epiglucan and Hematologic-Diseases

Topics: Antifungal Agents; Aspergillosis; beta-Glucans; Biomarkers; Candidiasis; Galactose; Hematologic Diseases; Humans; Immunocompromised Host; Lung Diseases, Fungal; Mannans; Molecular Diagnostic Techniques; Mycoses

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

We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.

Topics: Adolescent; Adult; Aged; beta-Glucans; Biomarkers; Diagnostic Tests, Routine; Female; Galactose; Gliotoxin; Hematologic Diseases; Humans; Invasive Fungal Infections; Male; Mannans; Middle Aged; Prospective Studies; Proteoglycans; Sensitivity and Specificity; Serum; Sugar Alcohols; Urinalysis; Young Adult

Detection of the fungal cell wall component beta-glucan (BG) in serum is increasingly used to diagnose invasive fungal infections (IFI), but its optimal use in hematology patients with high risk of IFI is not well defined. We retrospectively analyzed the diagnostic accuracy, optimal cut-off level, and potential confounding factors of BG reactivity. The inclusion criteria were: adult patients with hematologic disease who were admitted to the hematology ward during the 2-year study period and who had two or more consecutive BG assays performed. In total, 127 patients were enrolled. Thirteen patients with proven or probable IFI, as defined by the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, were identified. Receiver operating characteristic (ROC) curve analysis showed a high overall diagnostic performance (area under the ROC curve = 0.98) and suggested an optimal cut-off level of 158 pg/ml, with a sensitivity and a specificity of 92 % and 96 %, respectively. Multiway analysis of variance indicated that treatment with pegylated asparaginase (p < 0.001), admission to the intensive care unit (ICU; p = 0.0007), and treatment with albumin, plasma, or coagulation factors (p = 0.01) are potential confounding factors of BG reactivity. We propose that a higher cut-off level than that recommended by the manufacturer should be used to monitor adult hematology patients at high risk for IFI. Our results also suggest that elevated BG levels in patients treated with pegylated asparaginase, albumin, plasma, or coagulation factors, or those admitted to the ICU should be interpreted with caution.

Topics: Adolescent; Adult; Aged; beta-Glucans; Data Interpretation, Statistical; Diagnostic Tests, Routine; False Positive Reactions; Female; Hematologic Diseases; Humans; Male; Middle Aged; Mycoses; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Serum; 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

The invasive fungal infections (IFI) in immunocompromised patients are associated with a high mortality rate and diagnostic difficulty. Serological methods such as aspergillus galactomannan assay (GM test) and (1, 3)-beta-D glucan (BG) assay (G test) can be used as an adjunctive method for IFI diagnosis based on their characteristics of easy-operating, rapidness and high sensitivity. Compared with GM test, G test can be more widely used except for the diagnosis of aspergillosis. The purpose of this study was to investigate the value of G test in the diagnosis of IFI in patients with hematological disorders. The plasma was collected from 162 suspected IFI patients with hematological disorders in Beijing Daopei Hospital, including 85 patients after chemotherapy and 77 patients after stem cell transplantation from May 2007 to May 2008, BG level was measured with MB-80 Microbiology Kinetic Rapid Reader and the measured results together with the clinical characteristics were retrospectively analyzed. According to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, there were 2 patients diagnosed as proven IFI, 18 as probable IFI, 75 as possible IFI and 67 as no IFI. The results showed that at a cutoff of 20 pg/ml, the sensitivity and specificity of G test were 75% and 91% respectively, with a positive predictive value (PPV) of 71.4% and a negative predictive value (NPV) of 92.4%. 51 out of the 75 possible IFI patients with elevated BG level were responsive to antifungal treatment but non responsive to broad-spectrum antibiotics, retrospectively were diagnosed as IFI, suggesting that G test improved the IFI diagnostic rate by 31.4%. In conclusion, G test is a rapid and simple method for early diagnosis of IFI in patients with hematological disorders.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Child; Female; Hematologic Diseases; Humans; Male; Middle Aged; Mycoses; Plasma; Young Adult

The establishment of an optimal noninvasive method for diagnosing invasive aspergillosis (IA) is needed to improve the management of this life-threatening infection in patients with hematological disorders, and a number of noninvasive tests for IA that target different fungal components, including galactomannan, (1-->3)-beta-d-glucan (BDG), and Aspergillus DNA, have been developed. In this study, we prospectively evaluated the diagnostic potential of three noninvasive tests for IA that were used in a weekly screening strategy: the double-sandwich enzyme-linked immunosorbent assay (ELISA) for galactomannan (Platelia Aspergillus), a real-time PCR assay for Aspergillus DNA (GeniQ-Asper), and an assay for BDG (beta-glucan Wako). We analyzed 149 consecutive treatment episodes in 96 patients with hematological disorders who were at high risk for IA and diagnosed 9 proven IA cases, 2 probable IA cases, and 13 possible invasive fugal infections. In a receiver-operating characteristic (ROC) analysis, the area under the ROC curve was greatest for ELISA, using two consecutive positive results (0.97; P = 0.036 for ELISA versus PCR, P = 0.055 for ELISA versus BDG). Based on the ROC curve, the cutoff for the ELISA could be reduced to an optical density index (O.D.I.) of 0.6. With the use of this cutoff for ELISA and cutoffs for PCR and BDG that give a comparable level of specificity, the sensitivity/specificity/positive predictive value/negative predictive value of the ELISA and the PCR and BDG tests were 1.00/0.93/0.55/1.00, 0.55/0.93/0.40/0.96, and 0.55/0.93/0.40/0.96, respectively. In conclusion, among these weekly screening tests for IA, the double-sandwich ELISA test was the most sensitive at predicting the diagnosis of IA in high-risk patients with hematological disorders, using a reduced cutoff of 0.6 O.D.I.

Topics: Adolescent; Adult; Aged; Aspergillosis; beta-Glucans; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Glucans; Hematologic Diseases; Humans; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Prospective Studies; ROC Curve; Sensitivity and Specificity

An assessment has been made regarding usefulness of measuring beta-D-glucan (beta-glucan) as fungal serodiagnosis in 50 cases of fungal infection with hematological diseases. Further, an assessment has been made regarding relation between hematological findings and therapeutic effect by administering miconazole, an antifungal agent (MCZ: Florid, clinically to the subjects. Positivity of beta-glucan (beta-glucan > or = 10 pg/ml) was observed in 54.5% (24/44), and the effective rate of MCZ in the positive cases was 75.0% (18/24). In the cases in whom fungus was detected, beta-glucan-positive rate was 50.0% (8/16), and MCZ-effective rate in beta-glucan-positive cases was 62.5% (5/8). The total effective rate of MCZ was 80% (40/50). Side effects were observed in 3 cases, but continual administration of MCZ was possible in all of the 3 cases. By the assessment regarding the relation between hematological findings and therapeutic effect of MCZ, it was found that the effective rates in the cases who underwent a transition with neutrophil and lymphocyte counts less than 500/microliters during the period of MCZ administration were 64.7% (11/17) and 50% (5/10), respectively, and large effects were observed in the cases who underwent a transition with the neutrophil and lymphocyte counts more than 500/microliters was 86.7% (19/22) and 91.7% (22/24), respectively. These results suggested that lymphocytes rather than neutrophils had an important role in the morbidity of fungal infection. It was noteworthy that MCZ was effective for the treatment of deep seated mycosis and significant effective rate was obtained in the group of patients who had neutrophils and lymphocytes less than 500/microliters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Child; Female; Glucans; Hematologic Diseases; Humans; Male; Miconazole; Middle Aged; Mycoses; Serologic Tests

The number of deep mycosis has been increasing because of increases in immunocompromised hosts and in fungal colonization associated with increasing use of broad-spectrum antibacterial antibiotics. Based on these phenomenon, a simple test method for an early diagnosis of deep mycosis is urgently desired. We therefore investigated the usefulness of assaying a fungal cell component, (1-->3)-beta-D-glucan (beta-glucan). The amount of beta-glucan was obtained from the difference between the amounts determined using Toxicolor and Endospecy, and the serum levels of more than 10 pg/ml were considered positive signs for beta-glucan. The following results were obtained: We found that beta-glucan was positive in 75% of the patients who had been definitely diagnosed to have mycosis, and in 58.3% of the patients strongly suspected of mycosis. The numbers of beta-glucan positive patients' in these 2 groups of patients were significantly different from that in those without mycosis (14.7%, P < 0.05). Thus a usefulness of beta-glucan measurement for the diagnosis of mycosis was demonstrated. However, beta-glucan was sometimes negative even in patients with fungemia at an early phase of the disease and turned positive several days later. Even in a patient with definite lung mycosis, who had a latent circumscribed lesion (afebrile and CRP-negative), beta-glucan was also negative. From these findings, one should be aware that the beta-glucan test produces false negatives even in patients with definite mycosis and that the test should be repeated during the course of the disease.

Topics: Aged; beta-Glucans; Female; Glucans; Hematologic Diseases; Humans; Immunocompromised Host; Limulus Test; Male; Middle Aged; Mycoses