epiglucan and Fungemia

To assess the diagnostic accuracy of 1,3-β-D-glucan (BDG) assay for diagnosing invasive fungal infections (IFI), we searched the Medline and Embase databases, and studies reporting the performance of BDG assays for the diagnosis of IFI were identified. Our analysis was mainly focused on the cutoff level. Meta-analysis was performed using conventional meta-analytical pooling and bivariate analysis. Our meta-analysis covered 28 individual studies, in which 896 out of 4214 patients were identified as IFI positive. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic (AUC-SROC) curve were 0.78 [95% confidence interval (CI), 0.75-0.81], 0.81 (95% CI, 0.80-0.83), 21.88 (95% CI, 12.62-37.93), and 0.8855, respectively. Subgroup analyses indicated that in cohort studies, the cutoff value of BDG at 80 pg/mL had the best diagnostic accuracy, whereas in case-control studies the cutoff value of 20 pg/mL had the best diagnostic accuracy; moreover, the AUC-SROC in cohort studies was lower than that in case-control studies. The cutoff value of 60 pg/mL has the best diagnostic accuracy with the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria as a reference standard. The 60 pg/mL cutoff value has the best diagnostic accuracy with the Fungitell assay compared to the BDG detection assay. The cutoff value of 20 pg/mL has the best diagnostic accuracy with the Fungitec G-test assay, and the cutoff value of 11 pg/mL has the best diagnostic accuracy with the Wako assay. Serum BDG detection is highly accurate for diagnosing IFIs. As such, 60 pg/mL of BDG level can be used as the best cutoff value to distinguish patients with IFIs from patients without IFI (mainly due to Candida and Aspergillus).

Topics: beta-Glucans; Fungemia; Humans; Proteoglycans; ROC Curve; Sensitivity and Specificity

Topics: beta-Glucans; Biomarkers; DNA, Fungal; Fungemia; Galactose; Humans; Immunocompromised Host; Mannans; Neoplasms; Sepsis

The laboratory diagnosis of invasive candidiasis is based on the demonstration of tissue invasion by Candida, the culture of the fungus in specimens from sterile body sites and the detection of a number of biomarkers including some antibodies, mannan, beta-1,3-D-glucan and Candida DNA.. Description and evaluation of results obtained in published studies on the usefulness of biomarkers in the diagnosis of invasive candidiasis.. A search was performed in the PubMed/Medline database from the National Library of Medicine since January 2000 on the usefulness of biomarkers in the diagnosis of invasive candidiasis. Key words used included candidiasis, Candida, diagnosis, biomarkers, antigen, antibodies, DNA, mannan, and beta-1,3-D-glucan.. Forty one papers dealing with the use of biomarkers in the diagnosis of invasive candidiasis were selected and evaluated, paying special attention to the sensitivity and specificity obtained with the tests used.. Important advances are being reached in the use of biomarkers for the diagnosis of invasive candidiasis, and some of them are being used to start a preemptive therapy strategy.

Topics: Animals; Antibodies, Fungal; beta-Glucans; Biomarkers; Body Fluids; Candida; Candidiasis; DNA, Fungal; False Negative Reactions; False Positive Reactions; Fungemia; Humans; Mannans; Mice; Proteoglycans; Reagent Kits, Diagnostic; Sensitivity and Specificity

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years.

Topics: Anidulafungin; Antifungal Agents; Aspergillosis; beta-Glucans; Candidiasis; Clinical Trials as Topic; Critical Care; Diabetes Complications; Disease Susceptibility; Echinocandins; Fungemia; Galactose; Hematologic Diseases; Humans; Immunocompromised Host; Mannans; Meta-Analysis as Topic; Mycoses; Neoplasms; Opportunistic Infections

The usefulness of surrogate markers in the diagnosis of invasive fungal infections caused by Aspergillus and other emerging mycelial fungi is based on the ability of surrogate markers to detect the infection caused by different species of mycelial fungi. Conventional microbiological methods for diagnosis of fungal disease are slow and insensitive. Antigen based assays or measurement of (1-3)-beta-D-glucan in blood have been developed and validated in clinical laboratories. We review these diagnostic contemporary tools, their clinical application and impact.

Topics: Antibodies, Fungal; Antigens, Fungal; Aspergillosis; beta-Glucans; Biomarkers; Clinical Trials as Topic; Communicable Diseases, Emerging; DNA, Fungal; Early Diagnosis; Fungemia; Galactose; Humans; Immunologic Techniques; Mannans; Predictive Value of Tests; Proteoglycans; Risk Factors; Zygomycosis

In the last years, the main advances in the serological diagnosis of mycoses caused by yeasts have occurred in the area of antibody and (1-3)-beta-D-glucan detection. Commercialization of the Candida albicans IFA IgG test and detection of antibodies against recombinant antigens Hwp1 and enolase are the most important contributions to the first area. Detection of (1-3)-beta-D-glucan confirms its usefulness as a good marker for the diagnosis of invasive candidiasis. The most recent studies suggest that combination of two tests to detect antígen, antibodies, (1-3)-beta-D-glucan and DNA will be needed to optimize the diagnosis of systemic yeast infections.

Topics: Antibodies, Fungal; Antigens, Fungal; beta-Glucans; Biomarkers; Candida albicans; Candidiasis; DNA, Fungal; Early Diagnosis; Fungemia; Humans; Mycoses; Proteoglycans; Yeasts

Topics: Anidulafungin; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Caspofungin; Cross Infection; Echinocandins; Fungemia; Humans; Infusions, Intravenous; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Peptides, Cyclic; Practice Guidelines as Topic

The dramatic increase in nosocomial invasive mycoses over the past two decades has led to increased interest in the area of antifungal development. Unfortunately, the infusion of new diagnostic technology into the clinical mycology laboratory has lagged behind. Although newer, automated, continuous-monitoring blood culture systems are as sensitive as the older, manual "gold standard" system, the recovery of fungi from blood, as well as other clinical specimens, remains an insensitive marker for invasive fungal infection. Antigen assays for the rapid diagnosis of invasive fungal infections are in development, and galactomannan and glucan are two such promising antigens. Glucan may be present in the blood of patients with infection secondary to a wide variety of fungal pathogens, including Candida, Aspergillus, Fusarium, Saccharomyces, Trichosporon and Acremonium species. Early data suggest galactomannan may be present in the blood in detectable levels very early in the course of invasive aspergillosis. The galactomannan assay currently undergoing evaluations may actually be positive prior to the clinical suspicion for infection and may be useful in monitoring therapeutic response as well; however, the etiology of false-positive results following cytotoxic chemotherapy still has to be elucidated. PCR assays are also being developed in the research laboratory, however, the PCR assays will require a significant amount of adaptation and validation before they are ready for clinical care. Well-planned studies to evaluate the performance characteristics as well as appropriate clinical and cost-effective application of these new tests are needed.

Topics: Antigens, Fungal; Aspergillosis; beta-Glucans; Biotechnology; Candidiasis; Centrifugation; Culture Media; Enzyme-Linked Immunosorbent Assay; Fungemia; Glucans; Humans; Immunocompromised Host; Mannans; Medical Laboratory Science; Membrane Glycoproteins; Mycoses; Polymerase Chain Reaction

The usefulness to diagnose and monitor invasive candidiasis (IC) using beta-glucan (BG) and antibodies against Candida albicans germ tubes (CAGT) was evaluated in a twice-weekly screening of 35 episodes in neutropenic adults at high risk. Three proven IC and three probable IC were assessed. Diagnostic levels of both markers were detected in 100% of proven IC and in 66% of probable IC. Sensitivity, specificity, positive and negative predictive values of BG and anti-CAGT antibodies detection were 83.3%, 89.6%, 62.5% and 96.3%, and 83.3%, 86.2%, 55.5%, 96.1%, respectively. False positive reactions occurred at a rate of 10.3% and 13.8% for the detection of BG and anti-CAGT antibodies, respectively. However, the patients with false positive results were different by each test. Both tests anticipated the clinical and radiological diagnosis, and the initiation of antifungal therapy in most patients. Combination of both tests improved specificity and positive predictive value to 100%.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anemia, Aplastic; Antibodies, Fungal; Antibody Specificity; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida albicans; Candidiasis; False Positive Reactions; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Hepatitis; Humans; Liposomes; Male; Middle Aged; Neutropenia; Patient Isolation; Predictive Value of Tests; Sensitivity and Specificity

(1-->3)-beta-D-Glucan is one of the major structural components of fungi, and it seems that it can be detected by the fractionated (1-->3)-beta-D-glucan-sensitive component from a Limulus lysate, factor G. We evaluated the concentration of (1-->3)-beta-D-glucan by using factor G and other fungal antigens in 24 patients with clinical evidence of mycosis and 36 healthy subjects. The mean concentration of (1-->3)-beta-D-glucan in the plasma of the healthy subjects was found to be 2.7 +/- 1.9 pg/ml (range, < 6.9 pg/ml), and it was found to be substantially higher in all 11 patients with candidemia (mean, 2,207.4 pg/ml; range, 325.4 to 8,449.0 pg/ml). Eight of those 11 patients with candidemia (73%) were positive for the Cand-Tec heat-labile candida antigen and only 3 patients (27%) were positive for mannan antigen. Three patients with invasive pulmonary aspergillosis were positive for galactomannan and had, in addition, high concentrations of (1-->3)-beta-D-glucan (mean, 323.3 pg/ml; range, 27.0 to 894.0 pg/ml). All 10 patients with cryptococcosis (including 2 patients with probable cryptococcosis) were positive for cryptococcal antigen by the Eiken latex test; however, (1-->3)-beta-D-glucan levels were not elevated in these patients (mean, 7.0 pg/ml; range, < 16.5 pg/ml). Our results indicated that (1-->3)-beta-D-glucan levels are elevated in patients with candidiasis and aspergillosis but not in those with cryptococcosis.

Topics: Adult; Antigens, Fungal; Aspergillosis; beta-Glucans; Candidiasis; Cryptococcosis; Female; Fungemia; Galactose; Glucans; Humans; Limulus Test; Male; Mannans; Middle Aged; Serologic Tests

This study was conducted to identify the mycological pattern, and to calculate the diagnostic accuracy of serum (1,3)-b-D-glucan for screening fungal sepsis in 351 high-risk neonates. Candida tropicalis was the most common isolate (n=16, 38.1%). At optimum cut-off (47.2 pg/mL), sensitivity and specificity of serum (1,3)-b-D-glucan were 92.9% and 69.9%, respectively.

Topics: beta-Glucans; Fungemia; Glucans; Humans; Infant, Newborn; Proteoglycans; Sensitivity and Specificity

We investigated the clinical performance of (1 → 3)-β-D-glucan (BG), as an early marker of invasive fungal infections (IFI), in different clinical settings.. BG serum levels were assessed by Fungitell (Associates of Cape Cod, Inc), in parallel with galactomannan (GM) when requested by clinicians. By a prospective monocentric study, 270 episodes at risk or with suspect of IFI were enrolled, namely 58 proven-probable invasive aspergillosis (IA), 27 proven invasive candidiasis (IC), 11 possible IC, 16 P.jirovecii pneumonia (PJP), 4 episodes of other IFI and 154 non-IFI controls.. We found that (a) the BG overall sensitivity, specificity, positive predictive value and negative predictive value (NPV) were 87.9, 80.5, 76.7 and 89.9 %, respectively; (b) the highest sensitivity was found in the IC groups, followed by PJP, IA and other IFI groups; (c) an association was observed between BG kinetics and patients outcome; (d) in the IA episodes, the combination of BG or GM vs GM alone increased sensitivity from 60.0 to 83.3 % in the haematological patients; (e) false-positive BG results were related to Gram-negative infections or infusion of polyclonal IgM-enriched immunoglobulins, where high levels of BG were indeed detected.. Besides strengthening its overall good clinical performance, we provide evidence that serum BG correlates with clinical outcome and that, once used in combination with GM, BG allows to enhance IFI diagnosis rate. The high sensitivity and NPV, observed in the Intensive Care Unit setting, open to BG validation as a marker for assessment of antifungal treatment.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; beta-Glucans; Female; Fungemia; Galactose; Humans; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Proteoglycans; Sensitivity and Specificity; Serum; Young Adult

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections and a dysregulated inflammatory response. Infection-triggered hemophagocytic lymphohistiocytosis (HLH), which manifests itself as pathologic hyperactive inflammation, has been observed in subjects with CGD. However, there have been no reports of HLH as the initial presentation with subsequent diagnosis of CGD. Furthermore, the primary therapeutic strategy for HLH focuses on immunosuppressive therapies, which limits immune-mediated tissue damage. With immunodeficiency, this therapeutic strategy may worsen the outcome. This article discusses an 8-week-old Hispanic male who presented with fever of unknown origin. The initial diagnostic evaluation demonstrated pathologic hyperactive inflammation, meeting the HLH-2004 diagnostic criteria without an identified infectious etiology. Immunosuppressive therapy was initiated, with subsequent disseminated candida septic shock and sepsis-induced multisystem organ failure. Additional evaluations ultimately established the diagnosis of CGD. We transitioned to an immune-enhancing strategy with granulocyte and immunoglobulin infusions, and intensified antifungal therapies. These interventions ultimately led to the clearance of the fungal infection and the resolution of the hyperactive inflammatory state. This case represents the first reported case of HLH as the presenting finding leading to the subsequent diagnosis of CGD. It serves as a reminder that both immunodeficiency and inflammatory disorders may share features of pathologic hyperactive inflammation and highlights the conundrum that clinicians face when treating HLH in the setting of an unresolved infection. In this case report, we demonstrate that immune-enhancing therapies may aid in the control and the clearance of the infection, thus paradoxically decreasing the pathologic hyperactive inflammatory response.

Topics: beta-Glucans; Combined Modality Therapy; Diagnosis, Differential; Disease Progression; DNA Mutational Analysis; Fever of Unknown Origin; Fungemia; Granulocytes; Granulomatous Disease, Chronic; Humans; Immunization, Passive; Immunosuppressive Agents; Infant; Interferon-gamma; Lymphohistiocytosis, Hemophagocytic; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Opportunistic Infections; Proteoglycans

Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain ; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected.

Topics: Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Biomarkers; Echinocandins; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Micafungin; Multiple Organ Failure; Scedosporium; Treatment Failure

Topics: Adolescent; Adult; Aged; beta-Glucans; Biomarkers; Female; Fungemia; Humans; Japan; Male; Middle Aged; Prognosis; Retrospective Studies; Trichosporon; Trichosporonosis; Young Adult

The detection of serum 1,3-β-d-glucan (BDG) has been reported to be useful for the diagnosis and therapeutic monitoring of various invasive fungal infections. Although Trichosporon fungemia is increasingly recognized as a fatal mycosis in immunocompromised patients, the utility of this assay for Trichosporon fungemia is still unknown. In our experience (28 cases), the level of BDG rose in about half of the patients with hematologic disorders who developed Trichosporon fungemia. Among them, early death from this infection was more frequently seen in BDG-negative patients than in BDG-positive patients. In addition, overall survival was also significantly worse in BDG-negative patients than in BDG-positive patients. There were no significant differences between these two patient groups in terms of clinical background. Unlike for other invasive fungal infections, elevation of BDG level may indicate a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; beta-Glucans; Echinocandins; Female; Fluconazole; Fungemia; Hematologic Diseases; Humans; Immunocompromised Host; Lipopeptides; Male; Micafungin; Miconazole; Middle Aged; Proteoglycans; Retrospective Studies; Treatment Outcome; Trichosporon; Young Adult

Topics: Antifungal Agents; beta-Glucans; Fungemia; Humans; Polysaccharides; Proteoglycans; Trichosporonosis

The detection of 1,3-β-D-glucan serum levels may permit establishing the diagnosis of invasive fungal infections more early. We tested in six healthy volunteers whether the intake of a 1,3-β-D-glucan-containing nutritional supplement leads to false-positive 1,3-β-D-glucan levels. All levels were negative, even in two different dosing regimens.

Topics: Adult; beta-Glucans; Diet; False Positive Reactions; Female; Fungemia; Humans; Immunoassay; Male; Mycology; Proteoglycans; Serum

The aim was to evaluate the role of procalcitonin (PCT) and (1-3)-β-D-glucan (BG) tests for early detection or exclusion of central venous catheter-related bloodstream infections (CRBSI) in patients after orthotopic liver transplantation (OLT).. Fifty-five patients with clinically suspected CRBSI were assessed after OLT in this prospective study. On the day of clinical suspicion of CRBSI, blood samples were obtained from central venous catheters and a peripheral vein for blood cultures and from a peripheral vein for PCT and BG tests. Plasma PCT and BG values were measured by using an immunoluminometric assay and Fungitell BG assay, respectively. No prisoners or organs from prisoners were used in this study.. Twenty-five patients (45%) were diagnosed with CRBIS. Among them, 13 (52%) displayed gram-positive bacteriemia, 11 (44%) gram-negative bacteriemia, and 1 (4%) fungemia. The PCT values were higher in CRBSI than in non-CRBSI patients (P = .003). CRBSI patients did not show significant increases in plasma BG values compared with non-CRBSI subjects (P = .051). PCT and BG area under receiver operating characteristic curves were 0.840 and 0.486, respectively. Sensitivity, specificity, and positive and negative predictive values of a PCT of ≥ 3.1 ng/mL for the diagnosis of CRBSI were 0.72, 0.87, 0.82, and 0.79, respectively. The figures for a BG of ≥ 83 pg/mL were 0.32, 0.90, 0.73, and 0.61, respectively. Among the 24 patients with bacteria infections, PCT was higher in patients with gram-negative than those with gram-positive bacterial infections (P = .022).. We concluded that the PCT assay may be a useful rapid diagnostic adjunct for the diagnosis of suspected CRBSI in OLT patients.

Topics: Bacteremia; beta-Glucans; Calcitonin; Calcitonin Gene-Related Peptide; Catheters, Indwelling; Fungemia; Humans; Liver Transplantation; Protein Precursors; Proteoglycans

The plasmatic levels of 1,3-beta-d-glucan (BDG) were >523 pg/ml in 4 children, 2 low-birth-weight neonates and 2 stem cell transplant recipients, with the following invasive fungal diseases (IFD) proven apart from this BDG test: 3 cases of Candida parapsilosis candidemias and 1 case of disseminated aspergillosis. The BDG test may be useful for identification of IFD in pediatrics.

Topics: Aspergillosis; Aspergillus; beta-Glucans; Candida; Candidiasis; Child; Female; Fungemia; Humans; Immunocompromised Host; Infant, Newborn; Male; Proteoglycans

Diagnosis of invasive fungal infection (IFI) remains a challenge. A retrospective study was performed on 279 patients at three French university hospitals to evaluate the performance of the (1-->3)-beta-D-glucan assay (BG assay; Fungitell; Associates of Cape Cod, Inc.) for the diagnosis of IFI. The results of one serum per subject were analyzed for 117 patients who had probable or proven IFI according to the European Organization for Research and Treatment of Cancer criteria (70 invasive pulmonary aspergilloses [IPA], 27 fungal bloodstream infections, and 20 Pneumocystis jiroveci pneumonias), 40 blood donors, and 122 patients who were hospitalized in hematology wards or intensive care units and were at risk for IFI but in whom IFI had not been diagnosed. For the overall IFI diagnosis, the BG assay had 77.8% sensitivity and specificities of 92.5 and 70.5% for blood donors and patients at risk, respectively. The assay was positive in 48 patients with IPA (68%), in 23 with bloodstream infections (85.2%), and in all who had P. jiroveci pneumonias (100%), and the false-positive rate varied depending on the controls used. It allowed a higher rate of detection among IPA patients compared to the galactomannan enzyme-linked immunosorbent assay (ELISA) (48 versus 39 patients, respectively) and among candidemia patients compared to the mannan ELISA (20 versus 11 patients, respectively). This assay therefore appears to be useful in the diagnosis of IFI, particularly for serum analysis of pneumocystosis pneumonia patients, but further studies are needed to evaluate false-positive rates and its future role in IFI diagnosis.

Topics: Aspergillosis; beta-Glucans; Blood Donors; Candidiasis; False Positive Reactions; France; Fungemia; Hospitals, University; Humans; Lung Diseases, Fungal; Mycoses; Pneumonia, Pneumocystis; Proteoglycans; Reagent Kits, Diagnostic; Sensitivity and Specificity

Invasive fungal infections (IFIs) are life-threatening complications in neutropenic patients with hematological malignancies. Because early diagnosis of IFI is difficult, new noninvasive, culture-independent diagnostic tools are needed to improve clinical management. Recent studies have reported that detection of 1,3-beta-D-glucan (BG) antigenemia may be useful for diagnosis of IFI. The aim of the present prospective study was to evaluate the usefulness of monitoring BG in patients undergoing chemotherapy for acute leukemia.. BG antigenemia was measured by a colorimetric assay twice weekly in the absence of fever and daily in the presence of fever. IFIs were classified according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group.. During 190 consecutive neutropenic episodes (median duration, 22 days; range, 7-113 days) in 95 patients, 30 proven or probable IFIs (13 aspergillosis, 15 candidiasis, and 2 mixed IFIs) were diagnosed. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of 2 consecutive BG values > or =7 pg/mL for diagnosis of proven or probable IFI was 0.63 (95% confidence interval, 0.44-0.79), 0.96 (95% confidence interval, 0.89-0.98), 0.79 (95% confidence interval, 0.57-0.92), 0.91 (95% confidence interval, 0.84-0.95), and 0.89, respectively. The time interval between onset of fever as first sign of IFI and BG antigenemia was significantly shorter than the time to diagnosis of IFI by clinical, microbiological, radiological, and/or histopathological criteria (P < .001). BG values >50 pg/mL were observed in only 2 patients, both of whom experienced failure of antifungal therapy.. Monitoring of BG antigenemia is a useful noninvasive method for early diagnosis of IFI in patients with acute leukemia.

Topics: Adult; Aged; Antigens, Fungal; Aspergillosis; beta-Glucans; Candidiasis; Female; Fungemia; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Proteoglycans; Sensitivity and Specificity

The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum beta-D-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9+/-29.6 and 95.8 pg ml(-1), respectively, for patients with IFI and 64.4+/-17.1 and 32.9 pg ml(-1) for patients with only AUNF (P<0.0001). The differences remained significant over the 10 days despite antifungal therapy. The occurrence of > or =2 sequential concentrations of > or =80 pg ml(-1) ('positive' test) was found to give the best overall option for diagnosis, with an accuracy of 81.3%, sensitivity of 86.8%, positive predictive value of 76.7% and negative predictive value of 86.5%. Of the patients with an IFI, 78% developed a positive test at or before the clinical diagnosis was made -- this occurred at a mean (range) of 1.25 (-14 to +14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50% of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30% of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.

Topics: Adolescent; Adult; Antifungal Agents; Antigens, Fungal; beta-Glucans; Female; Fever; Fungemia; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycoses; Neutropenia; Predictive Value of Tests; Sensitivity and Specificity

We evaluated the Fungitell beta-glucan (BG) test with specimens from patients with presumed histoplasmosis. The sensitivity of the test was 87% in histoplasmosis cases and had a specificity of 68% with controls. Histoplasmosis should be considered as a possible cause for a positive BG test, but such results may be found with many other conditions that are clinically similar to this fungal disease. Therefore, there is a need to conduct confirmatory tests for histoplasmosis in the appropriate clinical setting.

Topics: Antigens, Fungal; beta-Glucans; Fungemia; Histoplasma; Histoplasmosis; Humans; Lung Diseases, Fungal; Proteoglycans; Sensitivity and Specificity; Serologic Tests

The prevalence of invasive fungal infection is increasing. An effective diagnostic test is required to identify and treat them successfully.. All autopsy records at our hospital for the period from January 2000 through December 2005 [corrected] were reviewed for cases of invasive fungal infection. The diagnostic efficacy of a serum (1-->3)-beta-D-glucan (beta-glucan) assay was examined using only those cases in which patients had been tested for fungal infection within 2 weeks before death.. Of 456 autopsies, 54 (11.8%) involved cases of invasive fungal infection. Leukemias were the most frequent underlying disease (in 52% of cases of invasive fungal infection), and Aspergillus species was the most frequent pathogen detected (in 70%). Of the 54 patients with invasive fungal infection, 41 had beta-glucan testing performed within 2 weeks before death, as did 63 patients without invasive fungal infection; 48 of 54 patients with invasive fungal infection had a blood culture performed. The sensitivity and specificity of the beta-glucan test for the detection of invasive fungal infection were 95.1% and 85.7%, respectively, with a cutoff value of 30 pg/mL; 85.4% and 95.2%, respectively, with a cutoff value of 60 pg/mL; and 78.0% and 98.4%, respectively, with a cutoff value of 80 pg/mL. The sensitivity of blood culture testing was 8.3%. With a prevalence of 11.8%, the positive and negative predictive values for the beta-glucan test were 47.1% and 99.2%, respectively, with a cutoff of 30 pg/mL; 70.4% and 98.0%, respectively, with a cutoff of 60 pg/mL; and 86.7% and 97.1%, respectively, with a cutoff of 80 pg/mL. During the 6-year period studied, of 21 patients with fungus-positive blood cultures that were preceded or followed by a beta-glucan test within 2 weeks, 4 had negative beta-glucan test results (beta-glucan level, <30 pg/mL), and 17 had positive results (beta-glucan level, >60 pg/mL); the concordance between culture results and beta-glucan test results was 81.0%. Contrary to the general belief, 5 of 6 cases of cryptococcemia were associated with high serum beta-glucan levels.. The beta-glucan test is an effective diagnostic tool for invasive fungal infection.

Topics: Autopsy; beta-Glucans; Blood; Fungemia; Fungi; Humans; Mycoses; Predictive Value of Tests; Proteoglycans; Sensitivity and Specificity; Statistics as Topic

For the rapid diagnosis of systemic Candida infection, we compared the performance of an established seminested polymerase chain reaction (snPCR), serological tests for (1 --> 3)-beta-D-glucan assay and Candida mannan antigen assay, and blood culture in our murine model for Candida albicans translocation. In this mouse model, C. albicans disseminated to the liver from the intestine after day 6.5; the snPCR and blood culture results became positive from days 8 to 8.5 in about 60% of infected mice with culture-proven translocation, and in 100% on day 9. Both (1 --> 3)-beta-D-glucan and Candida mannan antigen were elevated in the serum as early as day 6.5 of infection, though they did not identify Candida species. Because the established snPCR can differentiate four clinically important Candida species and conventional microbiological methods require at least 48 h to identify Candida species in blood samples, the snPCR assay is advantageous for rapidly identifying Candida species in the blood. Therefore, the combination of the serological assays and the snPCR seems to be valuable for the early diagnosis of systemic C. albicans infection.

Topics: Animals; Bacterial Translocation; beta-Glucans; Blood; Candida albicans; Candidiasis; Disease Models, Animal; DNA, Bacterial; Feces; Fungemia; Liver; Mannans; Mice; Polymerase Chain Reaction; Proteoglycans; Sensitivity and Specificity; Serologic Tests

Candidemia is a major infectious complication of seriously immunocompromised patients. In the absence of specific signs and symptoms, there is a need to evolve an appropriate diagnostic approach. A number of methods based on the detection of Candida mannan, nucleic acid and (1,3)-beta- D- glucan (BDG) have been used with varying specificities and sensitivities. In this retrospective study, attention has been focused to evaluate the usefulness of two or more disease markers in the diagnosis of candidemia.. Diagnostic usefulness of Platelia Candida Ag for the detection of mannan, Platelia Candida Ab for the detection of anti-mannan antibodies, Fungitell for the detection of BDG, and of a semi-nested PCR (snPCR) for the detection Candida species-specific DNA have been retrospectively evaluated using 32 sera from 27 patients with culture-proven candidemia, 51 sera from 39 patients with clinically suspected candidemia, sera of 10 women with C. albicans vaginitis, and sera of 16 healthy controls.. Using cut-off values recommended by the manufacturers, the sensitivity of the assays for candidemia patients were as follows: Candida snPCR 88%, BDG 47%, mannan 41%, anti-mannan antibodies 47%, respectively. snPCR detected 5 patients who had candidemia due to more than one Candida species. The sensitivities of the combined tests were as follows: Candida mannan and anti-mannan antibodies 75%, and Candida mannan and BDG 56%. Addition of snPCR data improved the sensitivity further to 88%, thus adding 10 sera that were negative by BDG and/or mannan. In clinically suspected, blood culture negative patients; the positivities of the tests were as follows: Candida DNA was positive in 53%, BDG in 29%, mannan in 16%, and anti-mannan antibodies in 29%. The combined detection of mannan and BDG, and mannan, BDG and Candida DNA enhanced the positivity to 36% and 54%, respectively. None of the sera from Candida vaginitis patients and healthy subjects were positive for Candida DNA and mannan.. The observations made in this study reinforce the diagnostic value of snPCR in the sensitive and specific diagnosis of candidemia and detection of more than one Candida species in a given patient. Additionally, in the absence of a positive blood culture, snPCR detected Candida DNA in sera of more than half of the clinically suspected patients. While detection of BDG, mannan and anti-mannan antibodies singly or in combination could help enhancing sensitivity and eliminating false positive tests, a more extensive evaluation of these assays in sequentially collected serum samples is required to assess their value in the early diagnosis of candidemia.

Topics: Antibodies, Fungal; Antibody Specificity; Antigens, Fungal; beta-Glucans; Candida; Candidiasis; DNA, Fungal; Fungemia; Immunoassay; Immunoenzyme Techniques; Mannans; Polymerase Chain Reaction; Proteoglycans; Reagent Kits, Diagnostic; Retrospective Studies; Sensitivity and Specificity

Most invasive fungal infections such as candidemia are frequent in patients with hematologic malignancies. We measured cytokines/chemokines (IL-6, IL-8, monocytic chemoattractant protein 1, RANTES and epithelial neutrophil-activating peptide 78), soluble molecules (sFas, sE-selectin and soluble vascular cell adhesion molecule 1) and platelet activation markers (soluble CD40 ligand, sP-selectin and platelet-derived microparticles) in patients with hematologic malignancies under prophylactic treatment with an antifungal drug (fosfluconazole). We classified patients into 2 groups by the level of beta-D-glucan. The level of C-reactive protein was higher in the high beta-D-glucan group (>5 pg/ml) than in the low beta-D-glucan group. However, there were no differences in the levels of other parameters (peripheral blood cells, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, blood urea nitrogen and creatinine). Patients in the high beta-D-glucan group exhibited a significant elevation of several chemokines, soluble molecules and platelet activation markers compared with those in the low beta-D-glucan group, but the levels of IL-8, monocytic chemoattractant protein 1 and sFas did not differ significantly. The levels of C-reactive protein and IL-6 increased significantly after 1 or 2 weeks on fosfluconazole in both groups. In contrast, the high beta-D-glucan group exhibited a significant decrease in chemokines, soluble markers and platelet-derived microparticles compared with the low beta-D-glucan group after treatment with fosfluconazole, although the patients in the low beta-D-glucan group exhibited no significant changes. Furthermore, the levels of RANTES, epithelial neutrophil-activating peptide 78, soluble vascular cell adhesion molecule 1 and sE-selectin correlated positively with platelet-derived microparticles in the high beta-D-glucan group. These findings suggest that fungal infection may modulate the vascular events in which some platelet-related chemokines are involved.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Biomarkers; Candidiasis; Cell Adhesion Molecules; Chemokines; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Organophosphates; Platelet Activation; Prodrugs

Endotoxemia has been reported as a mechanism for the fatal sequela after heatstroke. Subsequent disseminated fungal infection in a heatstroke patient has been also described. Beta-D-glucan, a constituent of the fungal cell wall, is an early diagnostic measure for fungal infection. In a heatstroke case, we examined for the first time levels of serum beta-d-glucan and endotoxin. A 34-year-old man with a body temperature of 43.5 degrees C was admitted in a state of shock. Prior to the development of disseminated intravascular coagulopathy (DIC), a remarkable elevation of serum beta-D-glucan level to 116 pg/mL (normal level<6.0 pg/mL) was revealed on the first day of admission. However, serum endotoxin was not detected when using a method that excluded beta-D-glucan contamination from endotoxin measurement (normal level<1.0 pg/mL). This change of beta-D-glucan level was accompanied by a depressed neutrophil function, especially in phagocytosis of 34% (normal range 70-90%) but not in bacterocidal function (81% versus a normal range of 70-100%). After intensive care including continuous hemodiafiltration, the patient regained consciousness but remained ataxic due to cerebellar infarction, which might have resulted from DIC, and subsequent bilateral fungal oculitis were revealed 45 days after admission. This case report demonstrates the elevation of serum beta-D-glucan but normal endotoxin levels after heatstroke, which may prompt further study to re-examine the serum levels of endotoxin in such catastrophic insults.

Topics: Adult; beta-Glucans; Brain Infarction; Cerebellar Diseases; Cerebellum; Disseminated Intravascular Coagulation; Endotoxins; Eye Infections, Fungal; Fungemia; Heat Stroke; Humans; Male; Neutrophils; Phagocytosis

The Fungitell assay (Associates of Cape Cod, Inc.) is a commercial test that detects (1-3)-beta-D-glucan (BG) and is intended for diagnosis of invasive fungal infections. To evaluate the Fungitell assay, we tested serum and plasma samples from healthy blood donors and from patients with blood cultures positive for yeast or bacteria. All 36 blood donors were BG negative, and 13 of 15 candidemic patients were BG positive. Of 25 bacteremic patients, 14 (10 with gram-positive bacteremia) were BG positive. One of the latter patients with Staphylococcus aureus bacteremia also had invasive candidiasis, based on histological findings in a tissue biopsy; therefore, the BG result was a true positive. The sensitivity, specificity, and positive and negative predictive values of the Fungitell assay, by patient, for these three groups were 93.3%, 77.2%, 51.9%, and 97.8%, respectively. We also performed the Fungitell assay on sera that had been tested for Aspergillus galactomannan or Histoplasma antigen. All six Histoplasma antigen-positive patients and 31 of 32 Aspergillus galactomannan-positive patients were also BG positive. BG results for the 10 Histoplasma antigen-negative and the 32 Aspergillus galactomannan-negative patients varied, but we were unable to confirm many of the results. Between-run coefficients of variance (CVs) for the assay ranged from 3.2% to 16.8%; within-run CVs were < or =4.8%. The correlation coefficient for an interlaboratory reproducibility study was 0.9892. Concentrations of hemoglobulin, bilirubin, and triglycerides that caused 20% interference were 588, 72, and 466 mg/dl, respectively. Our results suggest that the Fungitel assay may be most useful for excluding invasive fungal infection.

Topics: Aspergillosis; Aspergillus; beta-Glucans; Candidiasis; Fungemia; Histoplasma; Histoplasmosis; Humans; Reagent Kits, Diagnostic; Reproducibility of Results

The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

Topics: Adult; beta-Glucans; Candidiasis; Fungemia; Humans; Leukemia, Myeloid, Acute; Limulus Test; Mycoses; Myelodysplastic Syndromes; Neutropenia; Polysaccharides; Predictive Value of Tests; Proteoglycans; Reagent Kits, Diagnostic; Sensitivity and Specificity

We evaluated the clinical usefulness of a polymerase chain reaction (PCR) assay amplifying the 18S ribosomal RNA gene of fungi for the diagnosis of deep candidiasis, compared with that of the beta-glucan test or Cand-Tec test. Thirty critically ill patients who had received prolonged care with intravenous hyperalimentation and endotracheal intubation in the intensive care unit and were suspected of having deep fungal infections were examined. Twenty-one were fungi positive in the PCR assay (70%). Among 24 samples in which the PCR assay, beta-glucan test and Cand-Tec test were performed simultaneously, 75% of the samples (18/24) were fungi positive in the PCR assay, whereas only 54% (13/24) had positive reactions in the beta-glucan test and 21% (5/24) in the Cand-Tec test. The results of the Cand-Tec test showed no relationship with those of the PCR or beta-glucan test. The lower limit of detection in the PCR assay was 4-5 CFU/ml of C. albicans in blood. No fungal organism was amplified from the serum of 20 healthy individuals. The results of the PCR assay and beta-glucan test showed a significant correlation in this study, but the PCR assay proved to be more sensitive than the beta-glucan test (p < 0.05), and to be more useful for the clinical diagnosis and monitoring of deep Candidiasis.

Topics: beta-Glucans; Candida; Candidiasis; Colony Count, Microbial; DNA Primers; DNA, Fungal; Electrophoresis, Agar Gel; Female; Fungemia; Genes, Fungal; Glucans; Humans; Male; Polymerase Chain Reaction; Reproducibility of Results; RNA, Fungal; RNA, Ribosomal, 18S; Sensitivity and Specificity

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; beta-Glucans; Candidiasis; Cryptococcosis; Diagnostic Errors; Evaluation Studies as Topic; Female; Fungemia; Glucans; Humans; Kinetics; Limulus Test; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Nephelometry and Turbidimetry; Time Factors; Urinary Tract Infections

(1-->3)-beta-D-glucan is a characteristic fungal cell-wall constituent. To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G, a horseshoe-crab coagulation enzyme that is extremely sensitive to this polysaccharide. With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%). All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%). Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL. With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% (172/202). The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections. Causative fungi included candida, aspergillus, cryptococcus, and trichosporon. Determination of plasma (1-->3)-beta-D-glucan with factor G is a highly sensitive and specific test for invasive deep mycosis and fungal febrile episodes, and will substantially benefit immunocompromised patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; beta-Glucans; Blood Coagulation Factors; Candidiasis; Child; Child, Preschool; Female; Fever; Fungemia; Glucans; Humans; Male; Middle Aged; Mycoses; Sensitivity and Specificity; Serine Endopeptidases