3)-β-D-glucan increased with the particle size. The total (1→3)-β-D-glucan significantly correlated with the total fungi (r = 0.588, p < 0.001) and total culturable fungi (r = 0.463, p = 0.002), which suggests that (1→3)-β-D-glucan can be used as an indicator to assess respiratory protection against airborne fungi on agricultural farms.

We investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in a lupus model with Fc gamma receptor IIb-deficient (FcGRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. Spontaneous gut leakage, determined by (i) the presence of FITC-dextran, (ii) elevated serum endotoxin, and (iii) elevated serum (1→3)-β-D-glucan (BG), was demonstrated in symptomatic lupus but not in the asymptomatic group. In parallel, spontaneous gut leakage, detected by elevated serum BG without fungal infection, was demonstrated in patients with active lupus nephritis. Gut leakage induced by dextran sulfate solution (DSS) or endotoxin administration together with BG or endotoxin alone, but not BG alone, enhanced the severity of cecal ligation and puncture (CLP) sepsis more prominently in 8-week-old FcGRIIb-/- mice. Additionally, the bone marrow-derived macrophages of FcGRIIb-/- mice produced higher cytokine levels when coexposed to endotoxin and BG, when compared to wild-type mice. In summary, spontaneous gut leakage was demonstrated in symptomatic FcGRIIb-/- mice and the induction of gut permeability worsened sepsis severity. Gut translocation of endotoxin and BG had a minor effect on wild-type mice, but the synergistic effect of BG and endotoxin was prominent in FcGRIIb-/- mice. The data suggest that therapeutic strategies addressing gut leakage may be of interest in sepsis conditions in patients with lupus.

Nanocellulose-based biomaterials for biomedical and pharmaceutical applications have been extensively explored. However, studies on different levels of impurities in the nanocellulose and their potential risks are lacking. This article is the most comprehensive to date survey of the importance and characterization of possible leachables and extractables in nanocellulose for biomedical use. In particular, the (1,3)-β- d -glucan interference in endotoxin detection in algal nanocellulose was addressed. Potential lipophilic and hydrophilic leachables, toxic heavy metals, and microbial contaminants are also monitored. As a model system, nanocellulose from Cladophora sp. algae is investigated. The leachable (1,3)-β- d -glucan and endotoxin, which possess strong immunogenic potential, from the cellulose were minimized to clinically insignificant levels of 4.7 μg/g and 2.5 EU/g, respectively. The levels of various impurities in the Cladophora cellulose are acceptable for future biomedical applications. The presented approach could be considered as a guideline for other types of nanocellulose.

In this study, we evaluated the levels of airborne biological agents, such as bacteria, fungi, endotoxin, and (1→3)-β-d-glucan in university fish toxicity laboratory every month for one year and assessed the associated environmental factors. A single-stage viable cascade impactor connected with a pump was used for culturable bacteria and fungi. An analysis of airborne endotoxin and (1→3)-β-d-glucan was performed using kinetic Limulus amebocyte lysate assays. Levels of culturable bacteria and fungi were the highest in summer, whereas levels of endotoxin and (1→3)-β-d-glucan were the highest in winter and spring, respectively. Human activity was correlated with culturable bacteria and fungi, and culturable fungi were also associated with culturable bacteria. Although additional studies based on advanced analyzing technology are required, simultaneous sampling with biomarkers of bacteria is required to further elucidate the characteristics of biological agents.

Invasive fungal disease (IFD) can be caused by a range of pathogens. Conventional diagnosis has the capacity to detect most causes of IFD, but poor performance limits impact. The introduction of non-culture diagnostics, including the detection of (1-3)-β-D-Glucan (BDG), has shown promising performance for the detection of IFD in variety of clinical settings. Recently, the Dynamiker® Fungus (1-3)-β-D-Glucan assay (D-BDG) was released as an IFD diagnostic test. This article describes an evaluation of the D-BDG assay for the diagnosis of invasive aspergillosis (IA), invasive candidiasis (IC) and Pneumocystis pneumonia (PCP) across several high-risk patient cohorts and provides comparative data with the Associates of Cape Cod Fungitell® and BioRad Platelia™ Aspergillus Ag (GM) assays. There were 163 serum samples from 121 patients tested, from 21 probable IA cases, 28 proven IC cases, six probable PCP cases, one probable IFD case, 14 possible IFD cases and 64 control patients. For proven/probable IFD the mean BDG concentration was 209pg/ml, significantly greater than the control population (73pg/ml; P

Serum (1→3) beta-D-glucan (BG) measurement is a useful test for systemic mycoses, and often used. On the other hand, various factors, including administration of intravenous immunoglobulins (IVIG) may cause false-positives. In the present study, we measured BG concentration of seven IVIG preparations with three lots respectively. BG levels varied with individual IVIG preparations (3.0 -300 pg/mL), and contamination from manufacturing processes was suspected. With serum BG concentration of clinical specimens obtained in Niigata University MedicalDental Hospital, the difference between before and after administration of IVIG were calculated. The false-positive rate of BG due to IVIG administration was 9.8 %, and the positive predective value was reduced to 37.5%. Above all, administration of IVIG can complicate the BG test's interpretation, and caution is required.

In 1985, a (1→3)-β-D-glucan assay based on the discovery of a (1→3)-β-D-glucan-sensitive coagulation factor in the horseshoe crab amebocytes was developed in Japan, as a test aid in the diagnosis of invasive fungal infections. After many clinical trials, it has now been incorporated in practice guidelines both in Japan and abroad for the diagnosis and management of invasive fungal infection, and is now available worldwide. In Japan, however, two commercial kits that differ widely in sensitivity to (1→3)-β-D-glucan are used; namely, the colorimetric and the turbidimetric assays. Thus, attention must be paid when comparing measurement values between the two tests. In most cases, one pg/ml of the latter corresponds to about 7 pg/ml of the former. This raises the cutoff value of the turbidimetric assay far higher than that of the colorimetric assay, raising concern about missing many true cases of invasive fungal infections. The detection limit of the turbidimetric method is equivalent to as high as 60 pg/ml if converted to the colorimetric measurement. Thus, early diagnosis will be difficult to make based on detection of a rise in the β-D-glucan level in the lower range of concentration. The kits used overseas also differ in sensitivity; thus, global standardization or harmonization will be required to establish inter-assay data comparability and to enhance the usefulness of the tests. In the future, genetic engineering may provide an alternative source of the coagulation pathway enzymes other than the horseshoe crabs, in accordance with the global trends in animal protection, and bring about new opportunities for standardization.

Gastrointestinal (GI) leakage is believed to exacerbate sepsis and new, validated markers of GI barrier performance might benefit clinical decision-making. Serum (1→3)-β-D-glucan (BG) was evaluated as a potential GI leakage marker. Serum BG was tested in several mouse models of GI leakage, including dextran sulfate solution (DSS) administration, endotoxin (LPS) injection, and cecal ligation and puncture sepsis (CLP). Serum BG titer was also evaluated in patients with sepsis and septic shock, for comparison.With 0.75% DSS administration, BG increased only after oral administration of heat-killed C. albicans, but increased spontaneously with 1.5% DSS. In the LPS and CLP models, BG increased as early as 1 h and at 12 h after LPS administration and surgery, respectively. GI leakage was confirmed by orthogonal validation methods including FITC-dextran oral administration in the DSS, LPS, and CLP models and, in the DSS model, with urine sucralose after oral administration and serum endotoxemia. IL-6 increased in parallel with serum BG. Serum BG or IL-6, at 18 h, anticipated sepsis mortality in the CLP model.Analysis of serum BG from patients with febrile neutropenic sepsis (N = 49) and febrile non-neutropenic sepsis (N = 39) demonstrated BG elevation. Patients with bacterial septic shock had serum BG titers similar to levels observed in invasive fungal disease, regardless of febrile neutropenia. Serum BG was lower in less severe cases of bacterial sepsis. Elevated serum IL-6 was associated with GI leakage and elevated serum BG.Serum BG may have potential as a sepsis/septic shock biomarker and further study in this context is warranted.

Background Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP. Method We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves. Results Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87–94%) and 79% (95%CI 72–84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91–96%) versus 86% (95%CI 78–91%) (p 0.02), with comparable specificity (83%, 95%CI 69–92% versus 83%, 95%CI 72–90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV). Conclusions Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.

Background We report an invasive pulmonary aspergillosis (IPA) with negative (1,3)-β-D-glucan and dynamically elevated white blood cells combined with procalcitonin proven by bronchoalveolar lavage fluid (BALF) culture. Methods Appropriate laboratory tests are carried out. Chest CTs were performed to assess the lungs. The cause of infection was determined using BALF culture. Results Serum (1,3)-β-D-glucan was negative, white blood cells and procalcitonin were significantly higher than normal. The bronchoscopy revealed obvious necrotic detritus and pseudo membrane in the trachea, left and right main bronchi, and branches. BALF culture revealed the presence of Aspergillus. Conclusions Negative (1,3)-β-D-glucan is not safe to rule out invasive pulmonary aspergillosis. BALF culture is critical for IPA diagnosis.

Here, we report comparable results of the Wako β-Glucan test (GT; FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan), recently launched in Europe for testing the invasive fungal disease (IFD) biomarker 1,3-β-D-glucan (BDG) (1–3), in matched serum and plasma samples from patients with IFD.…

Background Paracoccidioidomycosis (PCM) is highly prevalent in Latin America, but no commercial system is available for diagnosing this endemic mycosis. Objectives To check the performance of (1 → 3)-β-D-glucan assay (BDG) for diagnosing PCM in 29 patients with proven fungal disease and compared with double immunodiffusion assay for detecting anti-Paracoccidioides antibodies. Patients and methods We selected 52 serum samples sequentially obtained from 29 patients with active PCM (12 chronic and 17 acute form). Samples were collected at baseline, and for 16 patients, additional serum levels were obtained after 3 and 6 months of antifungal treatment. Detection of BDG in serum was performed by using the Fungitell® assay. For the double immunodiffusion assay, Paracoccidioides exoantigen was used in latex agglutination tests to detect serum anti-Paracoccidioides antibodies. Results Despite exhibiting good sensitivity in the diagnosis of patients with PCM, we failed to demonstrate any correlation between the postdiagnosis kinetic profile of BDG serum levels and clinical response to antifungal therapy. This finding may be related to the maintenance of quiescent foci of fungal infection in several organs and tissues, a phenomenon that has been previously reported by other authors and helps to understand why so many relapses are documented in patients treated for short periods of time. Finally, we did not find any correlation between BDG quantification and specific anti-P brasiliensis antibodies serum titres in patients with PCM. Conclusions In conclusion, BDG is detected in serum samples of most patients with PCM but is probably not useful for predicting clinical response to antifungal therapy.