galactomannan and Mycoses

Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.. We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.. Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.. Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.

Topics: Antifungal Agents; Chemotherapy-Induced Febrile Neutropenia; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Trees; Diagnostic Tests, Routine; Drug Administration Schedule; Drug Costs; Early Diagnosis; Epidemiologic Studies; Feasibility Studies; Galactose; Health Care Costs; Hematologic Neoplasms; Humans; Immunocompromised Host; Lung Diseases, Fungal; Mannans; Mycoses; Opportunistic Infections; Randomized Controlled Trials as Topic

Diagnosis of invasive fungal pneumonias by conventional culture methods is difficult to assess and often delayed. Nonmolecular fungal markers have emerged as an important adjunctive tool to support their diagnosis in combination with other clinical, radiologic, and microbiological criteria of invasive fungal diseases. Concerns about the sensitivity and specificity of some tests in different patient populations should lead to warnings about their widespread use. None can identify the emerging and particularly deadly fungal pathogens responsible for mucormycosis. The role of nonmolecular fungal markers should be better defined in combination with other microbiological and radiologic tools in preemptive antifungal strategies.

Topics: Biomarkers; Fungi; Galactose; Humans; Mannans; Mycological Typing Techniques; Mycoses; Respiratory Tract Infections; Sensitivity and Specificity

Topics: Antigens, Fungal; beta-Glucans; Candidiasis, Invasive; Galactose; Humans; Mannans; Mycoses; Proteoglycans; Pulmonary Aspergillosis; Serologic Tests

As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.

Topics: Antigens, Fungal; beta-Glucans; Biomarkers; Congresses as Topic; European Union; Galactose; Hematopoietic Stem Cell Transplantation; Leukemia; Mannans; Mycoses; Transplantation, Homologous

Invasive fungal infections are associated with high morbidity and mortality in critically ill patients due, in part, to diagnostic difficulties in the early stages. Nonculture-based techniques such as (1,3)-β-d-glucan, galactomannan, mannan and antimannan antibodies, Candida albicans germ tube-specific antibodies or fungal DNA are required for earlier diagnosis, prognostic information and monitoring outcome. A decision-tree algorithm based on the combination of nonculture-based techniques is suggested to optimize the diagnosis and evolution of critically ill patients at risk of invasive mycoses. The use of (1,3)-β-d-glucan and blood cultures twice a week is proposed; if positive, treatment initiation is recommended alongside the performance of the nonculture-based microbiological tool depending on suspected mycoses and the availability of techniques.

Topics: Antibodies, Fungal; Aspergillus; beta-Glucans; Candida; Decision Trees; DNA, Fungal; Galactose; Humans; Mannans; Mycoses; Proteoglycans; Serologic Tests

Antifungal prophylaxis in hematopoietic stem cell transplant recipients is a rapidly evolving field. For this prophylaxis to be beneficial and cost-effective, the risk of a life-threatening invasive fungal infection (IFI) should outweigh the risks of toxic effects and drug interactions introduced by the antifungal agent used. Not all hematopoietic stem cell transplant recipients have the same risk of IFIs. New prophylactic strategies using risk stratification and new broad-spectrum antifungals have the potential for reducing IFI-associated mortality in these patients. Further refinement of risk stratification and risk/benefit analysis (including pharmacoeconomic analysis) is needed. Stratification of IFI risk could be further sharpened based on emerging genetic and metabolic risk factors. However, 10 years after deciphering the human genome, it is unclear whether the genomic revolution would pay off for identifying the SCT recipients at highest risk for IFIs. Empiricism and reliance on institution-specific epidemiologic data are still expected to be a major part of the 'art and science' of risk stratification for fungal infections in SCT.

Topics: Antifungal Agents; Drug Monitoring; Fluconazole; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Mycoses

The (1→3)-β-D-Glucan (BG) assay has been approved for diagnosing invasive fungal disease (IFD). However, the test performance has been variable. We conducted a meta-analysis to determine the overall accuracy of BG assay for diagnosing IFD.. The sensitivity, specificity, and positive and negative likelihood ratios (PLR and NLR, respectively) of BG for diagnosing IFD were pooled using a bivariate meta-analysis. We also performed subgroup analyses.. Twelve reports, including 15 studies, were included for the analysis (proven and probable IFD vs possible or no IFD). The sensitivity, specificity, PLR and NLR were 0.76 (95% CI, 0.67-0.83), 0.85 (95% CI, 0.73-0.92), 5.05 (95% CI, 2.71-9.43), and 0.28 (95% CI, 0.20-0.39), respectively. Subgroup analyses showed that the BG assay had higher specificities for patients with hematological disorders and a positive BG result with two consecutive samples. The combination of galactomannan and BG increased the specificity value to 0.98 (95% CI, 0.95-0.99) for diagnosing invasive aspergillosis.. Serum BG determination is clinically useful for diagnosing IFD in at-risk patients, especially for hematology patients. The combination of galactomannan and BG was sufficient for diagnosing invasive aspergillosis. Since the BG assay is not absolutely sensitive and specific for IFD, the BG results should be interpreted in parallel with clinical findings.

Topics: Aspergillosis; beta-Glucans; Biomarkers; Candidiasis, Invasive; Galactose; Humans; Likelihood Functions; Linear Models; Mannans; Mycoses; Proteoglycans; ROC Curve; Sensitivity and Specificity

Fungal infections are of great relevance in surgical intensive care and Candida species represent the predominant part of fungal pathogens. Invasive aspergillosis is also relevant especially in patients with chronic pulmonary diseases. It is crucial for therapy success to begin adequate antifungal treatment at an early stage of the disease. Risk stratification of individual patient symptoms is essential for therapy timing. In case of suspected or proven candida infection, fluconazole is the agent of choice when the patient is clinically stable and no azoles have been administrated in advance and the local epidemiology makes azol resistance unlikely. For clinically instable patients with organ dysfunction the echinocandins serve as primary therapy because of their broad spectrum and reasonable safety profile. Due to a relevant proportion of azole resistant Candida species, susceptibility testing should be done routinely. Depending on the species detected de-escalating to an azole is feasible if organ dysfunctions have resolved. An invasive aspergillosis is primarily treated with voriconazole.

Topics: Adjuvants, Immunologic; Antifungal Agents; Azoles; beta-Glucans; Candidiasis; Critical Care; Cryptococcosis; Echinocandins; Galactose; Humans; Mannans; Mucus; Mycoses; Polyenes; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Tomography, X-Ray Computed

Topics: Antigens, Fungal; Aspergillus; Calcitonin; Candida; Galactose; Gram-Negative Bacteria; Humans; Lipopolysaccharides; Mannans; Microbiological Techniques; Molecular Diagnostic Techniques; Mycoses; Protein Precursors; Sepsis

This review summarizes recent developments in the diagnosis and treatment of fungal pneumonia, with an emphasis on invasive pulmonary aspergillosis.. Improvements in nonculture-based fungal diagnostics, early implementation of pulmonary high resolution, or spiral computed tomography scanning and a recent expansion of the antifungal armamentarium have greatly improved the outcome of immunocompromised patients with invasive aspergillosis. However, the field is changing: new pathogens (such as Zygomycetes) are emerging, and novel risk groups (ICU patients in particular) are being identified.. Galactomannan antigen detection is a valuable tool for evaluating patients at risk for invasive aspergillosis (as a screening assay on serum samples from neutropenic patients or as a confirmatory assay on bronchoalveolar lavage fluid samples, in general), but should be used in conjunction with modern imaging techniques. beta-D-Glucan and PCR assays are still investigational. Voriconazole is the drug of choice for invasive aspergillosis, whereas liposomal amphotericin B at 3 mg/kg per day is the preferred alternative in case of contraindication, drug-related side-effects, or intolerance. Whenever possible, optimal antifungal therapy should be complemented by surgical debridement of necrotic tissue. The added value of combination therapy is still unproven. Therapeutic drug monitoring of mold-active azoles should be implemented in order to minimize toxicity and maximize efficacy. Lipid-based formulations of amphotericin B, and to a lesser extent voriconazole, are the drugs of choice for non-Aspergillus related fungal pneumonia. Although active in prophylaxis, the efficacy of posaconazole in confirmed infections remains controversial.

Topics: Amphotericin B; Antifungal Agents; Fungi; Galactose; Humans; Mannans; Mycoses; Pneumonia; Pulmonary Aspergillosis; Pyrimidines; Radiography, Thoracic; Triazoles; Voriconazole

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

Early diagnosis of fungal infections and the implementation of appropriate treatment represent major issues for clinicians, nowadays. Histopathological demonstration of microorganisms in tissue specimens or growth of fungal agents in culture media is still considered the "gold standard", but obtaining such specimens may be difficult. Several groups have investigated serological assays for cell wall elements unique to fungal organisms in serum or other body fluids to improve diagnostics in patients with haematological malignancies or undergoing haematopoietic stem-cell transplantation. In this review we have concentrated on the currently available assays allowing for detection of highly immunogenic components of fungal cell wall: galactomannan, mannan, and also (1-->3)-beta-D-glucan. Rapid serological tests appear to be useful for screening high-risk haematological patients, since they allow for the early diagnosis of invasive fungal infections, including infections with the most common pathogens such as Aspergillus and Candida. Based on current literature, factors increasing the probability of obtaining false-positive or false-negative results detected by each test were also analysed and tabulated.

Topics: Antigens, Fungal; beta-Glucans; Body Fluids; Galactose; Humans; Mannans; Mycoses; Proteoglycans; Serologic Tests

Early treatment of invasive mold infections improves the outcome. Therapy is often delayed, however, because available diagnostic tools such as culture, microscopy and conventional radiology lack sensitivity; consequently, empirical initiation of antifungal therapy has been advocated, particularly for patients with prolonged unexplained neutropenic fever.. Much recent progress has been made in the development and evaluation of nonculture-based assays, including the detection of the fungal antigens galactomannan and beta-D-glucan and the detection of fungal DNA by polymerase chain reaction techniques. These new tools should aid the rapid, early diagnosis of invasive fungal disease, especially when used as screening tools in conjunction with sensitive imaging techniques.. The review will consider these recent developments with the purpose of introducing the concept of preemptive antifungal therapy.

Topics: Antifungal Agents; Antigens, Fungal; beta-Glucans; Diagnostic Imaging; DNA, Fungal; Galactose; Humans; Mannans; Mycoses; Proteoglycans

The early treatment of invasive fungal infection is critical but is hampered by the non-specific nature of clinical and radiological signs and the insensitivity of current laboratory diagnostic methods. If mortality due to invasive fungal infection is to be reduced, new, preemptive therapeutic strategies, targeting those patients at highest risk, are required and these will depend on the development of rapid, sensitive diagnostic methods. Such methods have become available in the form of high-resolution computed tomography scanning and serological and molecular techniques and in this review the authors describe recent studies assessing the utility of these methods and consider their role in management strategies.. Sensitive assays for the detection of fungal DNA and antigens such as galactomannan and glucan have been prospectively evaluated in the clinical setting and enable identification of patients at an earlier stage of infection. However, the sensitivity and specificity of the assays vary considerably in different studies, depending on several factors including patient selection and clinical application of the test, and issues regarding the release and circulation of galactomannan and fungal DNA remain to be clarified.. Rapid serological and molecular diagnostic methods facilitate the early diagnosis of invasive fungal infection and would appear to be most useful when used prospectively to screen high-risk patients. However, in order to determine the optimal approach to treatment it is essential that these tests are incorporated into management strategies and their impact on incidence of invasive fungal infection and clinical outcome evaluated in further clinical trials.

Topics: Antifungal Agents; Galactose; Glucans; Humans; Mannans; Mycoses; Polymerase Chain Reaction; Tomography, X-Ray Computed

Invasive deep mycoses following bone marrow and solid-organ transplantation remain a major cause of morbidity and mortality. Species of Candida and Aspergillus account for more than 80% of these mycoses. Because these infections are often difficult to diagnose and treat successfully, antifungal prophylaxis is recommended in high-risk patients. Fluconazole is useful in patients who are at risk of invasive candidiasis, including bone marrow transplants, liver and pancreatic transplants. Although invasive aspergillosis is frequent in patients with bone marrow, lung and heart transplantation, no established methods have been available for its prophylaxis. Recently, efforts to improve the efficiency of diagnostic tests have been directed toward the detection of fungal components or metabolites. The requirements for clinical use (monitoring) are as follows: capability of early diagnosis, quantitative measurement, and easy sampling and simple assay procedure. The detection of plasma (1-3)-beta-D-glucan (BDG), a characteristic cell wall component of almost all fungi, is widely used in Japan. Twenty-seven episodes of fungemia were observed in our hematology ward and all were positive with BDG. Positive results were observed before the documentation of fungemia in 14 patients (51.9%). Although the positive rate of BDG also was 100% in 17 patients with invasive aspergillosis, it rose slightly at an early stage of the disease in 13 patients (76.5%). The determination of plasma BDG appears useful in the monitoring of deep fungal infection, but its usefulness for early diagnosis remains to be determined. The utility of detection of Aspergillus galactomannan by ELISA and fungal DNA by polymerase chain reaction are also discussed.

Topics: Animals; Antifungal Agents; Antigens, Fungal; beta-Glucans; Biomarkers; Galactose; Glucans; Humans; Mannans; Monitoring, Physiologic; Mycoses; Organ Transplantation; Polymerase Chain Reaction; Postoperative Complications

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-β-D-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31% achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7% of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as "not classified" compared with "possible invasive fungal disease" according to the EORTC/MSG criteria. Moreover, six "not classified" patients were positive for either plasma (1-3)-β-D-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-β-D-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections.

Topics: Adolescent; Adult; Aged; Antibiotic Prophylaxis; Antifungal Agents; Antigens, Fungal; Febrile Neutropenia; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Mycoses; Prospective Studies; Pyrimidines; Triazoles; Voriconazole; Young Adult

Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment.. Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines.. Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm.. A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Fever; Galactose; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Prospective Studies; Pyrimidines; Radiography, Thoracic; Risk Factors; Singapore; Tomography, X-Ray Computed; Treatment Outcome; Triazoles; Voriconazole

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of β-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Bacterial; Aspergillosis; beta-Glucans; Candidiasis, Invasive; Chemical and Drug Induced Liver Injury; Early Diagnosis; Echinocandins; Female; Galactose; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lymphoma; Male; Mannans; Micafungin; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Disease-Free Survival; Double-Blind Method; Drug Monitoring; Fluconazole; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Middle Aged; Mycoses; Myeloablative Agonists; Survival Rate; Transplantation, Homologous; Young Adult

The prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3-beta-D-glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells.. A cross-sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman's correlation coefficient, ROC curve analysis and 2 × 2 contingency table.. Serum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut-off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut-off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection.. The immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Aspergillus; beta-Glucans; Cross-Sectional Studies; Female; Follow-Up Studies; Galactose; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Mycoses; Prognosis; Young Adult

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Bronchoalveolar Lavage Fluid; Female; Galactose; Humans; Male; Mannans; Medical Overuse; Middle Aged; Mycoses; Retrospective Studies; Young Adult

Galactomannan index (GMI) at a level higher than 0.5 provides high sensitivity and specificity for the diagnosis of fungal peritonitis. Here, we report the false-positive of GMI in peritoneal dialysis (PD) effluent (PDE) due to Rhodococcus peritonitis in PD patients.. GMI in PDE of case #1 and case #2 were 1.53 and 0.76, respectively, while serum GMI of both cases was less than 0.5. In addition, GMI from the specimens obtained directly from the stationary phase of Rhodococcus colonies were 1.27 and 1.56, which were isolated from case #1 and #2, accordingly.. High GMI in PDE of PD patients is not specific just for fungal infections but may also be secondary to other infections, such as Rhodococcus spp., especially in endemic areas.

Topics: Actinomycetales Infections; Aged; Biomarkers; Diagnosis, Differential; False Positive Reactions; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Patient Selection; Peritoneal Dialysis; Peritonitis; Renal Insufficiency, Chronic; Rhodococcus

A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes.. This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf).. Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%,. Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

Topics: Adult; Aged; Antifungal Agents; Biomarkers; Feasibility Studies; Female; Galactose; Guideline Adherence; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia; Male; Mannans; Mass Screening; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Practice Guidelines as Topic; Retrospective Studies; Treatment Outcome

Antifungal posaconazole prophylaxis for AML patients receiving induction chemotherapy has been routine at our centre since 2009. This retrospective study examined the feasibility and practicability of our prophylaxis guidelines in clinical practice. Data sets of 90 patients undergoing induction-chemotherapy for AML between 2011 and 2014 were evaluated regarding adherence to local guidelines for the administration of antifungal prophylaxis with posaconazole. 75.5% of the 90 patients received posaconazole prophylaxis. All but eight patients received the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan measured twice weekly. Contradicting our guidelines, 89.70% of patients received concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis discontinued and started empirical antifungal treatment in the absence of diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven, probable and possible) with 7.35% of infections being classified as proven or probable. Although limited by a small sample size, our study demonstrates the feasibility of local guidelines in a real life setting and outlines areas for improvement in both guidelines and clinical practice. We also highlight the importance of ensuring awareness of guidelines and raise questions about a uniform approach to antifungal prophylaxis in AML patients.

Topics: Adult; Aged; Antifungal Agents; Female; Fluconazole; Galactose; Guideline Adherence; Guidelines as Topic; Humans; Leukemia, Myeloid, Acute; Male; Mannans; Middle Aged; Mycoses; Pre-Exposure Prophylaxis; Retrospective Studies; Triazoles

Topics: Adolescent; Adult; Aged; Antifungal Agents; Female; Fungi; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Mycoses; Prospective Studies; Triazoles

Invasive fungal disease (IFD) is difficult to diagnose. We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Patients (N = 203) undergoing intensive therapy with expected neutropenia ≥10 d were recruited prospectively and followed for a median (range) of 556 (12-730) d. Baseline chest computerized tomography (CT) was performed pre-therapy. Twice-weekly surveillance with galactomannan (GM) was combined with targeted β-d-glucan (BDG) testing on patients with possible IFD or who were GM-positive. Tissue diagnosis was obtained whenever possible. The cumulative incidence of proven/probable IFD among the 202 evaluable cases after 2 years follow-up was 21%, including 14 proven and 30 probable IFDs. Using either GM or BDG as the sole biomarker (plus host and clinical evidence) the apparent overall incidence of proven/probable IFD was 11% and 16%, respectively. Combined GM/BDG detected all biopsy-proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. Baseline CT abnormalities and Karnofsky score <90, monocytopenia >10 d and bacteraemia were independent risk factors associated with greater than twofold increased IFD risk. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort.

Topics: Adult; Aged; Biopsy; Female; Galactose; Glucans; Hematologic Diseases; Humans; Male; Mannans; Middle Aged; Mycoses; Risk Factors; Tomography, X-Ray Computed; Young Adult

Fungal peritonitis is an uncommon but serious complication of peritoneal dialysis (PD) due to the fact that routine culture to recovered the etiologic agents are time consuming and KOH staining has very low sensitivity. Peritoneal (1→3)-β-D-glucan (BG) or galactomannan (GM), both fungal cell wall components, are candidate biomarkers of fungal peritonitis. Hence, a comparative cross-sectional analysis of peritoneal dialysis fluid (PDF) BG (Fungitell, Cape Cod, MA, USA) and GM (Platelia Aspergillus Ag kits, Bio-rad, France) from all PD patients with and without fungal peritonitis (13 cases, identified by culture), over a 1 year period, was performed. PDF of the fungal peritonitis group showed very high BG (494 ± 19 pg/ml) and high GM (3.41 ± 1.24) similar results were noted in specimens from cases of peritonitis with other causes, especially gram negative bacterial peritonitis. A BG cut-off value at 240 pg/ml and GM at 0.5 showed sensitivity/ specificity at 100%/ 83% and 77%/ 58%, respectively. A concomitantly positive GM reduced the false positive rate of BG from nonfungal peritonitis. In conclusion, BG and GM in peritoneal fluid with provisional cut-off values were applicable as surrogate biomarkers for the diagnosis of fungal peritonitis in PD patients.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Cross-Sectional Studies; Dialysis Solutions; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Peritoneal Dialysis; Peritonitis; Pilot Projects; Proteoglycans; Sensitivity and Specificity

To investigate the clinical characteristics, diagnosis, treatment and prognosis of penicilliosis among the patients with acquired immunodeficiency syndrome (AIDS) in non-endemic areas of China, and then to discuss its incubation period and the diagnostic performance of serum galactomannan test for penicilliosis.. Medical records and travel histories of penicilliosis patients in Zhongnan hospital from January 2006 to December 2013, and the interval from when the patients left the endemic area to the onset of the disease was analyzed. Serum galactomannan levels of penicilliosis patients and AIDS patients with fever were measured by the Platelia Aspergillus Enzyme Immunoassay Kit.. A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. The sensitivity and specificity of serum galactomannan test for penicilliosis were 95.8% (23/24) and 90.9% (30/33), respectively, (cutoff index = 1.0). Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Among 14 patients who became ill after leaving endemic areas, ten patients presented with the onset symptoms within 12 months (from 11 days to 360 days). We found a patient living with asymptomatic P. marneffei fungemia who had not received any antifungal therapy until 18 months' follow up.. The co-infection of P. marneffei and HIV was not uncommon in the non-endemic areas of penicilliosis in China. There exists a latent form of infection for P. marneffei. The incubation period of penicilliosis may be quite different from one patient to another. In AIDS patients, the serum galactomannan test has utility for the diagnosis of penicilliosis. When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; China; Coinfection; Female; Galactose; HIV; Humans; Male; Mannans; Mycoses; Penicillium; Prevalence; Young Adult

Fungal endocarditis (FE) is an uncommon disease with a high risk of morbidity and mortality. Here, we evaluated the different methods for diagnosing this infection. Cardiac valve, vegetation, and embolic materials obtained during surgery were examined for fungal infections by direct smear and culture. At least two blood samples were inoculated at the bedside into BACTEC medium. Galactomannan, mannan Ag enzyme-linked immunosorbent assay, and real-time polymerase chain reaction (PCR) assay were performed with serum samples. Of 25 patients with suspected infective endocarditis (IE), 8 were found to have proven FE according to the direct culture results. The etiologic agents were Aspergillus niger (three cases), A. flavus (two cases), A. fumigatus (one case), and Candida albicans (two cases). Blood culture was positive in only 1 case. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of the results from the galactomannan test were 83.3%, 84.2%, 62.5%, 94.1%, 5.3, and 0.2; these same values, obtained from real-time PCR, were 87.5%, 94.4%, 87.5%, 94.4%, 15.6, and 0.14, respectively. Because mannan antigen was positive in samples from only one patient, we opted not to calculate the sensitivity. However, the specificity value in 23 cases without IE caused by Candida spp. was 100%. Based on our results, both the galactomannan test and real-time PCR can serve as reliable, noninvasive tests for the diagnosis of FE, compared with culture, which is considered to be the gold standard.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Child, Preschool; Endocarditis; Female; Galactose; Humans; Immunoenzyme Techniques; Iran; Male; Mannans; Middle Aged; Mycoses; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity; Young Adult

Testing for serum galactomannan (GM) has been established as an important method for diagnosing invasive aspergillosis (IA); however, limited data exist regarding the application of urine GM testing. The objective of this study was to evaluate the performance of GM screening of urine specimens and to compare results with serum GM. The study was performed between July 2012 and March 2013 in adult patients with underlying hematological malignancies who were hospitalized at the Medical University of Graz, Austria. Serum and urine screening samples were collected and tested twice weekly (always on the same day). In total, 242 serum samples and a similar number of urine samples were collected from 75 patients. A total of 21/242 (8.7%) serum samples from 13 patients were GM positive. Sensitivity, specificity, positive predictive value, and negative predictive value using a 0.1 optical density index cutoff for urine samples (compared with same-day serum results) were as follows: 47.6%, 86%, 24.4%, and 94.5%, respectively. In 8/10 patients with probable IA, at least one positive GM result was found with this cutoff. After calculating clinical performance of the urine GM test, we found that sensitivity increased to 71.4% and specificity to 88.2%. Spearman-Rho correlation analysis revealed a significant positive correlation between serum and urine samples (P < 0.001; ρ = 0.252). In conclusion, GM detection in urine might be a promising method for IA screening. However, further studies are needed.

Topics: Adult; Aged; Aged, 80 and over; Austria; Clinical Laboratory Techniques; Female; Galactose; Hematologic Neoplasms; Hospitals, University; Humans; Male; Mannans; Mass Screening; Middle Aged; Mycoses; Predictive Value of Tests; Sensitivity and Specificity; Serum; Urine; Young Adult

Topics: Adult; Ascomycota; Clinical Laboratory Techniques; Early Diagnosis; Galactose; Humans; Male; Mannans; Mycology; Mycoses; Serum

Invasive fungal infections (IFIs) frequently occur and are associated with high morbidity and mortality in patients with hematologic malignancies (HMs) and hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis of IFI in these patients facilitates prompt institution of therapy and leads to improved clinical outcomes. This article reviews widely used methodologies for diagnosing IFIs in patients with HM and HSCT recipients. Advantages and limitations of radiologic studies; microbiologic and histopathologic techniques; fungal biomarker assays, including those for galactomannan antigen and β-(1-3)-D-glucan; and molecular assays that are available to establish an early diagnosis of clinically relevant invasive fungal infections are discussed. Recommendations are provided regarding effective use of these methodologies in clinical practice.

Topics: beta-Glucans; Biomarkers; Diagnostic Imaging; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Mycological Typing Techniques; Mycoses; Proteoglycans

Fungal wound infection is a leading cause of burn wound infections, and diagnosis is often delayed as it conventionally requires culture and histopathology. Fungal screening assays have sped diagnosis of invasive fungal infections in other populations. Few studies have evaluated the performance of fungal screening assays outside of the hematologic malignancy and hematopoietic stem cell transplant populations.. We performed a three year retrospective analysis of all fungal screening assays in burn patients in the ICU between 2008 and 2011. The primary goal was to evaluate the correlation between the two available fungal screening assays, (1→3)-β-d-glucan (BG) and galactomannan (GM) assay, and fungal wound colonization (FWC) and infection (FWI). We also evaluated previously hypothesized causes of false positives and their associations with false positives in the burn population.. We identified 53 patients [median 29% total body surface area burned (TBSA), IQR 17-51] with BG or GM serological tests available, of which 15 had a FWI or FWC. FWC/FWI was associated with higher TBSA (p=0.02). BG and GM correlated with TBSA (BG 0.57, p<0.01; GM 0.35, p=0.02), but neither assay was associated with FWI/FWC or species of fungus involved when FWI/FWC was diagnosed.. Positive BG and GM fungal screening assays are not associated with FWI/FWC, or with species of fungus when FWC/FWI is present. BG false positives are common and associated with higher TBSA burns.

Topics: Adult; Antigens, Fungal; beta-Glucans; Biomarkers; Burns; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Retrospective Studies; Wound Infection

The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Fungal; Female; Fungi; Galactose; Hematologic Neoplasms; Humans; Italy; Male; Mannans; Middle Aged; Mycoses; Registries; Survival Analysis; Treatment Outcome; Young Adult

Topics: Adult; Child; False Negative Reactions; Female; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Mannans; Mycoses; Transplantation, Homologous

Invasive fungal disease (IFD) remains a significant cause of mortality in haematology patients. Management strategies range from empiric therapy to pre-emptive approaches. Prophylaxis with mould-active agents has been evaluated, but the optimal strategy remains unclear. We present here a retrospective analysis of the pre-emptive strategy implemented at our institution. We analysed 348 consecutive neutropenic episodes in 234 patients. The main elements of our pre-emptive strategy included twice-weekly Galactomannan testing and weekly computed tomography (CT) scan. Antifungal prophylaxis usually consisted of fluconazole (400 mg once weekly). Antifungal treatment was started if criteria for IFD (including possible) were fulfilled. Along with the incidence of antifungal treatment and IFD, we also analysed the adherence to the strategy. Adherence was good but suboptimal with 81% of CT scans having been performed at an interval of 10 days or less. Concerning antifungal treatment, in 56 episodes the patient was receiving a mould-active agent as secondary prophylaxis. Antifungal treatment was started during 39% of the remaining episodes. In all, 109 cases of IFD were diagnosed, 51 being probable or proven. Forty-nine patients died before day 100, IFD directly caused or contributed to death in six patients. Two cases of IFD were diagnosed post-mortem and were missed by our pre-emptive strategy. Our pre-emptive strategy is feasible and safe with an acceptable rate of IFD and associated mortality, while avoiding anti-fungal treatment in a significant proportion of patients. The exact role of pre-emptive treatment compared with systematic mould-active prophylaxis can only be determined in a well-designed randomized trial.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Chemoprevention; Female; Galactose; Guideline Adherence; Health Services Research; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Mycoses; Organizational Policy; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Critical Illness; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Prospective Studies; Proteoglycans; ROC Curve; Sepsis

We assessed the performance of galactomannan and (1→3)-β-d-glucan in 29 serum samples from patients with multiple myeloma and Waldenstrom's macroglobulinemia without invasive fungal disease to address issues of false positivity and uninterpretable results previously reported among patients with these conditions. Galactomannan and (1→3)-β-d-glucan assays were not falsely elevated in any patient. (1→3)-β-d-glucan assay results were uninterpretable in 24% of patients. Patients with IgG levels of >2,000 mg/dl had higher odds of uninterpretable (1→3)-β-d-glucan results.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Diagnostic Errors; Female; Galactose; Humans; Male; Mannans; Middle Aged; Multiple Myeloma; Mycoses; Proteoglycans; Serum; Waldenstrom Macroglobulinemia

The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-β-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients.

Topics: Adolescent; Adult; Aged; Alternaria; Antineoplastic Agents; beta-Glucans; Bone Marrow Transplantation; Candida; Child; Child, Preschool; Female; Galactose; Hematologic Neoplasms; Humans; Incidence; Male; Mannans; Middle Aged; Mycoses; Prospective Studies; Proteoglycans; Young Adult

Topics: Antifungal Agents; Antineoplastic Agents; Fever; Fungi; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Mannans; Mycoses; Neutropenia; Polymerase Chain Reaction; Randomized Controlled Trials as Topic; Retrospective Studies; Triazoles

We report a reactive Aspergillus galactomannan enzymatic immunoassay against the serum of a patient with invasive Prototheca zopfii infection. Analysis of the supernatants of suspensions of P. zopfii and other Prototheca isolates revealed positive results as well. These data suggest cross-reactivity with the serum Aspergillus galactomannan assay in invasive protothecosis.

Topics: Aspergillus; Clinical Laboratory Techniques; Cross Reactions; DNA, Fungal; Galactose; Humans; Immunoenzyme Techniques; Male; Mannans; Middle Aged; Molecular Sequence Data; Mycoses; Prototheca; Sensitivity and Specificity; Sequence Analysis, DNA

To evaluate the diagnostic value of serum galactomannan antigen (GM) and (1→3)-β-D-glucan antigen (BG) assay in invasive fungal infections (IFI) in the patients with hematologic malignancies and the role in monitoring therapeutic response.. Fifty one patients with hematological malignancies met the criteria for inclusion: (1) body temperature above 38°C for 48 hours, (2) failure to respond to broad-spectrum antibiotic treatment, or (3) temperature rose again after the responded drop. Blood samples were collected twice at the first week, then once a week in at least four weeks. The double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and colorimetric assay were used for detecting GM and BG. The positive GM test is defined as two consecutive tests at different time GM value > 0.5 or > 0.8 and the positive G test is defined as BG value > 80 pg/ml. The patients were assigned into four groups as proven, probable, possible, and non-fungal infection respectively, and 21 normal volunteers were as controls.. Two hundred and forty serum samples were collected from 51 patients including 2 of proven IFI, 26 probable IFI, 17 possible IFI and 6 non-fungal infection. The true-positive group including the proven and probable groups, and true negative group was the non-fungal infection group. GM tests were positive in 21 of 28 cases in true positive group, and only one of 6 cases in non-fungal infection. The sensitivity, specificity, positive predictive value and negative predictive value were 75%, 83.3%, 95.5% and 41.7%, respectively. G tests were positive in all 28 cases of the true positive group, and 4 in 6 non-fungal infection cases. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 33.3%, 87.5% and 100%, respectively. G test is more sensitive than GM test (P = 0.015), but there was no significant difference in specificity of the two tests (P = 0.242). In 19 of 21 patients with GM test positive, anti-fungal treatment was effective, and GM value gradually decreased to negative, two invalid patients were persistent with GM test positive. After two weeks treatment, the average GM value was significantly lower in the effective group than in the ineffective group (P < 0.05). BG values in the responded patients showed a gradual decline similar to that of GM values, but not to negative. The changes of BG value in ineffective group varied with a trend upward. The changes in BG value had no relation with treatment effectiveness.. Serum GM and BG antigens detection provides strong evidence for early diagnosis of IFI. Combination of GM and G tests can improve the diagnostic specificity and reduce the false positive GM test seems superior to G test for monitoring GM and BG values during treatment.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; beta-Glucans; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Mycoses; Young Adult

β-D-(1,3)-glucan (BG) is a component of the cell walls of many fungal organisms. Our aims were to investigate the feasibility of the BG assay and its contribution to early diagnosis of different types of invasive fungal infections (IFI) commonly diagnosed in a tertiary care centre. The BG serum levels of 28 patients diagnosed with six IFI [13 probable invasive aspergillosis (IA), 2 proven IA, 2 zygomycosis, 3 fusariosis, 3 cryptococcosis, 3 candidaemia and 2 pneumocystosis] were retrospectively evaluated. The kinetic variations in BG serum levels from the 15 patients diagnosed with IA were compared with those of the galactomannan antigen (GM). In 5/15 cases of IA, BG was positive earlier than GM (time lapse from 4 to 30 days), in 8/15 cases, BG was positive at the same time as GM and, in 2/15 cases, BG was positive after GM. For the five other fungal diseases, BG was highly positive at the period of diagnosis except for the two cases of zygomycosis and one of the three cases of fusariosis. This study, which reflects the common activity of a tertiary care centre, confirms that BG detection could be of interest for IFI screening in patients with haematological malignancies.

Topics: Aspergillosis; beta-Glucans; France; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Mannans; Mycoses; Predictive Value of Tests; Proteoglycans; Retrospective Studies; Time Factors

Myceliophthora thermophila is a thermophilic mould widely found in the environment but rarely responsible for human infections. We describe a case of invasive Myceliophthora thermophila infection mimicking invasive aspergillosis in a neutropenic patient with haematological malignancy. Cross-reactivity with Aspergillus galactomannan assay (GM) was demonstrated by repeated positive results and confirmed by cross-reaction between the fungal isolate and the GM assay. The patient was successfully treated with voriconazole. Potential GM cross-reactivity must be considered in future studies including patients categorized as having probable invasive aspergillosis using the GM as the only mycological criterion.

Topics: Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; Base Sequence; Cross Reactions; Diagnosis, Differential; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Molecular Sequence Data; Mycoses; Neutropenia; Pyrimidines; Sensitivity and Specificity; Sordariales; Spores, Fungal; Triazoles; Voriconazole

We determined the in vitro galactomannan reactivity of isolates recovered from 17 patients with invasive phaeohyphomycosis, 4 of whom had positive galactomannan antigenemia. All isolates were nonreactive using the galactomannan immunoassay. Galactomannan antigenemia in patients with phaeohyphomycosis should raise the possibility of concomitant invasive aspergillosis.

Topics: Aged; Child; Female; Fungi; Galactose; Humans; Immunoassay; Male; Mannans; Middle Aged; Mycoses; Neoplasms

To evaluate the performance of the galactomannan enzyme immunoassay (GM test) and (1,3)beta-D-glucan assay (G test) for the diagnosis of invasive fungal infection (IFI).. A retrospective study was performed in 115 hospitalized patients at Peking University First Hospital who were at risk of IFI. Patients were diagnosed as IFI according to revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at different cutoff values for two assays respectively. Two tests were combined to evaluate the changes of sensitivity, specificity, PPV and NPV.. The best sensitivity (54.5%, 63.6%) and specificity (77.9%, 69.2%) were obtained with the cutoff values of 0.5 and 20 x 10(3) pg/L in GM test and G test respectively. The PPV were 20.7% and 17.9%, and the NPV were 94.2% and 94.7% respectively. The sensitivity increased to 90.9% and the specificity was 52.9% after a combined utility of two tests.. The GM test and G tests are both useful in diagnosis of IFI with the cutoff values of 0.5 and 20 x 10(3) pg/L. A better sensitivity is acquired if there is a combined utility of two tests.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Child; Female; Galactose; Humans; Immunoenzyme Techniques; Male; Mannans; Middle Aged; Mycoses; Plasma; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Serum; Young Adult

Empiric antifungal treatment has become standard of care in children with cancer and prolonged fever and febrile neutropenia (FN), with the downside that it leads to significant over treatment. We characterized epidemiologic, clinical, and laboratory features of invasive fungal disease (IFD) in children with cancer and FN with the aim to identify risk factors for IFD that can aid in better selecting children who require antifungal treatment.. In a prospective, multicenter study, children admitted with FN at high-risk for sepsis, in 6 hospitals in Santiago, Chile were monitored from admission until the end of the FN episode. Monitoring included periodic evaluation of clinical findings, absolute neutrophil count, absolute monocyte count (AMC), serum C-reactive protein (CRP), bacterial cultures, imaging studies, and galactomannan antigen. A diagnosis of proven, probable, and possible IFD was made after episode resolution based on European Organization for Research and Treatment of Cancer classification.. A total of 646 high-risk FN episodes were admitted during the study period, of which 604 were enrolled. IFD was diagnosed in 35 episodes (5.8%) of which 7 (1.2%) were proven, 10 (1.6%) probable, and 18 (3.0%) possible. Four variables obtained on day 4 were significantly more common in IFD cases, which were presence of fever, absolute neutrophil count < or =500/mm, AMC < or =100/mm, and CRP > or =90 mg/L. The combination of fever, AMC < or =100/mm, and CRP > or =90 at day 4 provided a RR for IFD of 5.4 (99% CI, 3.2-9.2) with a sensitivity of 75%, specificity of 87%, positive and negative predictive values of 13% and 99%, respectively.. Fever persisting at day 4 of admission, together with AMC < or =100 and CRP > or =90 significantly increased the risk for IFD in children with cancer.

Topics: Adolescent; Bacteria; C-Reactive Protein; Child; Child, Preschool; Chile; Female; Fever of Unknown Origin; Galactose; Humans; Immunocompromised Host; Infant; Leukocyte Count; Male; Mannans; Mycoses; Neoplasms; Neutropenia; Retrospective Studies; Risk Factors

To evaluate the value of plasma 1, 3-β-D-glucan (G), serum mannan, galactomannan (GM) and cryptococcus capsular antigen assays for diagnosis of invasive fungal infections (IFI) in non-neutropenic adult patients.. This was a prospective case control study. Plasma and serum samples from 25 patients with IFI (candidiasis, aspergillosis, cryptococcosis, zygomycosis, pneumocystis carinii pneumonia), 27 patients with bacterial infections, and 25 healthy adults were collected from February 2007 to February 2009 in Beijing Hospital. The serum antigenic assays were performed and their sensitivity and specificity were analyzed. Optimal cut-off level of G test and mannan was established with receiver operating characteristic curve (ROC).. The concentration of G test in plasma of patients with IFI [89.4 (25.8, 336.9) ng/L] was significantly higher than that of patients with bacterial infection [8.1 (5.0, 34.9) ng/L, U = 120.5, P < 0.001] and healthy adults [3.8 (3.8, 26.0) ng/L, U = 76.5, P < 0.001]. The area under curve (AUC) was 0.858, and the optimal cut-off value was 71.7 ng/L. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 65.0% (13/20), 92.3% (48/52), 76.5% (13/17) and 87.2% (48/55) respectively. The concentration of mannan in serum from patients with candidiasis [1.13 (0.44, 1.22) µg/L] was significantly higher than that from patients with non-candidiasis IFI [0.21 (0.14, 0.27) µg/L, U = 19, P < 0.05], bacterial infection [0.26 (0.22, 0.32) µg/L, U = 36.5, P < 0.001] and healthy adults [0.25 (0.22, 0.30) µg/L, U = 29.5, P < 0.001]. The AUC was 0.894, and the optimal cut-off value was 0.41 µg/L. The sensitivity, specificity, PPV and NPV were 83.3% (10/12), 90.4% (47/52), 66.7% (10/15) and 96.0% (47/49) respectively. The sensitivity, specificity, PPV and NPV of GM antigen to diagnose aspergillosis were 25.0% (1/4), 96.1% (50/52), 33.3% (1/3) and 92.6% (50/54) respectively. The sensitivity, specificity, PPV and NPV of cryptococcus capsular antigen to diagnose cryptococcosis were all 100%.. 1,3-β-D-glucan, mannan and cryptococcus capsular antigen were useful for diagnosis of IFI in non-neutropenic adult patients. GM antigen did not show a good sensitivity for diagnosis of aspergillosis in non-neutropenic adult patients.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; Bacterial Infections; beta-Glucans; Case-Control Studies; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Predictive Value of Tests; Prospective Studies; Proteoglycans; Sensitivity and Specificity

Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in hematologic malignancy patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Child; Female; Galactose; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Male; Mannans; Middle Aged; Mycoses; Proteoglycans; Sensitivity and Specificity

1,3-beta-D glucan (BG) -- the antigen of fungal cell wall can be detected by a commercially available test for early detection of invasive fungal infections (IFI). The main advantage of this test is its broad coverage of fungal species. The aim of our study was to evaluate usefulness of BG detection for screening of IFI and for confirmation of galactomannan (GM) positive blood samples. Combination of the results of both tests could lead to correct and early diagnosis of invasive aspergillosis (IA).. Between January 2005 and July 2007 blood samples were collected in patients from intermediate to high risk of IFI. Moreover, between February and October 2007 all patients that had consecutive positive results of GM had their positive symplex tested also for BG.. In BG screening study, 1154 of blood samples from 104 treatment cycles were tested for BG. The incidence of IFI was 17.3 % (n = 18) and probable or proven IFI was detected in 9 cases (8.6%). The highest sensitivity, specificity, PPV and NPV (88.9 %, 40.7 %, 13.6 % and 97.2 %) were obtained when as criteria for positivity cut off 80 pg/ml and one positive result were used. When consecutive positivity of the test was applied as criterium, cut off 60 pg/ml was found more useful (sensitivity 66.7 %, specificity 47.7 %, PPV 11.8 % and NPV 93.2 %). Low PPV, caused by frequent false positive results, was identified as main limitation of this assay. 65 treatment cycles were positive if 1 sample above 80 pg/ml was used as a cut of for positivity. If consecutive positivity with cut off 60 pg/ml was used, 58 treatment cycles were positive. But in 51 (78.4 %) and 45 (77.5 %) cases, respectively, the positivity was not associated with IFI (false positivity). We did not find any correlation between positive BG assay result and frequency of empirical antifungal treatment, mucositis, yeast colonization, administration of selected antibiotics or infusion solutions or bacteriaemia. In our confirmation study, 40 GM positive episodes in 39 patients were identified. In 31 (78 %) GM positivity was false and was not associated with clinical signs and symptoms of IA. Sensitivity of GM detection in IA was 100 % but PPV only 18 %. Confirmation of consecutive GM positive samples (using cut off index positivity 0,5) by consecutive positivity of BG (with cut off 60 pg/ml) was found very useful for diagnosis of IA -- most of GM false positive results were eliminated and PPV increased to 88 %.. Our analysis focused on routine use of BG test for panfungal screening of IFI in patients with hematological malignancy and confirmed limited usefulness of this test in such setting. Low sensitivity together with low PPV are major limits of this test. On the other hand, BG testing seems to be a promising tool for confirmation of consecutive GM positive result in serum in patients with IA. Positivity of both tests could increase their PPV of tests and eliminate false positive results.

Topics: Antigens, Fungal; beta-Glucans; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Mycoses; Opportunistic Infections; Predictive Value of Tests; Proteoglycans; Sensitivity and Specificity

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Fungal; Aspergillus; Child; Child, Preschool; Cross Reactions; Cryptococcus; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Trichosporon; Young Adult

Invasive mycoses represent a rare but severe complication following hemopoietic SCT (HSCT) in children. Their incidence is related to the type of donor, being higher after allogeneic transplant, especially from alternative donors. Moreover, the incidence of invasive mycoses varies in the different post transplant phases. Neutropenia, lymphopenia, GvHD, high-dose steroids or other immunosuppressive drugs represent well-known risk factors. The clinical features of invasive mycoses after HSCT in children are similar to those observed in adults, and the diagnostic tools, including Aspergillus galactomannan antigen detection, are feasible also in pediatrics. Mortality due to invasive mycoses after HSCT in children is high.

Topics: Aspergillosis; Child; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Mycoses; Risk Factors

Invasive fungal infection (IFI) is a leading cause of infection-related mortality among patients with cancer and prolonged neutropenia and among allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Invasive candidiasis was the principal IFI in the period predating fluconazole prophylaxis, whereas today, invasive aspergillosis and other mold infections cause the majority of deaths from fungal infection in this patient population. The changing epidemiology of IFI, in addition to advances made in antifungal therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier strategies aimed at prevention and early treatment of IFI that were developed several years ago. Here, we propose that persistent neutropenic fever is nonspecific for an IFI and should not be used as the sole criterion for empirical modification in the antifungal regimen in a patient receiving mold-active prophylaxis. We explore the potential benefits and gaps in knowledge associated with employing chest CT scans and laboratory markers as diagnostic adjuncts for IFI. Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Evaluation Studies as Topic; Fever; Fungi; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Mycoses; Neoplasms; Neutropenia; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Tomography, X-Ray Computed; Yeasts

Galactomannan (GM) is a heteropolysaccharide in the cell walls of most Aspergillus and Penicillium species. Cross-reactivity of Cryptococcus neoformans galactoxylomannan in an Aspergillus GM test has also been reported. In this study, we used a Platelia Aspergillus enzyme immunoassay kit (Bio-Rad) to test serum samples obtained from 48 human immunodeficiency virus (HIV)-infected patients (15 with penicilliosis [7 with fungemia alone, 4 with cavitary lung lesions alone, 3 with both fungemia and cavitary lung lesions, and 1 with disseminated disease], 22 with cryptococcosis [11 with fungemia alone, 5 with cavitary lung lesions, 3 with both, and 3 with meningitis alone], and 11 without any invasive fungal infection [control]) for GM levels. None of the patients had aspergillosis or concurrent use of piperacillin-tazobactam or amoxicillin-clavulanate. The median time between diagnosis of fungal infection and collection of serum samples was 0 days for penicilliosis and 1.5 days for cryptococcosis. Of patients with penicilliosis, cryptococcosis, and controls, 73.3%, 13.6%, and 9%, respectively, had GM optical density (OD) indices of >0.5 (P = 0.0001). GM OD indices were higher for penicilliosis (median OD index, 4.419; range, 0.158 to >20) than for cryptococcosis (median, 0.247; range, 0.112 to 3.849) cases (P < 0.001). Patients with fungemic penicilliosis had higher OD indices (median, 10.628; range, 0.401 to >20) than patients with nonfungemic penicilliosis (median, 0.378; range, 0.158 to 4.419) and patients with cryptococcemia (median, 0.231; range, 0.112 to 1.168) (P < 0.001). Of the 15 patients with cavitary lung lesions, those with penicilliosis had higher antigen levels (median OD index, 1.641; range, 0.247 to >20) than those with cryptococcosis (median, 0.227; range, 0.112 to 3.849) (P = 0.011). This study showed that the GM OD index was significantly elevated for HIV patients with penicilliosis. The use of the GM antigen assay may facilitate earlier diagnosis of Penicillium marneffei infection for HIV-infected patients in areas of endemicity.

Topics: Adult; Aged; Aged, 80 and over; Cryptococcosis; Cryptococcus; Female; Fungemia; Galactose; HIV Infections; Humans; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Mycoses; Penicillium; Serum

The Aspergillus galactomannan enzyme-linked immunosorbant assay (EIA) has been demonstrated to facilitate rapid and sensitive detection of invasive aspergillosis. However, test specificity has not been fully evaluated in non-Aspergillus fungal species. Of 53 fungal isolates, cross-reactivity was observed with 5 non-Aspergillus spp.: Blastomyces dermatitidis, Nigrospora oryzae, Paecilomyces lilacinus, Penicillium chrysogenum, and Trichothecium roseum.

Topics: Aspergillosis; Aspergillus; Cross Reactions; Galactose; Humans; Immunoenzyme Techniques; Mannans; Mycological Typing Techniques; Mycoses; Sensitivity and Specificity

Topics: Adult; Antigens, Fungal; Aspergillosis; Galactose; HIV Infections; Humans; Male; Mannans; Middle Aged; Mycoses; Penicillium

Topics: Adult; Biomarkers; Galactose; Hematologic Neoplasms; Humans; Incidence; Mannans; Mycoses; Prospective Studies; Risk; Sensitivity and Specificity

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infection. As the early diagnosis of invasive fungal infection (IFI) is difficult, these infections are still associated with high morbidity and mortality. Recently, Pan-fungal polymerase chain reaction (PCR) has been a promising aid in rapid, early diagnosis of IFI. During the past few years, increasing numbers of suspected IFIs were encountered at our institution in patients with prolonged neutropenia after intensified immunosuppressive chemotherapy. The aim of this study was to investigate the diagnostic utility of both the aspergillus galactomannan (GM) antigen and the pan-fungal PCR assay in the diagnosis of IFI in high risk febrile neutropenic paediatric cancer patients. During one year period, 91 febrile neutropenic (FN) paediatric cases at high risk for developing IFI while receiving chemotherapy were investigated at National Cancer Institute, Egypt. These patients were subjected to clinical evaluation, chest CT scan, conventional blood cultures for bacterial and fungal pathogens, aspergillus GM antigen detection and PCR assay utilizing pan-fungal primers. Of the 91 FN episodes, 15 were proven IFI; whereas 27 cases were either probable (n=13) or possible IFI (n=14), and 49 were unlikely to be IFI episodes. Based on positive results for proven/probable IFI and compared to culture results, Pan-fungal PCR showed sensitivity, specificity, positive and negative predictive values of 75%, 92%, 84% and 87%; respectively. Aspergillus antigen test showed a sensitivity of 79%, specificity of 61%, positive and negative predictive values of 54% and 83%; respectively. A negative PCR in the proven and probable cases was closely related to previous antifungal therapy for a prior history of IFI. In patients at high risk for IFI, neither the sensitivity, nor specificity of the GM test was sufficient. The results of PCR assay was reasonably specific but not very sensitive and had a chance of missing the diagnosis of IFI. The PCR assay seems a promising test for objectively defining IFI, but is not recommended as the only tool for diagnosing IFI. Combining microscopy, culture, and PCR may improve the diagnostic outcome.

Topics: Adolescent; Antigens, Fungal; Aspergillosis; Aspergillus; Blood; Child; Child, Preschool; Egypt; Electrophoresis, Agar Gel; Galactose; Humans; Mannans; Mycoses; Neoplasms; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity; Statistics as Topic

Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a "preemptive" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy.. A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B.. Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis).. Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.

Topics: Adolescent; Adult; Aged; Algorithms; Amphotericin B; Antifungal Agents; Aspergillosis; Feasibility Studies; Female; Galactose; Humans; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Mycoses; Neutropenia; Prospective Studies; Risk Factors; Tomography, X-Ray Computed

Topics: Antigens; Galactose; Humans; Mannans; Mycoses

To improve the immunohistopathological diagnosis of systemic bovine mycoses, we have evaluated the utility of antifungal polyclonal and monoclonal antibodies, and peroxidase and alkaline phosphatase staining techniques. A rabbit polyclonal antibody to mannan from Candida albicans was specific for candidosis. The diagnosis of aspergillosis was accomplished using a rat monoclonal antibody to the galactofuran side chains of Aspergillus galactomannan. A murine monoclonal antibody reacting with weakly Con-A binding 41 and 46 kDa somatic antigens from Absidia corymbifera was used for immunostaining of zygomycetic hyphae. Peroxidase antiperoxidase (PAP) and alkaline phosphatase antialkaline phosphatase (APAAP) complexes were visualized using aminoethylcarbazole and fast red substrates. A green staining of PAP reactions with dioctyl sulfosuccinate sodium and 3,3',5,5'-tetramethylbenzidine (DONS/TMB) was effective for the demonstration of fungi in dual and triple infections. Tissue sections of experimentally infected mice were used to determine the sensitivity and specificity of the antibodies. Tissues obtained from 161 bovine mycotic lesions previously studied by indirect immunofluorescence staining were further evaluated using the three antibodies. In all of 45 lesions solely affected by aspergillosis and in three solely affected by candidosis the diagnoses were confirmed by the new evaluation. In 85 of 96 cases of single infections with zygomycetes the diagnosis was confirmed, while none of the antibodies reacted with fungal elements in the remaining 11 lesions. Aspergillus hyphae were detected in all three lesions with dual aspergillosis and zygomycosis, whereas zygomycetic material was confirmed in only two of these cases. A mixed infection of candidosis and zygomycosis in a lymph node was confirmed too. In 13 cases in which a diagnosis had not hitherto been obtained, aspergillosis and zygomycosis were recorded each in three cases.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Antigens, Fungal; Aspergillosis; Aspergillus; Candidiasis; Cattle; Cattle Diseases; Female; Galactose; Immunoenzyme Techniques; Mannans; Mice; Mice, Inbred BALB C; Mycoses; Omasum; Placenta; Pregnancy; Rabbits