galactomannan and Hematologic-Neoplasms

Invasive mould infections (IMIs), such as invasive aspergillosis or mucormycosis, are a major cause of death in patients with haematological cancer and in patients receiving long-term immunosuppressive therapy. Early diagnosis and prompt initiation of antifungal therapy are crucial steps in the management of patients with IMI. The diagnosis of IMI remains a major challenge, with an increased spectrum of fungal pathogens and a diversity of clinical and radiological presentations within the expanding spectrum of immunocompromised hosts. Diagnosis is difficult to establish and is expressed on a scale of probability (proven, probable and possible). Imaging (CT scan), microbiological tools (direct examination, culture, PCR, fungal biomarkers) and histopathology are the pillars of the diagnostic work-up of IMI. None of the currently available diagnostic tests provides sufficient sensitivity and specificity alone, so the optimal approach relies on a combination of multiple diagnostic strategies, including imaging, fungal biomarkers (galactomannan and 1,3-β-d-glucan) and molecular tools. In recent years, the development of PCR for filamentous fungi (primarily Aspergillus or Mucorales) and the progress made in the standardization of fungal PCR technology, may lead to future advances in the field. The appropriate diagnostic approach for IMI should be individualized to each centre, taking into account the local epidemiology of IMI and the availability of diagnostic tests.

Topics: Aspergillosis; Aspergillus fumigatus; beta-Glucans; Early Diagnosis; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Immunosuppression Therapy; Invasive Fungal Infections; Magnetic Resonance Imaging; Mannans; Mucor; Mucormycosis; Organ Transplantation; Polymerase Chain Reaction; Positron Emission Tomography Computed Tomography; Tomography, X-Ray Computed

The clinical utility of bronchoalveolar lavage (BAL) fluid galactomannan (GM) for the early diagnosis of invasive aspergillosis (IA) varies widely across studies mainly due to heterogeneity of the studied populations.. We conducted a systematic review and meta-analysis of 16 studies involving 783 adults with hematological malignancies to derive summary estimates of the overall accuracy of BAL-GM for diagnosing IA.. Summary estimates of BAL-GM using an optical density (OD) index cutoff value of 1.5 for proven and probable IA were: sensitivity 0.92 (95% CI = 0.48-0.99), specificity 0.98 (95% CI = 0.78-1.00), positive likelihood ratio 53.7 (95% CI = 3.7-771.8), and negative likelihood ratio 0.08 (95% CI = 0.01-0.83). Comparing serum GM and Aspergillus PCR testing on BAL fluid, BAL-GM conferred greater sensitivity, but lower specificity than the serum GM test, and similar specificity as the PCR assay. The use of BAL-GM with serum GM or BAL-PCR tests increased the sensitivity moderately when a positive result was defined by either assay.. GM quantification in BAL fluid at an OD index cutoff value of 1.5 has excellent sensitivity and specificity to assist clinical decision-making in confirming or excluding a diagnosis of IA when results are interpreted with clinical findings. Additional research investigating the effects of antifungal agents, optimal timing and processing of BAL sampling are needed to improve the diagnostic accuracy of BAL-GM testing.

Topics: Adult; Aspergillosis; Bronchoalveolar Lavage Fluid; Galactose; Hematologic Neoplasms; Humans; Mannans; Polymerase Chain Reaction; Sensitivity and Specificity

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

Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy. Issues including primary end-point and patient selection, duration of screening, choice of tests for the pre-emptive strategy, antifungal prophylaxis and bias control, which were considered in the design of the trial, are discussed. We suggest that the template presented herein is considered by researchers when evaluating the utility of new diagnostic tests (ClinicalTrials.gov number, NCT00163722).

Topics: Antifungal Agents; Aspergillosis; Enzyme-Linked Immunosorbent Assay; Galactose; Hematologic Neoplasms; Humans; Mannans; Polymerase Chain Reaction; Randomized Controlled Trials as Topic; Research Design; Risk Factors

A reliable diagnosis of invasive aspergillosis in patients with haematological malignancies is seldom achieved antemortem. Conventional laboratory diagnostic methods are insensitive and time-consuming, resulting in late diagnosis and treatment and contributing to unacceptably high mortality. As a result, routine antifungal prophylaxis and early empirical treatment have been recommended. However, overtreatment associated with these strategies results in increased toxicity and cost. The use of sensitive and rapid non-culture-based diagnostic assays, such as detection of Aspergillus antigens (galactomannan, beta-D-glucan) or detection of genomic DNA sequences may allow a shift in emphasis from empirical to pre-emptive therapy, especially when substantiated by suggestive radiological findings. These new tools may be used to confirm a presumed diagnosis of invasive aspergillosis, or, when used to screen high-risk patients, may identify an infection at the early stage of disease. The excellent negative predictive value of these assays should convince clinicians to withhold antifungal therapy in persistently febrile neutropenic patients with no other signs of fungal infection. On the other hand, consecutive positive results in a high-risk population should at least trigger a complete diagnostic work-up. This review will focus on the diagnostic utility as well as on the pitfalls of serial screening for the presence of circulating fungal antigens in haematology patients.

Topics: Antigens, Fungal; Aspergillosis; Aspergillus; beta-Glucans; Galactose; Hematologic Neoplasms; Humans; Immunoassay; Mannans; Proteoglycans; Serologic Tests

Pulmonary computed tomography (CT) scans are commonly used as part of the clinical criteria in diagnostic workup of invasive fungal diseases like invasive aspergillosis, and may identify radiographic abnormalities, such as halo signs or air-crescent signs. We assessed the diagnostic utility of CT assessment in patients with hematologic malignancies or those who had undergone allogeneic hematopoietic stem cell transplantation in whom invasive aspergillosis was suspected.. This post-hoc analysis assessed data from a prospective, multicenter, international trial of voriconazole (with and without anidulafungin) in patients with suspected invasive aspergillosis (IA; proven, probable, or possible, using 2008 European Organisation for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria) [NCT00531479]. Eligible patients received at least one baseline lung CT scan.. Of 395 patients included in this post-hoc analysis, 240 patients (60.8%) had 'confirmed' proven (9/240, 3.8%) or probable (231/240, 96.3%) invasive aspergillosis (cIA) and 155 patients (39.2%) had 'non-confirmed' invasive aspergillosis (all nIA; all possible IA (de Pauw et al., Clin Infect Dis 46:1813-21, 2008)). Mean age was 52.3 and 50.5 years, 56.3 and 60.0% of patients were male, and most patients were white (71.7 and 71.0%) in the cIA and nIA populations, respectively. Median baseline galactomannan was 1.4 (cIA) and 0.2 (nIA), mean Karnofsky score was 65.3 (cIA) and 66.8 (nIA), and mean baseline platelet count was 48.0 (cIA) and 314.1 (nIA). Pulmonary nodules (46.8% of all patients), bilateral lung lesions (37.5%), unilateral lung lesions (28.4%), and consolidation (24.8%) were the most common radiographic abnormalities. Ground-glass attenuation (cIA: 24.2%; nIA: 11.6%; P < 0.01) and pulmonary nodules (cIA: 52.5%; nIA: 38.1%; P < 0.01) were associated with cIA. Other chest CT scan abnormalities (including halo signs and air-crescent signs) at baseline in patients with hematologic malignancy or hematopoietic stem cell transplantation, and suspected IA, were not associated with cIA.. These findings highlight the limitations in the sensitivity of chest CT scans for the diagnosis of IA, and reinforce the importance of incorporating other available clinical data to guide management decisions on individual patients, including whether empirical treatment is reasonable, pending full evaluation.. NCT00531479 (First posted on ClinicalTrials.gov on September 18, 2007).

Topics: Adult; Anidulafungin; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Invasive Pulmonary Aspergillosis; Karnofsky Performance Status; Lung; Male; Mannans; Middle Aged; Platelet Count; Prospective Studies; Tomography, X-Ray Computed; Voriconazole

Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy.. To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA.. Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479).. 93 international sites.. 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed.. The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures.. Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2 percentage points [95% CI, -19.0 to 1.5]; P  = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different.. Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability.. Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority.. Pfizer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; Aspergillosis; Double-Blind Method; Drug Therapy, Combination; Echinocandins; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Karnofsky Performance Status; Male; Mannans; Middle Aged; Platelet Count; Treatment Outcome; Voriconazole; Young Adult

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

Topics: 14-alpha Demethylase Inhibitors; Adolescent; Adult; Aged; Antifungal Agents; Aspergillosis; Candidiasis; Coccidioidomycosis; Febrile Neutropenia; Female; Galactose; Hematologic Neoplasms; Humans; Itraconazole; Male; Mannans; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult

An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Biomarkers; Female; Fungal Polysaccharides; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Pyrimidines; Survival Analysis; Treatment Outcome; Triazoles; Voriconazole

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

Diagnosing invasive pulmonary aspergillosis (IPA) remains a challenge in patients with hematological malignancies. The clinical significance of testing bronchoalveolar lavage (BAL) samples both with polymerase chain reaction (PCR) and Aspergillus galactomannan ELISA (GM) is unclear, and the BAL cutoff for GM has not been clearly evaluated yet.. Using a validated nested PCR assay and a GM ELISA, we prospectively examined BAL samples from 87 hematological patients at high risk of IPA. Of 76 (87%) evaluable patients, 29 patients had proven or probable disease.. The receiver operating characteristic (ROC) analysis of GM optical density (OD) cutoff levels yielded a BAL OD of 0.5 to be optimal. We identified 29 probable or proven cases based on this OD. Sensitivity and specificity for BAL GM were 0.79 (95% CI, 0.62-0.9) and 0.96 (95% CI, 0.86-0.99), respectively. For BAL PCR, sensitivity and specificity were 0.59 (95% CI, 0.41-0.75) and 0.87 (95% CI, 0.75-0.94), respectively. Combining BAL GM and PCR for diagnosis showed a sensitivity and specificity rate of 0.55 (95% CI, 0.38-0.72) and 1.0 (95% CI, 0.93-1.0), respectively, if positivity was defined by positive results for both tests. If either positive BAL GM or positive BAL PCR results defined test positivity, the sensitivity was 0.83 (95% CI, 0.65-0.92), and the specificity was 0.83 (95% CI, 0.70-0.91). In terms of optimal sensitivity and specificity, a GM OD cutoff of 0.5 was determined for BAL samples. Positivity for both GM and Aspergillus PCR in BAL makes a pulmonary aspergillosis highly likely.

Topics: Adolescent; Adult; Aged; Aspergillus; Bronchoalveolar Lavage; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Pulmonary Aspergillosis; Sensitivity and Specificity

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

We carried out a prospective study on galactomannan enzyme immuno assay (GEI) (Platelia Aspergillus EIA, Bio-Rad) testing for diagnosis of invasive aspergillosis (IA) in serum and broncho-alveolar lavage (BAL) in 200 patients with hematological malignancies and profound neutropenia. The incidence of proven and probable IA was 6% and 5.5%, respectively. In patients with fever or pneumonia, a single-positive GEI test result (galactomannan index >or= 0.5) had excellent specificity (100%). Sensitivity was relatively low (40%) at onset of fever, but increased to 94.7% after 6 days of fever. In patients with infiltrates in chest X-ray or computed tomography scan (n = 48), GEI testing in BAL had a favorable diagnostic accuracy as compared with GEI testing in serum (sensitivity 100% versus 71%). Our findings indicate that antifungal therapy should be started immediately at onset of fever in neutropenic patients with positive GEI tests. In patients with fever refractory to broad-spectrum antibiotics (>or=6 days of fever), the high diagnostic accuracy makes GEI testing a valuable diagnostic tool and questions the common strategy to carry out antifungal treatment irrespective of diagnostic testing in this situation. Our data also show that GEI testing in BAL can be useful for early diagnosis of IA in patients with hematological malignancies and pulmonary infiltrates.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Aspergillosis; Biomarkers; Bronchoalveolar Lavage Fluid; Early Diagnosis; Female; Fever; Galactose; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Incidence; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Neutropenia; Radiography; Sensitivity and Specificity

We determined the value of galactomannan (GM) detection in computerized tomography (CT)-based broncho-alveolar lavage (BAL) fluid and serum for the diagnosis of invasive pulmonary aspergillosis (IPA) in haemato-oncological patients with neutropenia. CT of the thorax and BAL were performed systematically at predefined clinical indications. GM was determined by sandwich enzyme-linked immunosorbent assay; the clinicians were unaware of the results. Of 160 patients, 17 patients (10.6%) presented with proven, probable or suspected IPA. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GM detection in CT-based BAL fluid were all 100%. For GM detection in serially sampled serum, the sensitivity was 47%, the specificity 93%, the PPV 73% and the NPV 82%. A non-blinded follow-up study was performed to validate these results. In this study, 22 of 198 patients (11.1%) presented with IPA, and the sensitivity, specificity, PPV and NPV of GM detection in CT-based BAL fluid were 85%, 100%, 100% and 88% respectively. None of BAL fluids obtained after antifungal treatment of 3 d or more were positive. These results indicate that, when CT is used systematically and at an early stage, GM detection in CT-based BAL fluid has a high PPV for diagnosing IPA early in untreated patients.

Topics: Adult; Aspergillosis; Biomarkers; Bronchoalveolar Lavage Fluid; Follow-Up Studies; Galactose; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Mannans; Predictive Value of Tests; Prospective Studies; Risk; Sensitivity and Specificity; Tomography, X-Ray Computed

Invasive aspergillosis has become the leading cause of death after allogeneic hematopoietic stem cell transplantation. This is partially due to the lack of a prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by means an ELISA technique in serum has been described. The objective of this study was to validate its usefulness in the allogeneic hematopoietic stem cell transplantation setting.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Enzyme-Linked Immunosorbent Assay; False Negative Reactions; Female; Fungemia; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Transplantation Conditioning; Transplantation, Homologous

Serum galactomannan detection is considered to be a useful test for early diagnosis and follow-up of invasive aspergillosis. From February to September 2002, adult patients hospitalized in our Hematology Unit for receiving intensive chemotherapy and/or hematopoietic stem cell transplant were prospectively studied. We analyzed a total of 760 samples obtained from 100 patients. Eleven patients (11%) having a positive result (OD index >1.5 ng/ml) in two consecutive Platelia Aspergillus tests were considered galactomannan-positive cases. On the other hand, 12 patients (12%) were diagnosed of proven or probable invasive aspergillosis. Sensitivity (66.6%), specificity (95.5%), positive predictive value (72.7%) and negative predictive value (96.7%) were comparable to those of larger series. Galactomannan positivity allowed also to anticipate invasive aspergillosis diagnosis (from two to 17 days before radiographic findings and from two to 15 days before mycological culture). Moreover, kinetics of antigenemia could be useful for assessing therapeutic response. Once accepted galactomannan test as a diagnostic criterium for invasive aspergillosis knowing potential causes of false positive results is of paramount importance.

Topics: Adult; Aged; Antigens, Fungal; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; Biomarkers; Combined Modality Therapy; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Fungemia; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Neutropenia; Prospective Studies; Sinusitis

Invasive aspergillosis (IA) affects mainly patients with hematological malignancies, and early diagnosis is crucial for timely treatment. Most diagnoses are based on clinical and mycological criteria, mostly galactomannan (GM) test in serum or bronchoalveolar fluid, which is performed in case of clinical suspicion or as routine screening in patients at high risk who are not receiving anti-mold prophylaxis, for early detection of IA. The aim of this study was to assess in a real-world setting the efficacy of biweekly serum GM screening for the early detection of IA.. A retrospective cohort that included 80 adult patients treated at the Hematology Department, Hadassah Medical Center, 2016-2020, with a diagnosis of IA. Clinical and laboratory data were collected from patients' medical files and the rate of GM-driven, GM-associated, and non-GM-associated IA was calculated.. There were 58 patients with IA. The rate of GM-driven diagnosis was 6.9%, GM-associated diagnosis was 43.1%, and non-GM-associated diagnosis was 56.9%. The GM test as a screening tool had led to IA diagnosis in only 0.2% of screened serums with a number needed to screen in order to find 1 patient with IA of 490.. Clinical suspicion outweighs GM screening as a tool for early diagnosis of IA. Nevertheless, GM has an important role as a diagnostic tool for IA.

Topics: Adult; Aspergillosis; Early Diagnosis; Hematologic Neoplasms; Humans; Retrospective Studies

A rapid and reliable diagnostic test is needed to reduce mortality through early diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies.. To evaluate the efficacy of serum and bronchoalveolar lavage (BAL) Aspergillus galactomannan lateral flow assay (GM-LFA) in IA diagnosis and determine the correlation of GM-LFA with GM enzyme immunoassay (GM-EIA) in patients with hematological malignancies.. In this prospective multicenter study, we used serum and BAL fluid samples from patients with hematological malignancies and suspected IA and performed GM-LFA and GM-EIA. According to the EORTC/MSGERC criteria, patients were grouped as proven (n = 6), probable (n = 22), possible IA (n = 55), or no IA (n = 88). The performance of serum GM-LFA at 0.5 optical density index (ODI) and area under the curve (AUC) were calculated. Spearman's correlation analysis and kappa statistics were performed to determine the agreement between the tests.. GM-LFA showed an AUC of 0.832 in proven/probable IA (sensitivity [SEN], specificity [SPE], negative predictive value [NPV], and diagnostic accuracy were 75%, 100%, 92.6%, and 93.9%, respectively, at a 0.5 ODI) versus that in no IA. A moderate positive correlation was noted between the GM-LFA and GM-EIA scores (p = 0.01). The observed agreement between the tests at 0.5 ODI was almost perfect (p < 0.001). After excluding patients who received mold-active antifungal prophylaxis or treatment, the SEN, SPE, NPV, and diagnostic accuracy for proven/probable IA were 76.2%, 100%, 93.3%, and 94.5%, respectively.. Serum GM-LFA demonstrated high discriminatory power and good diagnostic performance for IA in patients with hematological malignancies.

Topics: Aspergillosis; Aspergillus; Bronchoalveolar Lavage Fluid; Hematologic Neoplasms; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Mannans; Prospective Studies; Sensitivity and Specificity

This study aims to determine the diagnostic utility of galactomannan enzyme immunoassay (GM EIA) in invasive aspergillosis (IA) in children with hematological malignancy (high risk population) in terms of sensitivity, specificity, negative predictive value (NPV) and positive predictive values (PPV) at various cut offs while validating the revised EORTC/MSG 2019 criteria in order to obtain the best cut-off.. For 100 pediatric patients, serum and respiratory samples were collected. Clinical, mycological workup (potassium-hydroxide mount, fungal culture) and GM EIA was done to classify proven, probable, and possible IA as per EORTC-MSG guidelines,2019. Sensitivity, specificity, PPV and NPV were calculated of GM indices at cut-off 0.5, 0.7 and 1, and validated with revised EORTC -MSG, 2019.. Of 100 patients enrolled, 75 were diagnosed with ALL, 14 with AML, two with Hodgkin's, three had non-Hodgkin lymphoma, and six had undifferentiated leukemia. With routine mycological findings, 51 were classified as probable IA, 11 as possible IA, and 38 as no IA. Aspergillus flavus was the most prevalent on culture (56.9%, 29/51) followed by A. fumigatus (29%, 15/51) A. niger (7.8%, 4/51), A. terreus (3.9%, 2/51) and A. nidulans (2%, 1/51). GM EIA demonstrated sensitivity 82.3%, specificity 97.4%, PPV 98.1%, and NPV 77.1% at cut-off 0.67 when comparing probable/possible IA v/s no IA groups. The GM EIA had the best sensitivity (82.4%), specificity (81.8%), PPV (95.5%), and NPV (50%) at cut off 0.78 when the probable IA group was compared to the possible IA. Seven patients succumbed of whom 5 had GMI ≥ 2.. This study deduces the optimal cut-off for serum GM EIA to be 0.67 obtained by ROC analysis when comparing possible and probable IA versus no IA and reinforces the definition of probable category of EORTC-MSG criteria, 2019. At 0.5 ODI the sensitivity (87.1%) and NPV (80.5%) are high, thus making it the most suitable cut-off for detecting true positive and ruling out IA respectively, in pediatric patients with hematological malignancy. GM EIA when performed adjunctive to clinico-radiological findings can prove to be screening, diagnostic and prognostic test for IA in pediatric hematological malignancy patients.

Topics: Aspergillosis; Child; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Mannans; Sensitivity and Specificity

The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) positivity for invasive aspergillosis (IA) in children. Positive GM results between January 2015 and August 2017 were reviewed retrospectively in children with hematologic malignancies. Single and consecutive positive GM results were evaluated according to the different galactomannan index (GMI) (>0.5, >0.7, >1.0 and >1.5) values. There were 104 positive GM results of 70 patients. IA was identified in 29 patients (41.4%) (2 proven and 27 probable). For a single positive GMI of >0.5, >0.7, >1.0, and >1.5, the numbers were 104, 76, 57, and 32 and the positive predictive values (PPVs) were 39.4%, 43.2%, 47.2%, and 50.0%, respectively. The single GM positivity at different thresholds showed no difference between the IA and non-IA group (P>0.05). For 2 consecutive positive GMI values of >0.5, >0.7, >1.0, and >1.5, the numbers were 34, 20, 13, and 4, and the PPVs were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. In the IA group, positivity was higher at all thresholds (P<0.05). According to our findings, consecutive GM positivity has higher PPVs independently from the cutoff value chosen. In pediatric patients with high risk, consecutive sampling should be preferred.

Topics: Adolescent; Aspergillosis; Aspergillus; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Female; Follow-Up Studies; Galactose; Hematologic Neoplasms; Humans; Infant; Male; Mannans; Prognosis; Retrospective Studies; Tertiary Care Centers; Turkey

Invasive pulmonary aspergillosis (IPA) optimal duration of antifungal treatment is not known. In a joint effort, four international scientific societies/groups performed a survey to capture current practices in European haematology centres regarding management of IPA. We conducted a cross-sectional internet-based questionnaire survey in 2017 to assess practices in sixteen European countries concerning IPA management in haematology patients including tools to evaluate treatment response, duration and discontinuation. The following four groups/societies were involved in the project: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG), Infectious Diseases Working Party-European Society for Blood and Bone Marrow Transplantation (IDWP-EBMT), European Organisation for Research and Treatment-Infectious Disease group (EORTC-IDG) and Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM). A total of 112 physicians from 14/16 countries answered the survey. Galactomannan antigen was available in serum and bronchoalveolar lavage in most centres (106/112 [95%] and 97/112 [87%], respectively), quantitative Aspergillus PCR in 27/112 (24%) centres, β-D-glucan in 24/112 (21%) and positron emission tomography in 50/112 (45%). Treatment duration differed between haematological malignancies, with a median duration of 6 weeks [IQR 3-12] for patients with AML, 11 [4-12] for patients with allogenic stem cell transplantation and GvHD and 6 [3-12] for patients with lymphoproliferative disease. Treatment duration significantly differed according to country. Essential IPA biomarkers are not available in all European countries, and treatment duration is highly variable according to country. It will be important to provide guidelines to help with IPA treatment cessation with algorithms according to biomarker availability.

Topics: Antifungal Agents; Antigens, Fungal; Aspergillus; Biomarkers; Bronchoalveolar Lavage Fluid; Cross-Sectional Studies; Disease Management; Duration of Therapy; Europe; Galactose; Hematologic Neoplasms; Humans; Internationality; Invasive Pulmonary Aspergillosis; Mannans; Positron-Emission Tomography; Surveys and Questionnaires

Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population.. To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN.. Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds.. A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04).. Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

Topics: Antifungal Agents; Aspergillosis; Case-Control Studies; Chemotherapy-Induced Febrile Neutropenia; Child; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Male; Mannans; Neoplasms

The aim of this study is to characterize chest CT findings of neutropenic patients with proven/probable invasive pulmonary aspergillosis (IPA).. Hematological cancer patients admitted to our institution (2007-2017) were retrospectively enrolled if the diagnostic criteria of proven/probable IPA during the neutropenia were met (EORTC/MSG). Galactomannan (GM) was routinely measured in serum and chest CT-scan was routinely performed in case of recurrent/persistent fever. Bronchoscopy was performed in case of chest CT-scan abnormalities. Chest CT-scan and GM dosage were analyzed at the time of IPA suspicion. Chest lesions were classified using a clinical report form by two expert radiologists.. 35 patients were identified. Peribronchial focal lesions were observed in 29 IPA (82.9%) by the first radiologist and in 31 (88.5%) by the second (. Peribronchial focal lesions are a common finding in early-IPA whatever the GM value during neutropenia and our findings reinforce the efficiency of a preemptive approach.. Peribronchial focal lesions, which are classically described in airway invasive aspergillosis, are a common finding in early-IPA in hematological cancer patients with prolonged neutropenia regardless of the GM value, and such peribronchial lesions should reinforce the possibility of IPA.

Topics: Adult; Aged; Biomarkers; Bronchial Diseases; Bronchoscopy; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Neutropenia; Prevalence; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

The incidence of invasive aspergillosis (IA) has dramatically increased during the last decade. This infection is associated with high morbidity and mortality, ranging from 30% to 70%, especially in immunocompromised patients. Delay in diagnosis and treatment is usually associated with high mortality rates. This study was aimed to assess the diagnostic value of Galactomannan EIA (GM) for early diagnosis of aspergillosis in hospitalized patients with underlying conditions. Also, the antifungal drug susceptibility profiles of causative agents were investigated. In this descriptive cross-sectional study, during the period of 18 months starting from September 2017 until February 2019, 22 bronchoalveolar lavage (BAL) and 13 biopsies from infected sinuses were obtained from a total of 150 patients suffering from different types of hematologic malignancies. All the samples were subjected to microscopic examination and fungal culture. Also, serum specimens were obtained from all patients (n = 135). 22 serum and 17 BAL specimens were tested for the GM level. Fungal identified were confirmed through the PCR-sequencing of the β-tubulin gene. The susceptibility to amphotericin B, itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin was evaluated according to the Clinical and Laboratory Standards Institute document M38-A2 (CLSI M38-A2) broth microdilution protocol. The results showed that the incident rate of IA was 23.33% and 35 patients with IA (12 proven cases and 23 probable cases) were diagnosed according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria. The 35 patients with IA in the current study comprised 19 men (54.29%) and 16 women (45.71%) with the median age of 42 years. AML (31.5%) was documented as the most prevalent risk factor among our subjects with IA and Aspergillus flavus (65.7%) was the most prevailing causal agent in this study. Among patients with IA, ague (71%) and cough (60%) were the most common symptoms. In the present study, a sensitivity of 94% and a specificity of 98% was reported for GM ELISA in BAL specimens. Also, a sensitivity of 58% and a specificity of 98% was reported for GM ELISA in serum samples. Among 6 tested antifungal drugs, the lowest minimum inhibitory concentration (MIC) values were observed for posaconazole and ravuconazole which showed the range of 0.008-0.0062 μgml and 0.031-0.125 μgml, respectively. The current study has demonstrated that determining

Topics: Adult; Antifungal Agents; Aspergillosis; Bronchoalveolar Lavage Fluid; Cross-Sectional Studies; Female; Galactose; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Male; Mannans; Organ Transplantation; Pharmaceutical Preparations; Sensitivity and Specificity

The present study aims to evaluate the diagnostic yield of bronchoalveolar lavage (BAL) fluid in patients with hematological malignancies and describe the most common pathogens detected in BAL fluid (BALF.) An analysis of 480 BALF samples was performed in patients with hematological malignancies over a period of 7 years. The results of culture methods, PCR, and immunoenzymatic sandwich microplate assays for Aspergillus galactomannan (GM) in BALF were analyzed. Further, the diagnostic thresholds for Aspergillus GM and Pneumocystis jiroveci were also calculated. Microbiological findings were present in 87% of BALF samples. Possible infectious pathogens were detected in 55% of cases; 32% were classified as colonizing. No significant difference in diagnostic yield or pathogen spectrum was found between non-neutropenic and neutropenic patients. There was one significant difference in BALF findings among intensive care units (ICU) versus non-ICU patients for Aspergillus spp. (22% versus 9%, p = 0.03). The most common pathogens were Aspergillus spp. (n = 86, 33% of BAL with causative pathogens) and Streptococcus pneumoniae (n = 46, 18%); polymicrobial etiology was documented in 20% of cases. A quantitative PCR value of > 1860 cp/mL for Pneumocystis jirovecii was set as a diagnostic threshold for pneumocystis pneumonia. The absorbance index of GM in BALF of 0.5 was set as a diagnostic threshold for aspergillosis. The examination of BAL fluid revealed the presence of pathogen in more than 50% of cases and is, therefore, highly useful in this regard when concerning pulmonary infiltrates.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillus; Bronchoalveolar Lavage Fluid; DNA, Fungal; Female; Galactose; Hematologic Neoplasms; Humans; Intensive Care Units; Male; Mannans; Middle Aged; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Streptococcus pneumoniae; Young Adult

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Female; Fungi; Galactose; Hematologic Neoplasms; Humans; Interleukin-6; Interleukin-8; Male; Mannans; Middle Aged; Prospective Studies; Respiratory Tract Infections; ROC Curve

Invasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, but early microbiological diagnosis is difficult. As data on the value of biomarkers in the CNS are scarce, in particular in children, we retrospectively analyzed the performance of galactomannan (GM) and PCR assays in CNS samples of 15 children with proven and probable CNS IMD and of 32 immunocompromised children without fungal infection. Galactomannan in the cerebrospinal fluid (CSF) was assessed in nine of the 15 pediatric patients and was positive in five of them. Polymerase chain reaction (PCR) was performed in eight of the 15 patients and detected nucleic acids from molds in six patients. Galactomannan and PCR in CNS samples were the only positive microbiologic parameter in the CNS in three and two patients, respectively. In four patients, PCR specified the pathogen detected in microscopy. Galactomannan and PCR results remained negative in the CSF of all immunocompromised children without evidence for CNS IMD. Our data suggest that GM and PCR in CNS specimens are valuable additional tools in diagnosing CNS IMD and should be included in the work up of all pediatric patients with suspected mold disease of the CNS.

Topics: Adolescent; Central Nervous System Diseases; Child; Child, Preschool; DNA, Fungal; Female; Follow-Up Studies; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Invasive Fungal Infections; Male; Mannans; Polymerase Chain Reaction; Prognosis; Retrospective Studies

Bronchoalveolar lavage galactomannan (BAL-GM) is a mycological criterion for diagnosis of probable invasive aspergillosis (IA) per European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORT-MSG) consensus criteria, but its real-world positive predictive value (PPV) has not been well-studied. Our aim was to estimate the PPV of BAL-GM in a contemporary cohort of patients with positive BAL-GM.. We identified consecutive patients with ≥1 positive BAL-GM value (index ≥ 0.5) at Brigham and Women's Hospital from 11/2009 to 3/2016. We classified patients as having no, possible, probable, or proven IA, excluding BAL-GM as mycological criterion.. We studied 134 patients: 54% had hematologic malignancy (HM), and 10% were solid organ transplant (SOT) recipients. A total of 42% of positive (≥0.5) BAL-GM results were falsely positive (PPV 58%). The number of probable IA cases was increased by 23% using positive BAL-GM as mycologic criterion alone. PPV was higher in patients with HM or SOT (P < 0.001) and with use of higher thresholds for positivity (BAL-GM ≥ 1 vs 1-0.8 vs 0.8-0.5: P = 0.002).. 42% of positive BAL-GM values were falsely positive. We propose a critical reassessment of BAL-GM cutoff values in different patient populations. Accurate noninvasive tests for diagnosis of IA are urgently needed.

Topics: Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Clinical Laboratory Techniques; False Positive Reactions; Female; Galactose; Hematologic Neoplasms; Humans; Mannans; Middle Aged; Organ Transplantation; Predictive Value of Tests; Pulmonary Aspergillosis; Retrospective Studies; Young Adult

Topics: Aspergillosis; Aspergillus; Bronchoalveolar Lavage; Cytokines; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Mannans; Polymerase Chain Reaction

To investigate the value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) as a noninvasive method for early diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies with febrile neutropenia after antifungal drug treatment.. We retrospectively analyzed the data of 376 patients with febrile neutropenia from January 2015 to August 2017. All patients were given broad-spectrum antibiotics and divided into the control group (effective antibiotic treatment, no antifungal drugs given) and the observational group (ineffective antibiotic treatment, antifungal drugs given). The serum GM testing, chest CT, and microbiological examination findings were compared between the two groups.. The false-positive rates of GM testing for IPA in the control and observational groups were 4.04% and 8.65%, respectively, and the false-negative rates in the two groups were 1.10% and 9.62%, respectively. Sixty-five patients in the observational group and 11 in the control group had typical features of CT imaging.. Clinical weekly screening of serum GM and chest CT may be an effective combined approach to the early diagnosis of IPA in patients with febrile neutropenia, even if they have undergone antifungal treatment.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Aspergillus; Early Diagnosis; Febrile Neutropenia; Female; Follow-Up Studies; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Prognosis; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

In recent years, the introduction of new antifungals for the prevention of invasive fungal infections (IFIs) in hemato- oncological patients, particularly extended-spectrum azoles, has led to a change in the diagnostic and therapeutic strategies for established or suspected breakthrough IFI. The aim of the study was to identify the diagnostic and therapeutic strategies used in the management of IFIs in hemato-oncological patients in Spain, and to assess compliance with the recommendations of the consensus documents and clinical practice guidelines.. An online, anonymous, cross-sectional survey was conducted between January and September 2016 involving 137 specialists from third-level hospitals in Spain with Departments of Hematology that regularly deal with IFIs.. Galactomannan test was available to 95.6% of specialists, and was used in 61.7% of the cases for diagnostic confirmation and early treatment. The (1 → 3) β-D-glucan test was only available to 10.2%. A total of 75.3% of the participants estimated the incidence of breakthrough IFI due to filamentous fungus as being 1-10%. In turn, 83.3% of the participants decided a change in antifungal class after failure of prophylaxis, in concordance with the recommendations of the national and international consensus documents.. The present study, the first of its kind conducted in Spain, shows that a high percentage of the medical professionals implicated in the management of hemato-oncological patients at high risk of suffering IFIs follow the recommendations of the national and international consensus documents and guidelines.

Topics: Antifungal Agents; Azoles; Consensus; Cross-Sectional Studies; Fungi; Galactose; Guidelines as Topic; Health Care Surveys; Hematologic Neoplasms; Humans; Incidence; Invasive Fungal Infections; Mannans; Risk Factors; Spain

Diagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23-59) and 69% (95%CI: 55-81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65-94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32-86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.

Topics: Adult; Aged; Aged, 80 and over; Aspergillus fumigatus; Blood Chemical Analysis; Bronchoalveolar Lavage Fluid; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Molecular Diagnostic Techniques; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Time Factors; Young Adult

Bronchoalveolar lavage (BAL) is recommended for diagnosing lung infiltrates (LI) in patients with hematologic malignancy (HM). Prospective data on the impact of BAL on survival are still lacking. We conducted a prospective observational study on patients who performed BAL for LI among 3055 HM patients hospitalized from January to September 2018. The BAL was performed in 145 out of 434 patients who developed LI, at a median time of four days from LI detection. The median age was 60 (1-83). Most patients had an acute myeloid leukemia/myelodisplastic syndrome (81), followed by lymphoma (41), acute lymphoblastic leukemia (27), and other types of HM (36). A putative causal agent was detected in 111 cases (76%), and in 89 cases (61%) the BAL results provided guidance to antimicrobial treatment. We observed a significantly improved outcome of LI at day +30 in patients who could receive a BAL-driven antimicrobial treatment (improvement/resolution rate: 71% vs 55%; P = .04). Moreover, we observed a significantly improved outcome in 120-day overall survival (120d-OS) (78% vs 59%; P = .009) and 120-day attributable mortality (120d-AM) (11% vs 30%; P = 0.003) for patients who could receive a BAL-driven treatment. The multivariate analysis showed that BAL-driven antimicrobial treatment was significantly associated with better 120d-OS and lower 120d-AM. We did not observe any severe adverse events. In conclusion BAL allows detection of a putative agent of LI in about 75% of cases, it is feasible and well tolerated in most cases, demonstrating that a BAL-driven antimicrobial treatment allows improvement of clinical outcome and survival.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Body Fluids; Bronchoalveolar Lavage; Child; Child, Preschool; Female; Galactose; Hematologic Neoplasms; Humans; Infant; Kaplan-Meier Estimate; Lung; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Pneumonia, Bacterial; Pneumonia, Viral; Proportional Hazards Models; Prospective Studies; Young Adult

Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated.. Prospective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter.. A total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680-0.1040; and 0.1130, IQR 0.0940-0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597-0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen.. GM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients.

Topics: Aged; Aspergillus; Breath Tests; Bronchoalveolar Lavage Fluid; Case-Control Studies; Cell Wall; Cross-Sectional Studies; Exhalation; Female; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Lung Transplantation; Male; Mannans; Middle Aged; Prospective Studies

Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak.. Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months.. During a 10-month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%-100%).. In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Asymptomatic Diseases; Cohort Studies; Disease Outbreaks; Echinocandins; Female; Galactose; Heart Transplantation; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Mass Screening; Micafungin; Middle Aged; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Transplant Recipients; Voriconazole

Invasive aspergillosis (IA) is a life-threatening infection affecting haematological cancer patients with chemotherapy-induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi-weekly serum GM screening has been proposed for a pre-emptive therapeutic approach of IA in patients not receiving mold-active prophylaxis. We have analysed all IA cases among patients with haematological malignancies and prolonged chemotherapy-induced neutropenia (>14 days) in our institution over a 10-year period (2007-2017). Serum GM was measured twice weekly and mold-active prophylaxis was not routinely administered. Thirty IA cases were observed and a positive serum GM was the first indicator of IA in 10 (33%) of them, which represents a need of approximately 500 GM tests for the detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases with negative serum GM for establishing the diagnosis of probable/proven IA. A positive serum GM was associated with a worse prognosis (57% 12-week survival vs 100% among serum GM-negative patients, P = .006), irrespective of the timing of GM positivity compared to CT. We concluded that bi-weekly serum GM screening demonstrated limited benefit in this population.

Topics: Adult; Aged; Aspergillus; Bronchoalveolar Lavage Fluid; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Neutropenia; Polymerase Chain Reaction; Prognosis; Retrospective Studies; Sensitivity and Specificity

To investigate the performance of the routine serum galactomannan (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk haematology patients receiving prophylaxis with micafungin.. Retrospective study including all haematological patients who received prophylaxis with micafungin during high-risk IA episodes (neutropenic patients after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome; allogeneic haematopoietic stem-cell transplantation during early neutropenic phase or graft-versus-host disease requiring high prednisone doses) and for whom at least one sGM result was available. Episodes were classified as follows: true-positive (positive GM in the context of IA), false-positive (positive GM result in patients who had no evidence of IA), true-negative (negative GM test results and no IA), or false-negative (negative GM test in the context of IA). Non-evaluable patients were excluded.. Among 146 evaluable episodes, four were true-positive in the context of probable breakthrough IA (incidence of breakthrough IA, 2.7%); 111/146 high-risk episodes (76%) were considered true-negative and 31/146 (21.2%) were considered false-positive. No false-negative episodes were detected. All but one of the false-positive episodes were detected in surveillance GM tests, leading to high-resolution CT scans in eight cases (8/31; 25.8%), all of which were negative. The positive predictive and negative predictive values of sGM for surveillance and diagnostic approaches were 3.2% (1/31) and 100% (110/110) and 75% (3/4) and 100% (1/1), respectively.. Surveillance of asymptomatic patients receiving prophylaxis with micafungin using sGM is unnecessary, because the results are either negative or false-positive. However, sGM remains useful in the diagnosis of breakthrough IA in symptomatic patients during prophylaxis.

Topics: Adult; Antibiotic Prophylaxis; Aspergillosis; Echinocandins; Female; Galactose; Hematologic Neoplasms; Humans; Lipopeptides; Male; Mannans; Micafungin; Retrospective Studies

Topics: Adult; Antifungal Agents; Aspergillosis; Aspergillus; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Tomography, X-Ray Computed

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

Rapid diagnosis and early treatment of invasive aspergillosis is crucial for the management of the patients with haematological malignancy. We evaluated 358 sera from 78 febrile neutropenic episodes in patient with invasive aspergillosis (IA) (one proven, 17 probable, and 60 possible) and 83 episodes in patients with no IA according to the EORTC/MSG criteria. Patient's specimens were tested by Mycassay Aspergillus PCR (first commercial real-time PCR test) and in house real-time PCR to investigate the presence of Aspergillus DNA, and by ELISA for detect the galactomannan (GM) antigen. We systematically investigated the medical background that can be effective on the test results. The hospitalisation period was longer in proven/probable episodes when compared with no IA (P = 0.001) and possible episodes. With regard to duration of neutropenia, the differences between both proven/probable with no IA (P = 0.023) and possible with no IA (P = 0.002) were highly significant. Similarly, the rates of T cell suppressant therapy in group proven/probable and possible episodes were significantly higher than in no IA (P = 0.005). There are significant differences in the performance of GM and PCR-based tests among studies, and standardisation is required. Therefore, it can be useful to determine the effective factors on these tests. The use of larger volume of sera improved the performance of real-time PCR for detection of Aspergillus DNA in high-risk adult patients in the present study. Some host factors such as duration of neutropenia and administration of T cell suppressants related to the development of IA.

Topics: Adult; Aspergillosis; Aspergillus; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Female; Fever; Galactose; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Male; Mannans; Middle Aged; Neutropenia; Real-Time Polymerase Chain Reaction

Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.).

Topics: Aspergillosis; Biomarkers; Creatinine; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Reproducibility of Results; ROC Curve

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in critically ill patients with hematological malignancies. New diagnosis strategies include the noninvasive biomarkers 1,3-beta-D-glucan (BDG) and serum galactomannan (GM).. For early detection of IPA, we compared BDG Fungitell assay with GM Platelia assay.. Twenty-two out of 30 patients (74 %) had elevated BDG levels (mean 306 pg/ml) beyond the cutoff of 80 pg/ml. GM levels were elevated in only 3 patients (10 %) over the ODI cutoff of >0.5. Following the BDG/GM and microbiological findings, 10 (34 %) cases were classified as probable IPA and 12 (40 %) as possible IPA. Eight (26 %) were classified as no IPA. An overall sensitivity of 90 % (95 % CI 86-96 %) and specificity of 85 % (95 % CI 79-86 %) was found for the BDG Fungitell assay in IPA. In contrast, an overall sensitivity of 30 % (95 % CI 26-38 %) and specificity of 98 % (95 % CI 94-100 %) was found for the GM Platelia assay. A false-negative rate of 70 % for probable IPA and 85 % for probable/possible IPA was detected for GM. The false-negative rate for BDG was 0 % in cases of probable IPA and 45 % in cases of possible cases.. BDG is a sensitive marker for patients' surveillance at risk of IPA. In patients with hematological malignancies and septic shock, early diagnosis of IPA might be significantly improved by BDG compared to GM, also considering that BDG has the advantage of detecting fungal diseases other than IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; beta-Glucans; Critical Illness; Diagnostic Tests, Routine; Early Diagnosis; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Proteoglycans; Sensitivity and Specificity; Serum; Shock, Septic; Young Adult

Invasive aspergillosis (IA) is a fatal infection that is difficult to diagnose in immunocompromised patients. In this study, Aspergillus-specific DNA was searched using real-time PCR (RT-PCR) in serum samples. Galactomannan (GM) and/or beta-D-glucan (BDG) tests were previously performed on these samples for 70 neutropenic patients with hematological malignancy.. The patients were categorized according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG). Among the patient serum samples, the first positive GM or BDG test sample and the median sample of GM or BDG test for negative patients were used to detect DNA levels by RT-PCR method (Light Cycler 480, Roche Molecular Biochemicals, Meylan, France) using a commercial kit (Way2Gene Fungi; Genmar, İzmir, Turkey).. When the proven and probable IA group were considered as real patients, sensitivity of Aspergillus-specific DNA test was 90%, specificity was 73.3%, positive predictive value was 81.8%, and negative predictive value was 84.6%.. This study found that searching for specific DNA by RT-PCR method has a sensitivity as high as the GM test. Although specificity was rather low, it was concluded that it can be used jointly with GM and BDG tests after decreasing contamination by severe laboratory applications.

Topics: Adult; Aspergillosis; Aspergillus; DNA; Galactose; Hematologic Neoplasms; Humans; Mannans; Turkey

We evaluated the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) in patients with underlying haematological malignancies. Participating centres were the two Austrian University Hospitals of Graz and Innsbruck. LFD performance was evaluated with 95 bronchoalveolar lavage fluid (BALF) samples from 72 patients collected prospectively in Graz, and with 24 BALF bio bank samples from 23 patients (21 samples with probable IPA) in Innsbruck. Invasive fungal infections were classified according to the revised European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria. Overall, 27 patients (30 samples) had probable IPA, 32 (43 samples) possible and 36 (46 samples) did not fulfil IPA criteria. The vast majority of patients - in particular those with probable IPA - received mould-active treatment before bronchoscopy. Sensitivity, specificity, positive predictive value and negative-predictive-value for probable IPA diagnosis using the BALF-LFD test were 71%, 76%, 35% and 94% for the Graz cohort. Sensitivity of the BALF-LFD test for probable IPA was 57% in Innsbruck bio bank samples. Our results indicate that the BALF-LFD-test provides fast results with moderate sensitivities in patients with underlying haematological malignancies. Similar to other diagnostic tests and biomarkers sensitivity of the test may be influenced by ongoing systemic mould-active treatment.

Topics: Aged; Aspergillus; Austria; Biomarkers; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Female; Galactose; Hematologic Neoplasms; Humans; Immunologic Tests; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Point-of-Care Testing; Prospective Studies; Sensitivity and Specificity

We assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case-control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.. In this observational study 162 biomarker analyses were performed on samples from 27 febrile neutropenic episodes. Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets. Furthermore thoracic computed tomography scanning was performed along with bronchoscopy with lavage when clinically indicated. Patients were retrospectively stratified to define a case-group with "proven" or "probable" invasive pulmonary aspergillosis (25.93 %) and a control-group of patients with no evidence for of invasive pulmonary aspergillosis (74.07 %). In 44.44 % of episodes fever ceased in response to antibiotic treatment (group II). Empirical antifungal therapy was administered for episodes with persistent or relapsing fever (group I). 48.15 % of patients died during the study period. Postmortem histology was pursued in 53.85 % of fatalities.. Concordant negative galactomannan and computed tomography supported by a polymerase chain reaction assay were shown to have the highest discriminatory power to exclude invasive pulmonary aspergillosis. Bronchoalveolar lavage was performed in 6 cases of invasive pulmonary aspergillosis and in 15 controls. Although bronchoalveolar lavage proved negative in 93 % of controls it did not detect IPA in 86 % of the cases. Remarkably post mortem histology convincingly supported the presence of Aspergillus hyphae in lung tissue from a single case which had consecutive positive polymerase chain reaction assay results but was misdiagnosed by both computed tomography and consistently negative galactomannan assay results. For the galactomannan enzyme-immunoassay the diagnostic odds ratio was 15.33 and for the polymerase chain reaction assay it was 28.67. According to Cohen's kappa our in-house polymerase chain reaction method showed a fair agreement with the galactomannan immunoassay. Combined analysis of the results from the Aspergillus galactomannan enzyme immunoassay together with those generated by our polymerase chain reaction assay led to no misdiagnoses in the control group.. The data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Antigens, Fungal; Aspergillus fumigatus; Case-Control Studies; DNA, Fungal; Female; Galactose; Hematologic Neoplasms; Humans; Immunoassay; Invasive Pulmonary Aspergillosis; Lung; Male; Mannans; Middle Aged; Neutropenia; Pilot Projects; Polymerase Chain Reaction; Prospective Studies; Tomography, X-Ray Computed; Young Adult

The combination of two quantitative Aspergillus PCR assays, targeting a mitochondrial and a ribosomal target (AfQPCR), has proved effective for diagnosing invasive aspergillosis (IA) in hematology patients with risk factors and a positive galactomannan antigen (GM). The aim of the present study was to assess the performance of systematic AfQPCR for IA screening in at risk patients in a hematology intensive care unit (ICU). The study was performed in the hematology ICU at Besançon University Hospital from March 2012 to December 2013. GM detection (Platelia Aspergillus, Biorad, France) and AfQPCR were performed on the same serum sample, twice a week, in all patients with risk factors for IA. Risk factors and clinical, radiological, and biological data were prospectively recorded using the information sheet from the French network for the surveillance of Invasive Fungal Infection. Thirty-two patients were diagnosed with proven, probable, or possible IA according to the 2008 EORTC/MSG criteria. Sixteen patients had a positive AfQPCR: 9/16 had a positive GM at the same time (GM index >0.5), 4/16 had a positive GM before the AfQPCR and 3/16 had a negative GM at the time of the positive AfQPCR. Screening at risk patients using both AfQPCR and GM on the same serum sample is very feasible in a routine clinical setting. Our results confirm the usefulness of combining biomarkers for an early IA diagnosis.

Topics: Aspergillus; Early Diagnosis; France; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Mannans; Prospective Studies; Real-Time Polymerase Chain Reaction; Serum

In this study, the sensitivity-specificity of galactomannan-enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated.. IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined.. Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA ≥ 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results.. With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Opportunistic Infections; Predictive Value of Tests; Reproducibility of Results; Time Factors

The diagnosis of invasive pulmonary aspergillosis is challenging. It is unclear whether galactomannan (GM) results from bronchial wash (BW) and bronchoalveolar lavage (BAL) samples differ in a clinically meaningful way.. Ninety-six paired (BAL and BW) samples from 85 patients were included. The average age was 53 years, 61 % of the patients were male, and 74.1 % had an underlying diagnosis of AML/MDS (ALL 7.1 %, other hematologic malignancy 18.8 %). 57 (67.1 %) patients were neutropenic, and 56 (65.9 %) patients were receiving mold-active drugs at least 48 h prior to bronchoscopy. The overall agreement between GM detection from BW and BAL was 63.5 % (K = 0.152; 95 % CI 0.008-0.311) and 73 % (K = 0.149; 95 % CI 0.048-0.348) at cut off ≥0.5 and ≥1.0, respectively. Among 43 positive samples, using a GM cut-off of 0.5, 39 (90.5 %) were positive in BW samples whereas 12 (29.3 %) were positive in BAL samples. The median level of GM in BW (0.28) samples was significantly higher than in BAL (0.20) samples among 53 samples with negative results (P = 0.001). There was no statistically significant difference in the median GM values between the BW and BAL samples with positive results (P = 0.08). There was no significant difference in GM detection between samples with positive and negative results with regard to antifungal, beta lactam antibacterial treatment or neutropenia (60.5 vs 56.6 %; 53.9 vs 46 %; 65.1 vs 54.7 %, respectively).. This retrospective study examining two collection techniques suggests that BW may have higher diagnostic yield compared to bronchoalveolar lavage for GM detection.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Diagnostic Tests, Routine; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Retrospective Studies; Young Adult

Aspergillus infections are major causes of morbidity and mortality among immunocompromised patients. This study was designed to investigate the galactomannan assay optical density (OD) indices relative to the culture results in bronchoscopic samples obtained from neutropenic and non-neutropenic patients. Galactomannan OD indices from 1427 samples from 2005 to 2012, which were sent from 839 patients and were composed of bronchial lavage (BL = 727) and bronchoalveolar lavage fluids (BAL = 700), were retrospectively analysed. The recovery rates of Aspergillus species from these specimens were 9.4% from the combined patient group and 13.3% from the neutropenic group. Aspergillus fumigatus complex was the most frequently isolated species. The mean and median OD indices of the positive and negative culture samples are approximately 5 and 1, respectively, and 91% of all culture-positive samples have ≥1 OD index value. The receiver-operating characteristics curve analysis demonstrated that the feasibility of the Aspergillus galactomannan assay and Aspergillus galactomannan test has superior accuracy in BAL compared to BL fluids, and the test is not affected by the immune status of the patient. We suggest that the Aspergillus galactomannan test, which uses bronchoscopic material, leads to an earlier diagnosis and if the OD index is found ≥1, fungal growth can be expected.

Topics: Aspergillosis; Aspergillus fumigatus; Bronchoalveolar Lavage Fluid; Galactose; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Mannans; Neutropenia; Retrospective Studies; Specimen Handling

Invasive aspergillosis is a leading cause of morbidity and mortality in immunocompromised patients, particularly in individuals with haematological malignancy and in haematopoietic stem cell transplant recipients. Nowadays, the galactomannan (GM) assay has been widely used as an indication of invasive aspergillosis, even though the test is known to generate false-positive results. The aim of this study was to compare the performance of GM and real-time PCR (qPCR) to detected Aspergillus in blood samples obtained from high-risk haematological patients. Haematological patients were screened twice weekly with GM testing, which was performed by the Platelia ELISA kit. An additional sample of whole blood (4 ml) was obtained for the purpose of qPCR testing. Sixty-four samples from 12 patients with haematopoietic stem cell transplant or haematological malignancy were studied. The overall accordance between GM and qPCR tests was 96.9 % (62 samples). Only two samples showed contradictory results, with positive GM test and negative real-time PCR results. Based on the high concordance between GM and qPCR in terms of negative results, the main utility of qPCR could be in the confirmation of positive results seen with GM testing.

Topics: Adult; Aspergillosis; Aspergillus; DNA, Fungal; False Positive Reactions; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Mannans; Mass Screening; Middle Aged; Pilot Projects; Real-Time Polymerase Chain Reaction; Young Adult

This study was undertaken to examine the performance of the Fungitell β-glucan (BG) assay, to compare it with that of the galactomannan (GM) test for the diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies, and to examine the rates of false-positive BG and GM test results due to β-lactam antibiotics among sera of patients with Gram-positive or Gram-negative bacteremia and selected sera with false-positive results from the GM test. Serum samples from 105 patients with proven (n = 14) or probable (n = 91) IA, 97 hematology patients at risk for invasive fungal infections, 50 healthy blood donors, and 60 patients with bacteremia were used to study the sensitivities and specificities of the assays. The GM test was more specific than the BG assay (97% versus 82%, respectively; P = 0.0001) and the BG assay was more sensitive than the GM test (81% versus 49%, respectively; P < 0.0001) for IA diagnosis. The study of 49 separate batches of β-lactam antibiotics showed high and very similar rates of false-positive results for the GM and BG assays (29 and 33%, respectively; P = 0.82) but with an almost complete lack of concordance between the 2 assays. For patients with bacteremia, the rate of false-positive results was much higher with the BG test than with the GM test (37% versus 2%, respectively; P < 0.0001), with no significant difference between Gram-positive and Gram-negative bacteremia. In conclusion, the BG test may be useful for the diagnosis of IA because of its high sensitivity in comparison with the GM test, but the overall benefit of this assay remains limited because of its inadequate specificity and its cost.

Topics: Anti-Bacterial Agents; Antigens, Fungal; beta-Glucans; beta-Lactams; False Positive Reactions; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Mannans; Proteoglycans; Sensitivity and Specificity; Serum

Interpretation of Aspergillus galactomannan (GM) and PCR results in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with haematological malignancies requires clarification. A total of 116 patients underwent BAL for investigation of new lung infiltrates: 40% were neutropenic, 68% and 36% were receiving mould-active antifungal agents and β-lactam antibiotics. The diagnosis of proven IPA (n = 3), probable IPA (n = 15), and possible invasive fungal disease (IFD, n = 50) was made without inclusion of GM results. BAL GM (at cut-off of 0.8) had lower diagnostic sensitivity for IPA than PCR (61% versus 78%) but higher specificity (93% versus 79%). Both tests had excellent negative predictive values (85-90%), supporting their utility in excluding IPA. The use of BAL GM and PCR results increased the certainty of Aspergillus aetiology in 7 probable IPA cases where fungal hyphae were detected in respiratory samples by microscopy, and upgraded 24 patients from possible IFD to probable IPA. Use of BAL GM and PCR improves the diagnosis of IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Fungal; Aspergillus; Bronchoalveolar Lavage Fluid; DNA, Fungal; Galactose; Hematologic Neoplasms; Humans; Immunoassay; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; 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

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in immunocompromised patients.. We hypothesize that galactomannan (GM), a component of fungal cell wall, as measured in bronchoalveolar lavage (BAL) might be a diagnostic adjunct in hematologic malignancies.. A total of 568 hematologic cases undergoing diagnostic bronchoscopy because of respiratory symptoms and/or suspected IFD between 2009 and 2013 at a tertiary care center in Switzerland were included in this prospective, observational cohort study. We compared accuracy of the BAL GM ELISA determination in predicting IFD as classified by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG) definition.. BAL GM was positive in 155 cases (29.2%). According to the EORTC/MSG criteria, IFD was classified as possible in 182 (34.3%), probable in 45 (8.5%), and proved in six (1.1%). BAL GM provided 50% sensitivity, 73.0% specificity, 16% positive predictive value, and 93% negative predictive value for diagnosing proven+probable IFD. Results were similar when antifungal treatment and radiologic suspicion of IFD were used as the gold standard. The area under the curve of the receiver operating characteristic curve for the diagnosis of proven+probable IFD was 0.716 (95% confidence interval, 0.638-0.794; P < 0.001).. GM in BAL had modest agreement with EORTC/MSG criteria for diagnosing IFD in immunocompromised patients with a high degree of antifungal exposure.

Topics: Adult; Antifungal Agents; Area Under Curve; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chemoprevention; Female; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Logistic Models; Male; Mannans; Middle Aged; Prospective Studies; Sensitivity and Specificity; Statistics, Nonparametric; Switzerland

Invasive aspergillosis (IA) is a major problem in the immunocompromised population, and its diagnosis is difficult due to the low sensitivity of available tests. Detection of Aspergillus nucleic acid by polymerase chain reaction (PCR) in serum samples is a promising diagnostic tool; however, use of multiple "in-house" methods precludes standardization. The first commercial PCR assay, MycAssay Aspergillus (Myconostica, Ltd), became available recently, and its performance in the diagnosis of IA was evaluated and compared with the galactomannan (GM) assay. Serum samples obtained from patients with hematological cancer were tested retrospectively with MycAssay Aspergillus PCR. Per-episode and per-test analyses were undertaken with 146 sera from 35 hematological patients. Sixteen patients had proven or probable IA and 19 had possible or no IA. In per-episode analysis, MycAssay Aspergillus had a sensitivity of 43.8% (95% confidence interval [CI], 19.8%-70.1%) and a specificity of 63.2% (95% CI, 38.4%-83.7%) for IA diagnosis. In per-test analyses, MycAssay Aspergillus had a lower specificity than the GM assay (83.3% vs. 93.1%, P = 0.04). The addition of PCR to routine clinical practice would have permitted the diagnosis of one additional probable IA in our cohort. Use of PCR instead of GM assay would have delayed the diagnosis in two cases. Aspergillus DNA detection by PCR with serum specimens using MycAssay showed a lower specificity than the GM assay and was associated with a low sensitivity for IA diagnosis. More studies are needed to determine the exact role of MycAssay in IA diagnosis in patients with hematological malignancy.

Topics: Adult; Aged; Aged, 80 and over; Aspergillus; DNA, Fungal; Female; Galactose; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Serum

Topics: Bronchoalveolar Lavage Fluid; Female; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Male; Mannans

Data on diagnostic performance of Galactomannan (GM) testing in patients under mould-active regimens are limited. Whether sensitivity of GM testing for diagnosing breakthrough invasive aspergillosis (IA) is decreased under antifungal prophylaxis/therapy remains therefore a point of discussion. We retrospectively analysed GM test results in patients who were admitted with underlying haematological malignancies to two Divisions of the Medical University Hospital of Graz, Austria, between 2009 and 2012. Only cases of probable and proven IA that were diagnosed by other methods than GM testing were included (time of diagnosis = day 0). We compared GM results of patients with/without therapy/prophylaxis for the period of 2 weeks prior (week -2) until 3 weeks postdiagnosis. A total of 76 GM test results in nine patients were identified. Six patients had received antifungal therapy/prophylaxis from week -2, whereas three patients were treated with therapy from the time of diagnosis at week 0. GM testing was positive in 45/76 (59%) of samples. Sensitivity of GM testing for detection of proven or probable IA at week -1 and 0 was 77% and 79% in patients with mould-active regimens. We conclude that GM testing might be a useful diagnostic method for breakthrough IA in patients receiving mould-active prophylaxis/therapy.

Topics: Adolescent; Adult; Antifungal Agents; Austria; Chemoprevention; Clinical Laboratory Techniques; Female; Galactose; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Retrospective Studies; Sensitivity and Specificity; Young Adult

Invasive aspergillosis (IA) is a leading complication of intensive treatment for haematological malignancies. Earlier diagnosis should facilitate effective antifungal therapy and prevent progression to invasive disease, which is often lethal. Polymerase chain reaction (PCR) assays, targeting the 28S and ITS ribosomal gene regions respectively, were evaluated for early detection of Aspergillus DNA and for diagnostic utility in patients receiving treatment in two busy haematopoietic stem cell transplant centres. Patients undergoing intensive chemotherapy, autologous or allogeneic transplant were eligible for inclusion in the study. EDTA blood and serum samples for circulating Aspergillus biomarkers, including galactomannan (GM), were collected twice-weekly on a prospective basis from all study patients who were categorized according to international consensus criteria for defining invasive fungal disease (IFD). Of 278 patients recruited there were 44 probable IA cases and only one proven case. Moderate sensitivity and specificity, poor positive predictive value (50-80%), but good negative predictive value (>80-90%) were common to both PCR assays. Overall biomarker performance could be improved by combining positive results of either PCR assay with GM taken within a 12-d period. The addition of PCR to GM monitoring in high-risk patients with haematological malignancies provides greater diagnostic accuracy in invasive aspergillosis.

Topics: Aspergillosis; Aspergillus; DNA, Ribosomal Spacer; Galactose; Hematologic Neoplasms; Humans; Incidence; Mannans; Prevalence; Real-Time Polymerase Chain Reaction; RNA, Ribosomal, 28S; Sensitivity and Specificity; Time Factors; Tomography, X-Ray Computed

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

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised children. We investigated the usefulness of an Aspergillus galactomannan (GM) antigen assay as a diagnostic tool for IA in pediatric cancer patients and hematopoietic cell transplantation (HCT) recipients.. The GM antigen assay results were analyzed in 749 blood samples from 99 patients. A GM index (GMI) greater than or equal to 0.5 on at least two separate occasions was considered positive. A review of the clinical data was performed for subjects with proven or probable IA.. Twenty-one of 23 patients with proven or probable IA had positive GM antigen test results (91.3% sensitivity, 95% CI 71.9-98.9; 81.7% specificity, 95% CI 69.6-90.5; P < 0.0001). The false-positive rate was 18.3%. Being younger than 3 years of age, having a solid tumor, and receiving HCT within 4 weeks of the test were statistically significant factors for causing false-positive results (P < 0.05). Among the 23 patients with IA (six proven, 17 probable), 16 (69.6%) had hematological malignancies, five (22.7%) had solid tumors, and two (8.7%) had primary immunodeficiency. Nineteen patients (82.6%) received HCT. The most common clinical site of IA was the lungs (91.3%), and consolidation was the most frequent finding in chest CT scans (36.8%). The mortality at 12 weeks was 43.5%.. Having a positive GM assay at least twice is useful in diagnosing IA in pediatric patients with cancer and HCT recipients.

Topics: Adolescent; Antigens, Fungal; Aspergillosis; Child; Child, Preschool; False Positive Reactions; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunoenzyme Techniques; Infant; Male; Mannans; Sensitivity and Specificity

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

Diagnostic efficacy of Galactomannan (GM) assay for invasive aspergillosis (IA) is variably reported. Data from developing countries are scant. Children with haematological malignancies and fever were enrolled prospectively. Blood sample for GM was drawn on the day of admission; levels were measured with Platellia Aspergillus enzyme immunoassay. Diagnostic criteria were adapted from EORTC-MSG-2002. Proven, probable and possible episodes were considered as the disease group. One hundred febrile episodes in 78 patients were evaluated. The mean age was 6.1 years. Majority (75%) episodes were in patients with acute lymphoblastic leukaemia. One episode each was diagnosed with proven and probable IA, while 23 were diagnosed with possible IA. Best results were obtained with a cut-off value of 1.0, with sensitivity, specificity, positive and negative predictive value of 60%, 93%, 75 and 87 respectively. The sensitivity dropped to 40%, at cut-off value of 1.5 and specificity was 38%, at a cut-off of 0.5. A higher value of GM correlated with pulmonary nodules (P = 0.037) and mortality (P = 0.001). GM assay is adjunctive to clinical/radiological evidence. A negative GM assay may not reassure the physician against the use of amphotericin in patients with febrile neutropenia, as it does not exclude the diagnosis of clinically relevant other fungal infections, particular mucormycosis.

Topics: Adolescent; Child; Child, Preschool; Female; Fungemia; Galactose; Hematologic Neoplasms; Humans; Infant; Invasive Pulmonary Aspergillosis; Male; Mannans; Predictive Value of Tests; Sensitivity and Specificity; Serum

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

Galactomannan (GM) is a polysaccharide component of the cell wall of Aspergillus spp. and is released into the host's circulation by growing hyphae. GM testing of patients with hematological malignancies has been rarely considered in recent epidemiologic studies of invasive mould infections (IMIs). The aim of the investigation was to analyze the impact of GM testing on the reported prevalence of IMI by comparing detection rates of IMI before and after the introduction of this diagnostic procedure. Prevalence of IMI was assessed by conducting a prospective single-centre study over seven months in 2010. Results obtained were then compared to those obtained with a representative collection of patients assessed by the same investigators at the same institution over seven months in 2007, i.e., prior to the introduction of GM testing. We found that, in general, detection rates of invasive aspergillosis (IA) and invasive mould infections increased significantly after the introduction of GM analysis. This study may therefore indicate that GM testing has a significant impact on the reported prevalence of IMI. Broad usage of such testing in patients with hematological malignancies may be able to produce a realistic picture of IMI rates when current diagnostic criteria are applied.

Topics: Aspergillosis; Aspergillus; Clinical Laboratory Techniques; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Prevalence; Prospective Studies

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in profoundly neutropenic patients. Delayed diagnosis and therapy may lead to poor outcomes.. The objective of this study was to assess the performance characteristics of the galactomannan (GM) assay in serum and bronchoalveolar lavage specimens for the diagnosis of IA in neutropenic patients with hematological malignancies. We also evaluated the prognostic outcome.. A total of 1198 serum samples and 42 BAL from 235 neutropenic patients were tested with a GM elisa platelia test. We used Cox modeling of time to 6- and 12-week mortality for GM level at the time of diagnosis (GM0) and GM decay in the week following diagnosis in proven and probable IA patients with more than two GM values.. There were three proven, 55 probable, and four possible cases of IA. The sensitivity and specificity of the GM test were 96.8% and 82.4% respectively. In BAL samples, sensitivity was 86% and the specificity 93%. BAL GM was more sensitive than microscopy (22.2%) and BAL culture (38.9%). Among patients with proven/probable IA, serum and BAL GM were in agreement for 92.8% of paired samples. The hazard ratio (HR) of GM0 and 1-week GM decay per unit increase in Aspergillus enzyme immunoassay (EIA) was 1.044 (95% CI, 0.738 to 1.476) and 0.709 (95% CI, 0.236 to 2.130) respectively.. We found good correlation between the GM0 and GM decay combination and outcome of IA patients. The GM is a useful tool for diagnosis and monitoring of IA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Bronchoalveolar Lavage Fluid; Child; Cohort Studies; Female; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Infant; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Neutropenia; Prognosis; Sensitivity and Specificity

To describe and estimate the rate of breakthrough invasive mould diseases (IMD) in patients receiving caspofungin.. Retrospective, non-interventional study conducted in three University Hospitals.. Nineteen breakthrough infections have been identified including 13 aspergillosis, 2 mucormycosis, a fusariosis, a Hormographiella aspergillata infection and 2 possible IMD. Cases were equally distributed between the centres. Fourteen patients had a haematologic malignancy, four were transplant recipients (allogeneic haematopoietic stem cells in three, liver in one) and one had hepatic cirrhosis. Caspofungin has been prescribed as prophylaxis (n = 3), empirical therapy (n = 9) or directed therapy for candidemia (n = 5) or aspergillosis (n = 2). Aspergillus galactomannan was positive in serum or in bronchoalveolar lavage fluid in 10 of the 13 aspergillosis. Median duration of caspofungin treatment before breakthrough IMD was 15 days. Nine patients died within twelve weeks. Rate of breakthrough IMD in onco-haematology patients has been estimated to 7.3% for all mould infections and to 4.2% when restricted to documented aspergillosis.. Our data call for Aspergillus galactomannan monitoring and close clinical and radiological examination in case of persistence or recurrence of infection signs in high-risk patients receiving caspofungin.

Topics: Adult; Aged; Antifungal Agents; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; France; Fusariosis; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hospitals, University; Humans; Lipopeptides; Male; Mannans; Middle Aged; Mucormycosis; Pulmonary Aspergillosis

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

Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA improves survival but is difficult to make. We evaluated the effectiveness of bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these populations by retrospectively reviewing records of 67 consecutive patients, in whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL sample linked to the IPA episode was analyzed. Eighty samples were associated with proven, 12 with probable, and 32 with possible invasive fungal infections (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had proven, 11 probable, and 32 possible IPA. Using BAL GM ≥ 0.5 (cutoff for serum GM) and ≥ 0.85 (optimal cutoff identified by receiver-operating characteristic curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and 67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At these cutoffs, positive and negative predictive values were 73% (11/15) and 83% (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%, 2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was ≥ 0.85 and ≥ 0.5 in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received a mold-active agent for ≤ 3 days. BAL GM added sensitivity to serum GM and other means of diagnosing IPA, and was not impacted by short courses of mold-active agents.

Topics: Aged; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillus fumigatus; Biomarkers; Biopsy; Bronchoalveolar Lavage Fluid; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Postoperative Complications; Pyrimidines; Retrospective Studies; Sensitivity and Specificity; Triazoles; Voriconazole

This study aimed at comparing a real-time PCR assay and a PCR-ELISA assay of both serum and bronchoalveolar lavage (BAL) samples for the diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies. Using a nested case-control design, 163 patients at risk were prospectively monitored and PCR assays were performed on frozen aliquots of 459 sera which were prospectively sampled twice weekly and 42 BAL specimens sampled from 43 probable and one proven IA cases and 47 matched controls. The data from three patients classified as possible IA were excluded from the nested case-control study. The sensitivity of real-time PCR and PCR-ELISA assays in serum was 73% and 86%, respectively and specificity was 100% for both. In BAL, sensitivity was 64% for real-time PCR, 71% for PCR-ELISA and 86% for Galactomannan antigen (GMA) assays with specificities of 96%, 96%, and 93%, respectively. While slightly less sensitive, the real time-PCR assay was highly specific and considerably faster and more workable than PCR-ELISA. Combining real-time PCR and GMA detection for both serum and BAL samples enhances routine laboratory IA diagnosis.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Aspergillus; Bronchoalveolar Lavage Fluid; Child; Child, Preschool; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Humans; Infant; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Sensitivity and Specificity; Serum; Young Adult

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

Invasive aspergillosis is a life-threatening infectious complication in hematological patients undergoing immunosuppressive chemotherapy.. We report 29 cases of invasive aspergillosis diagnosed in the Sousse Farhat Hached hospital Hematology unit, Tunisia, between 2002 and 2010.. The most frequent disease (65.5%) was acute myeloid leukemia. All patients were severely neutropenic (<500/mm(3), mean duration=27 days). Pulmonary invasive aspergillosis was suggested in 28 (96.5%) cases. The most frequent respiratory signs were cough (64.3%), chest pain (53.6%), and hemoptysis (50%). The chest X-ray showed suggestive lesions in 60.7% of cases. CT scans revealed nodules with cavitation in 65% of cases, a halo sign in 20% of cases, and nodules in 15% of cases. Galactomannan antigenemia was positive in 88%, mycological examination positive in 51.6%, and seroconversion was noted in 35.7% of the cases. Invasive pulmonary aspergillosis was classified, according to EORTC/MSG criteria, as probable in 26 cases, possible in one case, and proven in one case. Aspergillus flavus was the dominant species in pulmonary invasive aspergillosis accounting for 73.7% of isolates. Extrapulmonary involvement was suggested in 39.3% of cases, the most frequent were sinusitis and brain abscess. Primary cutaneous aspergillosis was observed in one case. The overall mortality rate was 64.2%; the 12-week survival rate was 71.4%.. Our results are correlated to published data. A. flavus was the most frequent species in our region.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Brain Abscess; Child; Child, Preschool; Dermatomycoses; Enzyme-Linked Immunosorbent Assay; Female; Fungemia; Galactose; Hematologic Neoplasms; Humans; Induction Chemotherapy; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Neuroaspergillosis; Neutropenia; Sinusitis; Survival Rate; Tomography, X-Ray Computed; Tunisia; Young Adult

We evaluated the performance of a galactomannan (GM) assay in bronchoalveolar lavage (BAL) fluid compared to serum samples for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological diseases.. Two hundred and fifty-five bronchoscopies were performed on 230 patients. Bronchial and alveolar samples from BAL fluid as well as serum samples were analyzed in the GM assay.. Twenty-eight cases of IPA (11%) were diagnosed. The sensitivity, specificity, positive predictive value, and negative predictive value of the GM assay using a cut-off of 0.5 were 57.1%, 99.3%, 94.1%, and 92.5%, respectively, for the alveolar sample; 44.0%, 99.3%, 91.7%, and 91.4%, respectively, for the bronchial sample; and 60.7%, 100%, 100%, and 92.9%, respectively, for serum. The highest sensitivity (78.6%) with good specificity (98.6%) was obtained with a 'triple detection' of GM in bronchial, alveolar, and serum samples. Neutropenia and antifungal therapy for only 24h increased the sensitivity, while antifungal treatment for ≥ 2 days decreased assay performance. Moreover, a trend towards a higher volume of aspirated fluid in GM-negative BAL (p=0.092) was observed.. In contrast to recently published data, we found only moderate sensitivity, but high specificity and high positive predictive value of the detection of GM in BAL fluid. In addition, neutropenia, antifungal therapy, and BAL standardization affected GM assay performance.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Aspergillus; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cohort Studies; Female; Galactose; Hematologic Diseases; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Neutropenia; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Young Adult

Topics: Adolescent; Adult; Aged; Bronchoalveolar Lavage Fluid; Feasibility Studies; Female; Galactose; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Young Adult

Invasive pulmonary aspergillosis (IPA) is difficult to diagnose. The detection of galactomannan (GM) in serum samples is useful for diagnosing IPA. A positive test for GM antigen in BAL has also been proposed as a criterion of IPA, although it has not been fully validated. The aim of our study was to evaluate the contribution of GM antigen detection in BAL to the diagnosis of IPA in hematologic patients.. One hundred one consecutive patients treated for hematologic malignancy were explored by bronchoscopy and BAL for new pulmonary infiltrates. Both BAL fluid and serum samples were evaluated for GM using an enzyme-linked immunosorbent assay test, with an optical density index >or= 0.5 considered positive. Respiratory samples were also examined for the presence of fungi.. IPA was diagnosed in 33 patients according to European Organization for Research and Treatment of Cancer and Mycoses Study Group consensus group criteria (six proven, 23 probable, four possible). Nineteen of these 33 patients had a positive BAL GM test, whereas three patients without IPA had false-positive results. GM detection in BAL had a sensitivity of 57.6% (95% CI, 40.8%-72.8%) and a specificity of 95.6% (95% CI, 87.8%-98.5%). Among the 19 patients with IPA whose BAL was positive for GM, 15 also had a positive serum GM test. In 11 of these 19 patients, Aspergillus was identified in the respiratory samples.. Detection of GM in BAL is complementary of serum GM testing and mycologic evaluation of the respiratory samples for the diagnosis of IPA. Positive GM BAL was the sole microbiologic criterion in two of 33 patients studied.

Topics: Adult; Antigens; Bronchoalveolar Lavage Fluid; Bronchoscopy; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; Reproducibility of Results; Retrospective Studies; Severity of Illness Index

Invasive pulmonary aspergillosis (IPA) is an emerging disease associated with high mortality. The diagnosis is difficult, based on a combination of elements that are clinical, radiological and biological. For early detection of cases of IPA, during 25 months, we have systematically carried out on the LBA (N=355) of immunocompromised patients (N=313) a determination of Aspergillus galactomannan (GM) by ELISA (PlateliaAspergillus, BioRad). We observed 14 cases of probable API. The sensitivity of GM compared to direct examination (DE) and culture is, respectively, 64% versus 29% and 57%. The determination of GM is definitely more sensitive than the ED. Excellent specificity (98%) allows its implementation as a screening test in patients at risk.

Topics: Aspergillus; Bronchoalveolar Lavage Fluid; Enzyme-Linked Immunosorbent Assay; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Mannans; Mycology; Neutropenia; Postoperative Complications; Retrospective Studies; Sensitivity and Specificity

Invasive aspergillosis (IA) presents a diagnostic and therapeutic dilemma for the physicians who take care of the patients with severe underlying diseases and immunosuppression. This study aimed to evaluate the usefulness of serum galactomannan (GM) measurements in the routine practice and surveillance of IA along with possible caveats in diagnosis and treatment. Adult patients with high-risk haematological malignancies admitted to the Internal Medicine wards during the 2-year study period were followed up by daily visits for vital signs, existing or newly developing signs and symptoms, clinical and laboratory findings. Blood samples were analysed for GM levels by the ELISA method at the end of the study period. Data of 58 hospitalisation episodes in 45 patients were analysed. Proven IA was diagnosed in one patient, probable IA was diagnosed in four patients. The sensitivity was 60% and the specificity was 21% when the index cut-off for positivity was accepted as 0.5. The yield of GM testing may be influenced by many variables and each centre should evaluate the usefulness of this test in its own conditions.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Aspergillosis; Clinical Laboratory Techniques; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Population Surveillance; Sensitivity and Specificity; Young Adult

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking.. We performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions.. There were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA.. Our results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.

Topics: Adolescent; Adult; Aged; Bronchoalveolar Lavage Fluid; Case-Control Studies; Child; Female; Galactose; Hematologic Neoplasms; Humans; Immunoassay; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Prospective Studies; Sensitivity and Specificity; Young Adult

To evaluate the role of real-time polymerase chain reaction (real-time PCR) assay combined with serum galactomannan (GM) detection in the diagnosis of invasive aspergillosis (IA) with hematological malignancies or hematopoietic stem cell transplantation.. Eighty patients were enrolled. PCR and GM were performed simultaneously on 205 serum samples. The agreement between these two assays and the diagnostic value of the combination were analyzed.. There were 5 proven IA, 20 probable IA, 34 possible IA and 21 non-IA. Agreement between real-time PCR and GM was 77.5%. When both positive, the positive predictive value could reach 100%; when both negative, the negative predictive value could reach 90.9%.. PCR agrees well with GM. When these two assays are combined, invasive aspergillosis can be diagnosed more accurately.

Topics: Adolescent; Adult; Aged; Aspergillosis; Child; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Serum; Young Adult

Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].

Topics: Amoxicillin; Antibiotic Prophylaxis; Antigens, Fungal; Artifacts; Aspergillosis; Aspergillus; False Positive Reactions; Galactose; Hematologic Diseases; Hematologic Neoplasms; Humans; Immunoglobulin G; Mannans; Multiple Myeloma; Myeloma Proteins; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sensitivity and Specificity

We conducted a single-center retrospective cohort study to determine the performance characteristics of the galactomannan (GM) assay in bronchoalveolar lavage (BAL) in patients with hematologic malignancies. Patients were classified as proven, probable, possible, or no invasive pulmonary aspergillosis (IPA), according to international guidelines. A total of 173 BAL samples from 145 patients were included. There were 5 proven, 7 probable, and 35 possible cases of IPA. Using a GM index cutoff of ≥ 0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 100%, 78%, 26%, and 100%, respectively. Using a GM index cutoff of ≥ 2.0, the sensitivity and NPV remained 100%, but specificity and PPV increased to 93% and 50%, respectively. The BAL GM assay is a highly sensitive screening test for IPA in patients with hematologic malignancies. Increasing the cutoff value to 2.0 would improve the performance of this assay.

Topics: Antigens, Fungal; Aspergillus; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Canada; Cohort Studies; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunoenzyme Techniques; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Mycological Typing Techniques; Opportunistic Infections; Predictive Value of Tests; Prognosis; Retrospective Studies; Sensitivity and Specificity

Fungi of the genus Aspergillus are found everywhere in the natural environment; they cause invasive pulmonary aspergillosis (IPA), an infectious complication common in immunocompromised individuals, which has a mortality rate of up to 90% in patients with hematological malignancy. The first line of defense of innate immunity is the recognition of Aspergillus conidia by dendritic cells or alveolar macrophages. DC-SIGN is an integrin directly involved in this recognition; its degree of expression in immune cells and its functionality may be partly determined by genetic variations. The objective of this study was to determine whether the presence of polymorphisms of a single nucleotide in the DC-SIGN gene increases the risk of invasive pulmonary aspergillosis. For this purpose, the variants DC-SIGN-139A/G (rs2287886) and DC-SIGN+11C/G (rs7252229) were analyzed In 314 subjects (152 patients with hematologic malignancy and 162 healthy controls). Of the 152 hematologic cancer patients, 81 were diagnosed with demonstrated invasive pulmonary aspergillosis per EORTC/IFICG criteria, and the remaining 71 patients had no symptoms of the infection. An association was found between the variant DC-SIGN-139(A/G) and resistance to IPA. Carriers of the allele A (A/A + A/G) were significantly more resistant to the infection than patients with the G/G genotype (p = 0.0574). Analysis of the serum concentration of the galactomannan antigen supported the hypothesis that this polymorphism may be implicated in the susceptibility to suffer invasive pulmonary aspergillosis. Although the difference was not statistically significant, carriers of the allele G had a higher frequency of positive galactomannans than subjects with the genotype A/A (p = 0.1921). These results suggest that the variant DC-SIGN-139(A/G) in the DC-SIGN gene promoter influences the risk of invasive pulmonary aspergillosis and may therefore be used as a genetic biomarker to stratify patients according to risk.

Topics: Antigens, Fungal; Case-Control Studies; Cell Adhesion Molecules; Galactose; Gene Frequency; Genetic Predisposition to Disease; Hematologic Neoplasms; Humans; Immunity, Innate; Invasive Pulmonary Aspergillosis; Lectins, C-Type; Mannans; Phenotype; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Cell Surface; Risk Assessment; Risk Factors

In order to improve invasive pulmonary aspergillosis (IPA) diagnosis, a real-time polymerase chain reaction (PCR) assay detecting Aspergillus spp. was developed. Its detection limit reached 2-20 conidia. The retrospective evaluation on 64 bronchoalveolar lavage (BAL) fluids from 57 patients at risk for IPA, including 20 probable and five proven IPA patients, revealed a 88% or 38% sensitivity in direct examination (DE)/culture-positive or culture-negative BAL, respectively, whereas galactomannan (GM) sensitivity reached 88% or 58%, respectively. Influence on the Aspergillus-PCR yield of BAL fluid volume, cellular count and DNA content (evaluated by human beta-globin quantification) was assessed. Significantly higher beta-globin levels were detected in Aspergillus PCR-positive (median 5,112 pg/microl) than negative (median 1,332 pg/microl) BAL fluids, suggesting that the beta-globin level could reflect BAL yields and DNA extraction. Using beta-globin for the interpretation of fungal PCR could improve the negative predictive value of this test.

Topics: Adult; Aged; Aged, 80 and over; Aspergillosis; Aspergillus; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; DNA, Fungal; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; 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

The detection of circulating galactomannan (GM) in serum samples is an important step in the diagnosis of invasive aspergillosis (IA). The assay has been mainly explored in neutropenic patients, and is now used to monitor patients at high risk for IA. However, the performance of the assay varies greatly among studies. The objective of this study was to explore the impact of the neutrophil count on the GM serum index at the time of IA diagnosis. Ninety-nine episodes of proven or probable, microbiologically documented IA in 91 patients with haematological malignancies were studied retrospectively. Three groups were identified: groups 1-3, with <100 polymorphonuclear neutrophils (PMN)/mm(3) (n = 18), between 100 and 500 PMN/mm(3) (n = 21), or >500 PMN/mm(3) (n = 60), respectively. The mean GM index was significantly higher in group 1 than in the other groups (p <0.05). This finding did not change after stratifying the analysis with regard to the use of antibiotics likely to give false-positive GM results or with regard to treatment effective against fungi before the diagnosis of IA. This finding could be considered in the routine use of the GM antigenaemia test in non-neutropenic patients; a negative result or a low GM index should not eliminate the diagnosis of IA. This limitation calls for other microbiological tests, including analysis of bronchoalveolar lavage fluid, to establish a definitive diagnosis of IA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifungal Agents; Antigens, Fungal; Aspergillosis; Female; Galactose; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Leukocyte Count; Male; Mannans; Middle Aged; Neutropenia; Neutrophils; Statistics, Nonparametric; Stem Cell Transplantation

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

The diagnosis of invasive aspergillus remains a challenge in the care of high-risk patients. Outcomes are improved when invasive aspergillus is diagnosed early, prompting the initiation of appropriate antifungal therapy. We evaluated the utility of prospective monitoring for invasive aspergillosis (IA) using biomarkers such as serum galactomannan (GM) and/or blood polymerase chain reaction (PCR) in high-risk pediatric patients.. Patients with high-risk leukemia (HRL) or allogenic hematopoietic cell transplant (HCT) recipients were prospectively monitored twice weekly for IA using GM and PCR for Aspergillus species.. Sixty-eight patients had collected >or=2 specimens. The 1086 specimens were collected; 627 from HRL (58%) and 459 (42%) from HCT recipients. Median specimens/patient was 11.0 (2 to 58), and median follow-up/patient was 98.5 days (14 to 437). Fifty-six percent of samples were obtained from patients receiving mold-active agents; 32% HRL and 89% HCT. There were no proven, 3 probable, and 20 possible episodes of IA. Thirteen specimens (1.2%) from 4 patients (5%) were GM+. None were positive by PCR.. The prospective use of GM and PCR in this high-risk pediatric population did not identify cases of proven IA. A high false positive rate was not detected. It is speculated that changes in clinical practice, such as early use of empiric and/or prophylactic mold-active agent and frequent imaging studies have impacted the epidemiology of IA. In a population with low incidence of IA, the use of these assays as a screening device on blood may not further enhance current outcomes.

Topics: Adolescent; Adult; Aspergillosis; Aspergillus; Child; Child, Preschool; DNA, Fungal; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Mannans; Polymerase Chain Reaction; Prospective Studies; Risk Factors; RNA, Ribosomal, 28S; Transplantation, Homologous; Young Adult

To analyse the predominant radiological pattern of pulmonary lesions in adult hematologic patients at risk for invasive aspergillosis (IA) together with the results of serial serum Aspergillus galactomannan antigen testing (GM).. In a prospective study for patients at high risk of aspergillus pulmonary infection, serum GM were performed 2-3 times per week during the periods of high risk for IA and high-resolution CT (HRCT) was performed in case of abnormal chest X-ray (CXR) and/or persistent fever after 5 days of antibiotic treatment. Changes on HRCT scan were classified as airway IA and angioinvasive IA. IA was classified as proven or probable in accordance with the definitions stated by the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC-MS). Positive GM testing was not considered as microbiological criterion.. 38 hematological patients were diagnosed of probable (n=28) or proven (n=10) IA. 55% patients had a neutrophil count less than 500 mm(-3) (n=21), and 37% patients > or =2 risk factors for IA. All probable IA were diagnosed by bronchoalveolar lavage (BAL). Proven IA was reached by positive histopathologic and culture results of samples obtained by autopsy (n=4), percutaneous (n=3) or transbronchial biopsy (n=3). 18 patients had airway IA, and 60% had a GM level > or =1.5. 20 patients were diagnosed of angioinvasive IA from which 80% had a GM level > or =1.5.. Serum GM levels may be lower in patients with airway IA than in those with an angioinvasive form. HRCT and serum GM are complementary tests in the diagnosis of IA.

Topics: Adolescent; Adult; Aged; Aspergillosis; Aspergillus; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity; Statistics as Topic; Tomography, X-Ray Computed; Young Adult

Invasive aspergillosis (IA) is the leading direct or contributory cause of death in patients with haematological malignancies. Early diagnosis remains difficult and often elusive due the heterogeneity of clinical presentations and the low sensitivity of both histological examination and cultures of specimens obtained from patients at risk. We report two cases of IA, both of which lacked both histological and cultural evidence of IA from pulmonary specimens. In both patients, detection of galactomannan (GM) by enzyme immunoassay (EIA) on pulmonary tissue homogenates led to the diagnosis of IA, which was confirmed by Aspergillus DNA (real time PCR). In conclusion, we provide preliminary evidence that lung homogenates may be prepared for GM EIA assays, which may contribute to quick diagnosis of IA on otherwise negative samples. We feel that our results open up the opportunity of a prospective and comparative evaluation of this diagnostic technique.

Topics: Adult; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; DNA, Fungal; Female; Galactose; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Lung; Male; Mannans; Middle Aged; Polymerase Chain Reaction

A reliable diagnosis of invasive aspergillosis (IA) is hampered by the difficulty in obtaining suitable tissue samples. To evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the LightCycler PCR for the diagnosis of IA, 536 blood samples were collected over a 22-month period from 62 paediatric patients (median age 10 years, range 1-18) considered at risk of IA. The galactomannan antigen (GM) and fungal DNA were assessed on serial blood samples. IA was diagnosed in eight of 62 patients (13%): proven, five, probable, three. Sensitivity, specificity, PPV and NPV of LightCycler PCR varied according to the number of positive samples used to define positivity: 88%; 37%; 17% and 95% for single sample positivity; and 63%, 81%, 33% and 94% for serial sample positivity respectively. The concordance between positivity of LightCycler PCR assay and the diagnosis of IA was 79%. The single positivity of LightCycler PCR assay showed a good sensitivity for the diagnosis of IA in paediatric patients. The high NPV makes LightCycler PCR a promising tool in addition to GM testing to design a strategy of pre-emptive antifungal therapy, although further validation studies are needed.

Topics: Adolescent; Aspergillosis; Child; Child, Preschool; DNA, Fungal; Female; Galactose; Hematologic Neoplasms; Humans; Infant; Male; Mannans; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity

PREMISES AND OBJECTIVES: Timely diagnosis is of critical importance for the prognosis of invasive aspergilosis (IA) patients. Over recent years, IA detection of galactomannan using the ELISA method has assumed growing importance. The objective of the study was to analyse the usability of the method in current clinical practice of a hemato-oncological ward.. From May 2003 to October 2006, blood samples were taken from patients at IA risk to detect galactomannan (GM) in serum using the ELISA method. The patients who underwent the tests were classified by the probability of IA presence on the basis of the results of conventional diagnostic methods and section findings.. A total of 11,360 serum samples from 911 adult patients were tested for GM presence. IA (probable/proven) was diagnosed in 42 (4.6%) of them. The rates of sensitivity, specificity, positive and negative predictive value of galactomannan detection for IA diagnosis in our ward were, respectively, 95.2%, 90.0%, 31.5% and 99.7%. The principal causes of the limited positive predictive value of the test were the high percentage of false-positive test results (mainly caused by concomitant administration of some penicillin antibiotics or Plasma-Lyte infusion solution), as well as the fact that a large percentage of patients we examined fell within the group of patients with hematological malignity with a very low prevalence of IA.. GM detection in serum is associated with high sensitivity and excellent negative predictive value in IA diagnosis in hemato-oncological patients. Knowledge and elimination of possible causes of false-positive results as well as focusing the screening on patients at greatest risk of infection are necessary for an even better exploitation of the test.

Topics: Adult; Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Enzyme-Linked Immunosorbent Assay; Galactose; Hematologic Neoplasms; Humans; Mannans; Opportunistic Infections; Predictive Value of Tests; Sensitivity and Specificity

Galactomannan is an Aspergillus-specific polysaccharide released during aspergillosis and is detected by the quantitative serum galactomannan index (GMI) test. Preclinical and preliminary clinical reports have suggested a good correlation between GMI and aspergillosis outcome.. We reviewed the literature to assess the strength of correlation between GMI and aspergillosis outcome using the kappa correlation coefficient. We included 27 studies that enrolled patients with hematological cancer and proven or probable aspergillosis and that used sequential GMI testing. We examined the 3 following outcomes: survival (survival vs. death), global outcome (survival vs. death [including autopsy findings]), and autopsy outcome (autopsy findings only).. Overall, 257 patients fulfilled criteria for proven or probable aspergillosis and were eligible for outcome evaluation. Correlation between GMI (within

Topics: Aspergillosis; Aspergillus; Galactose; Hematologic Neoplasms; Humans; Mannans; Meta-Analysis as Topic; Prognosis; Survival Analysis; Treatment Outcome

The aim of this study was to determine whether interleukin-1 alpha (IL1alpha), interleukin-1 beta (IL1beta), and IL1 receptor antagonist (IL1Ra) polymorphisms are implicated in invasive pulmonary aspergillosis (IPA) pathogenesis.. Subjects comprised 110 hematological patients and 148 healthy controls. Genotypic and allelic frequencies were similar between hematological patients and controls. IPA was diagnosed in 59 of the 110 patients according to consensus criteria published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/IFICG).. Individual locus analysis showed that IL1alpha and IL1Ra polymorphisms were not associated with the presence of IPA (p = 0.560 and p = 0.680, respectively). However, a trend towards a higher presence of IL1beta( - ) (511TT) genotype (or IL1beta(-511T) allele) in the IPA group than in the non-IPA patient group (p = 0.092 and p = 0.095, respectively) was found. Haplotype analysis revealed that VNTR2/-889C/-511T haplotype was strongly associated with susceptibility to develop IPA infection (p = 0.020). Haplotype analysis also showed an association between VNTR2/-889C/-511C haplotype and resistance to IPA infection (p = 0.028). Furthermore, patients with IL1Ra VNTR2/2 and IL1beta(-511)T/T genotypes had a higher positive serum galactomannan percentage versus patients with other genotypes. Finally, C-reactive protein (CRP) production was significantly associated with IL1 gene cluster polymorphisms, although CRP values were similar between IPA and non-IPA groups.. These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.

Topics: Aspergillosis; Aspergillus; C-Reactive Protein; Drug-Related Side Effects and Adverse Reactions; Female; Galactose; Genetic Predisposition to Disease; Haplotypes; Hematologic Neoplasms; Humans; Immunocompromised Host; Interleukin-1alpha; Interleukin-1beta; Lung Diseases, Fungal; Male; Mannans; Multigene Family; Polymorphism, Single Nucleotide; Receptors, Interleukin-1 Type I; Statistics as Topic

In this prospective study including 78 adult patients with haematological malignancy (90 episodes) we performed galactomannan (GM) (Platelia Aspergillus) screening twice weekly for the diagnosis of invasive aspergillosis. There were five proven and four probable invasive aspergillosis cases. The sensitivity, specificity and positive and negative predictive values were 100, 88, 47 and 100%, respectively. There were eight patients with false positive GM (10.2%). In six patients the false GM reactivity was due to the administration of piperacillin-tazobactam (P-T). A significant association was found between false positive GM (= or > 0.5) and the administration of P-T (p < 0.01). Two other patients with no invasive aspergillosis (2.5%) and false GM reactivity had graft versus host disease (GVHD) and one of them had also mucositis grade IV. The kinetic patterns of false positive GM due to P-T is discussed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Artifacts; Aspergillosis; Biomarkers; Combined Modality Therapy; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Fungemia; Galactose; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Mucositis; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

Determining the outcome of patients with aspergillosis can be particularly difficult because patients with aspergillosis are at risk for other conditions that mimic this infection. Galactomannan is an Aspergillus-specific antigen released during invasive aspergillosis and is detected by the quantitative serum galactomannan index (GMI) test.. Using a kappa correlation coefficient test (KCC), the strength of correlation was determined between GMI and survival outcome of aspergillosis among 56 adults with hematologic cancer (90% had myeloma) who underwent serial GMI monitoring until hospital discharge or death.. All 56 patients received antineoplastic therapy (myeloablative followed by stem cell transplantation [autologous in 21 patients and allogeneic in 3 patients] or nonmyeloablative therapy [32 patients]). The overall correlation between survival outcome and GMI was excellent (KCC = 0.8609; 95% confidence interval [95% CI], 0.7093-1.000 [P < .0001]) and was comparable among neutropenic and nonneutropenic patients (KCC = 0.8271; 95% CI, 0.6407-1.000 [P < .0001] and KCC = 1.0; 95% CI, 1-1 [P = .0083], respectively).. The survival outcome of patients with aspergillosis strongly correlated with serum GMI. These findings have important implications for patient care and clinical trials of mold-active antifungal agents.

Topics: Adult; Aged; Antigens, Fungal; Aspergillosis; Aspergillus; Combined Modality Therapy; Dexamethasone; Female; Galactose; Glucocorticoids; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Multiple Myeloma; Predictive Value of Tests; Prognosis; Stem Cell Transplantation; Survival Analysis

We compared the sensitivity and specificity of galactomannan enzyme-linked immunosorbent assay (GM-ELISA) with that of a newly developed version of the commercially available latex agglutination test (GM-LATEX) in our patient population. Serum samples were collected from 144 healthy adult donors (controls); another 17 consecutive hematologic malignancy (HM) patients with probable or proven invasive aspergillosis (IA) were tested. Clinical, microbiological, and pathological data were obtained. The sensitivity of the GM-LATEX test was 53% per patient and 66% per sample and that of the GM-ELISA test was 41% per patient and 21% per sample. Both tests demonstrated a specificity of 99%. The GM-LATEX test demonstrated a superior sensitivity in terms of detecting galactomannan and thus may be useful in the diagnosis of IA in patients with HM.

Topics: Adult; Aspergillosis; Enzyme-Linked Immunosorbent Assay; Galactose; Hematologic Neoplasms; Humans; Latex Fixation Tests; Mannans; Sensitivity and Specificity

Invasive aspergillosis (IA) is associated with high mortality. Successful outcome with treatment is linked to early diagnosis. The utility of classic diagnostic methods, however, is limited.. To aid in the diagnosis of IA, we retrospectively assessed our diagnostic service, using real-time polymerase chain reaction (PCR) and galactomannan sandwich enzyme-linked immunosorbent assay (ELISA).. A total of 203 patients at risk of invasive fungal infection were screened by PCR, and 116 of the patients were also tested by ELISA. The patient group comprised 176 patients with hematological malignancy and 28 control patients with evidence of invasive candidal infection. Consensus European Organisation for Research and Treatment of Cancer and Mycoses Study Group criteria were used to classify fungal infection, which, by definition, excluded the PCR result. The PCR method was sensitive (up to 92.3% sensitivity) and specific (up to 94.6% specificity) and had good agreement with the galactomannan ELISA (76.7%) and high-resolution computed tomography scan results.. A negative PCR result can be used to rule out IA and to limit the need for empirical antifungal therapy; thus, it has a role in diagnosing IA infections, especially in combination with antigen testing. PCR-positive cases classified as "false positives" regularly reflect the limitations of classic microbiological procedures or restricted use of consensus clinical methods employed to classify infection.

Topics: Adolescent; Adult; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Aspergillus; Blood; Candidiasis; Child; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Galactose; Hematologic Neoplasms; Humans; Mannans; Middle Aged; Opportunistic Infections; Polymerase Chain Reaction; Retrospective Studies; RNA, Fungal; Sensitivity and Specificity; Stem Cell Transplantation; Tomography, X-Ray Computed

Current laboratory and radiological methods for diagnosis of invasive aspergillosis (IA) lack sensitivity and specificity.. We prospectively evaluated the diagnostic value of twice-weekly screening for circulating Aspergillus fumigatus and A. flavus DNA with a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA).. Among the 201 adult patients with hematological malignancies who were included in the study, 55 IA cases were diagnosed. On the basis of the analysis of 1205 serum samples from 167 patients, the sensitivity, specificity, and positive and negative predictive values of the PCR-ELISA for proven and probable IA cases were 63.6%, 89.7%, 63.6%, and 89.7%, respectively, when samples with 2 consecutive positive results were used. The use of a combination of the PCR-ELISA and a galactomannan (GM) assay increased the sensitivity to 83.3%, increased the negative predictive value to 97.6%, and decreased the specificity to 69.8%. In most patients with IA, PCR-ELISA positivity anticipated or was simultaneous with the initiation of antifungal therapy, the abnormalities found by computed tomography, the mycological/histological diagnosis, and the GM positivity. Overall, 56.3% of the patients had at least 1 positive sample, and the false single-positive rate was 44.8%.. In addition to serial screening for GM antigenemia and radiological surveillance, PCR-ELISA may improve the rates of early diagnosis of IA and the management of patients with hematological malignancies.

Topics: Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; DNA, Fungal; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Galactose; Hematologic Neoplasms; Humans; Mannans; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

Topics: Academic Medical Centers; Aspergillosis; Aspergillus; Galactose; Hematologic Neoplasms; Immunoenzyme Techniques; Mannans; Opportunistic Infections

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

Early diagnosis of invasive pulmonary aspergillosis (IPA) is important as prompt treatment with antifungal drugs may increase patient survival. Our study investigated the efficiency of routine testing of the Aspergillus galactomannan antigen (AGA) test in combination with chest CT scans for IPA diagnosis.. From February 2002 to June 2004, 74 hemato-oncologic patients undergoing allogeneic stem cell transplantation were prospectively studied with serum AGA twice weekly from admission until death or discharge and weekly afterward when possible. Chest CT scans were performed when fever of unknown origin had lasted beyond 3 days of antibacterial therapy.. Seven patients were classified with possible IPA and two patients, proven IPA. Fourteen patients showed positive results for AGA (OD index>or=1.0 on two subsequent sera). The sensitivity and specificity of the test were 100% and 93%, respectively; the positive and negative predictive values were 64% and 100%, respectively. All patients with possible/proven IPA showed abnormal CT signs; in four cases, imaging signs followed AGA positivity (median 5 days), whereas in five cases they preceded serologic positivity (median, 8 days). In the nine patients with IPA, antifungal therapy was promptly instituted, including lipid formulations of amphotericin B (n=5) or caspofungin (n=4). In only two of the nine patients (22%) with IPA, the primary cause of death was fungal infection.. The combination of AGA detection and early chest CT scans might be considered useful tools to detect minimal changes of IPA. Based on these findings, aggressive antifungal therapy should be initiated.

Topics: Adult; Aged; Antigens, Fungal; Aspergillosis; Aspergillus; Galactose; Hematologic Neoplasms; Humans; Lung Diseases; Mannans; Middle Aged; Neoplasms; Retrospective Studies; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome

Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied.. In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by 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.. We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT.. We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Aspergillosis; Female; Galactose; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Multivariate Analysis; Odds Ratio; Sensitivity and Specificity; Tomography, X-Ray Computed

We report the occurrence of a high rate of false-positive test results during the surveillance of hematology patients for galactomannan (GM) antigenemia. Among 218 patients surveyed from June 2002 through June 2003, 42 (19.3%) had > or =1 serum sample positive for GM (optical density index, >1.5). Of these patients, 38 had no additional evidence of invasive aspergillosis, and, therefore, their test results were considered to be false-positives. Case-control analysis showed that treatment with piperacillin-tazobactam was the only risk factor significantly associated with receiving false-positive test results. When tested for GM antigen, 3 of 4 piperacillin-tazobactam batches had positive results. Physicians should be aware of the possible interference of treatment with piperacillin-tazobactam when interpreting the results of the GM assay.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antigens, Fungal; Aspergillus; Case-Control Studies; False Positive Reactions; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Microbiological Techniques; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sensitivity and Specificity

Invasive aspergillosis (IA) is a considerable clinical problem in neutropenic patients with haematological malignancies but its diagnosis remains difficult. We prospectively evaluated a LightCycler polymerase chain reaction (PCR) assay, a nested-PCR assay and a galactomannan (GM) enzyme-linked immunosorbent assay (ELISA) to validate their significance in diagnosing IA. During 205 treatment episodes in 165 patients from six centres, a nested-PCR assay and GM testing was performed at regular intervals. Positive nested-PCR results were quantified by a LightCycler PCR assay. Patient episodes were stratified according to the 2002 European Organization for Research and Treatment of Cancer/Mycosis Study Group consensus criteria and the PCR and serology results were correlated with the clinical diagnostic classification. Sensitivity and specificity rates for the nested-PCR assay were up to 63.6% [95% confidence interval (CI): 30.8-89%) and 63.5% (95% CI: 53.4-72.7%) respectively, and 33.3% and 98.9% (95% CI: 7.5-70.1% and 94.2-99.9%) for GM respectively. The LightCycler PCR assay yielded positive results in 21.4%, lacking discrimination by quantification across the different clinical categories. In this prospective comparison, PCR was superior to GM with respect to sensitivity rates. In patients at high risk for IA, positive results for Aspergillus by PCR of blood samples are highly suggestive for IA and contribute to the diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Neutropenia; Polymerase Chain Reaction; Prospective Studies

The recent advent of an improved commercial serum enzyme-linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut-off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut-off points, lower than previously accepted, are proposed: (a) a 'static' cut-off at 0.8 and (b) a 'dynamic' cut-off at 0.5. A single assay with an optical density (OD) index > or = 0.8 warrants the initiation of anti-Aspergillus therapy. A further lowering of the 'static' threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD > or = 0.5 ('dynamic' threshold) increased the specificity and the PPV to 98.6% and the efficiency to 98%. Applying both cut-offs to a subgroup of 21 'possible' fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut-offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling.

Topics: Adolescent; Adult; Aged; Aspergillosis; Biomarkers; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Neutropenia; Opportunistic Infections; Prospective Studies; Sensitivity and Specificity

We analyzed the performance of (1, 3)-Beta-D-glucan (measurement by the alkaline-kinetic chromogenic Limulus method (FUNGITEC G test-MK, Fungitec) and the kinetic turbidimetric Limulus method [Beta-Glucan test WAKO, Wako]) and we carried out Aspergillus galactomannan antigen detection (enzyme-linked immunosorbent assay, ELISA test) for the early diagnosis of invasive aspergillosis in patients with hematological diseases at the time of febrile episodes of unknown origin that did not respond to antibacterial therapy for more than 3 days. During a one-year period (April 2002 to March 2003), a total of 69 febrile episodes in 58 patients were studied; 8 cases of invasive aspergillosis were diagnosed according to the definition of the European Organization for Research and Treatment of Cancer/Mycosis Study Group, and 61 cases were found to be non-mycotic diseases. Based on the analysis of 69 results with confirmed disease status, the overall performance of the Fungitec, the Wako, and the ELISA test were as follows: sensitivity was 0.88, 0.63, and 0.50, respectively, whereas the specificity was 0.85, 0.98, and 1.0, respectively. Moreover, there was a strong relationship between the log-transformed values of the (1, 3)-Beta-D-glucan levels measured by the two methods (r = 0.92 [95%CI, 0.89-0.94] ; p<0.001). For the statistical analysis of these serological tests a receiver operating characteristic curve (ROC) was used, as well as the resulting area under the ROC curve (ROC AUC). The ROC AUC and the cut-off values that gave the highest accuracy were as follows: 0.92, 24.9 pg/ml for the Fungitec, 0.84, 7.3 pg/ml for the Wako, and 0.89, 0.9 COI for the ELISA test, respectively. In conclusion, these results indicate that both of the two (1, 3)-Beta-D-glucan measurement approaches served equally well as surveillance tools for determining the extent of invasive aspergillosis; in addition, the log-transformed value of these tests can be used for comparison. Moreover, the ELISA test was found to have clinical utility, both as a surveillance and as a diagnostic tool when invasive aspergillosis was suspected. It should be noted that the galactomannan assay had sensitivity-related limitations; lowering the cut-off value is expected to increase the diagnostic value for use in cases of invasive aspergillosis.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; Aspergillosis; beta-Glucans; Female; Galactose; Glucans; Hematologic Neoplasms; Humans; Limulus Test; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Sensitivity and Specificity

The diagnosis of invasive aspergillosis in neutropenic individuals is difficult and lengthy since non-invasive diagnostic tests lack sensitivity and specificity. The diagnosis of invasive aspergillosis in 154 prolonged neutropenic patients was prospectively bi-weekly validated by screening circulating galactomannan. The global sensitivity was 73% and specificity was 96%. The positive and negative predictive values were 73% and 98% respectively. False positive reactions occurred at a rate of 2%. Antigenemia was detected before clinical suspicion of invasive aspergillosis (median, 6 days before) in 30% of patients and anticipated the onset of radiologic signs 9 days in 60% of patients.. the prospective screening of galactomannan is a sensitive and non-invasive tool for early diagnosis of invasive aspergillosis in high-risk adult hematology patients.

Topics: Adult; Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Bone Marrow Transplantation; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Fungemia; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Neutropenia; Predictive Value of Tests; Prospective Studies; Risk; Sensitivity and Specificity; Time Factors

Screening for galactomannan (GM) has been adopted by many European centers as part of the management plan for allogeneic stem cell transplant recipients. However, the temporal onset of GM antigenemia remains unknown. A series of allogeneic stem cell transplant recipients were monitored prospectively, and the relationship between antigenemia and other diagnostic triggers for initiation of antifungal therapy was analyzed. GM detection had a sensitivity of 94.4% and a specificity of 98.8%. Positive and negative predictive values were 94.4% and 98.8%, respectively. This statistical profile was better than that of other triggers, including unexplained fever, new pulmonary infiltrates, isolation of Aspergillus species, and abnormalities seen on computed tomography. Antigenemia preceded diagnosis on the basis of radiologic examination or Aspergillus isolation by 8 and 9 days in 80% and 88.8% of patients, respectively. Antigenemia preceded therapy in 83.3% of patients. Detection of GM was especially useful when patients were receiving steroid treatment or when coexisting conditions masked the diagnosis of invasive aspergillosis. Prospective screening for GM allows earlier diagnosis of aspergillosis than do conventional diagnostic criteria.

Topics: Adolescent; Adult; Age Distribution; Anemia, Aplastic; Aspergillosis; Biomarkers; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Neoplasms; Stem Cell Transplantation; Survival Analysis; Time Factors; Transplantation, Homologous

The diagnosis of invasive aspergillosis (IA) in patients with hematologic disorders is not straightforward; lack of sensitive and specific noninvasive diagnostic tests remains a major obstacle for establishing a precise diagnosis. In a series of 362 consecutive high-risk treatment episodes that were stratified according to the probability of IA based on recently accepted case definition sets, the potential for diagnosis of serial screening for circulating galactomannan (GM), a major aspergillar cell wall constituent was validated. After incorporating postmortem findings to allow a more accurate final analysis, this approach proved to have a sensitivity of 89.7% and a specificity of 98.1%. The positive and negative predictive values equaled 87.5% and 98.4%, respectively. False-positive reactions occurred at a rate of 14%, although this figure might be overestimated due to diagnostic uncertainty. More or less stringent criteria of estimation could highly influence sensitivity, which ranged from 100% to 42%; the impact on other test statistics was far less dramatic. All proven cases of IA, including 23 cases confirmed after autopsy only, had been detected before death, although serial sampling appeared to be necessary to maximize detection. The excellent sensitivity and negative predictive value makes this approach suitable for clinical decision making. Unfortunately, given the species-specificity of the assay, some emerging non-Aspergillus mycoses were not detected. In conclusion, serial screening for GM, complemented by appropriate imaging techniques, is a sensitive and noninvasive tool for the early diagnosis of IA in high-risk adult hematology patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; Autopsy; Biomarkers; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Neutropenia; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA.. We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations.. Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0.. Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Antineoplastic Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; Child; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Mannans; Middle Aged; Neutropenia