Galactomannan Antigen Test Research Articles

Potential of polymerase chain reaction and galactomannan for the diagnosis of invasive aspergillosis in patients with febrile neutropenia.

The incidence of invasive aspergillosis (IA) has increased over the last years, especially in immuncompromised patients with high mortality rates. Because of difficulties about the diagnosis; serological methods [galactomannan (GM) antigen test] and polymerase chain reaction (PCR) developed in recent years. MycAssay Aspergillus PCR performance in the diagnosis of IA was evaluated and compared with the GM and in-house PCR. This study was conducted with 358 serum samples obtained from 99 patient with febrile neutropenic episodes who were followed in haematology and bone marrow transplantation units. Patients were classified by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 18 of them is proven and probable IA. GM antigen test and two different real-time PCR; one of them is fist commercial PCR for IA; Mycassay Aspergillus and the other one is in-house real-time PCR performed. Sensitivity values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and 23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR and sensitivity is increased by using a combination of diagnostic methods. GM antigen test and real-time PCR could be beneficial for early diagnosis and treatment of IA. For routine usage of PCR as diagnostic assay more studies needed in future.

Molecular and nonmolecular diagnostic methods for invasive fungal infections.

Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use.

Drug–laboratory interaction between beta-lactam antibiotics and the galactomannan antigen test used to detect mould infections

Several studies have demonstrated that piperacillin/tazobactam produces a false-positive result for the galactomannan antigen test. However, the most recent literature has demonstrated that this interaction is no longer a concern. There is little information regarding the drug–laboratory interaction with the generics of piperacillin/tazobactam or other broad-spectrum beta-lactams, such as ceftaroline, doripenem, imipenem/cilastatin, and meropenem. The purpose of this study was to determine if a drug–laboratory interaction exists with these antibiotics. Tests showed that one lot of imipenem/cilastatin by Hospira Healthcare India Private Limited produced a false-positive result for the galactomannan antigen test. All other medications tested, including piperacillin/tazobactam from seven manufacturers and imipenem/cilastatin by Hospira Inc., did not produce positive results. Since the reason for this drug–laboratory interaction with imipenem/cilastatin is unknown, more studies are needed to further investigate this interaction. Providers also should be educated of these findings: no drug–laboratory interaction with piperacillin/tazobactam and a possible drug–laboratory interaction with imipenem/cilastatin (Hospira Healthcare India Private Limited).

Earlier Diagnosis of Invasive Fusariosis with Aspergillus Serum Galactomannan Testing

Cross-reactivity of Fusarium species with serum galactomannan antigen (GMI) test has been observed. We sought to evaluate if GMI could help to early diagnose invasive fusariosis and to monitor treatment response. We reviewed the records of all patients with invasive fusariosis between 2008 and 2012 in three Brazilian hospitals. We selected patients who had at least 1 GMI test within 2 days before or after the date of the first clinical manifestation of fusariosis, and analyzed the temporal relationship between the first positive GMI test and the date of the diagnosis of invasive fusariosis, and the kinetics of GMI in relation to patients' response to treatment. We also selected 18 controls to determine the sensitivity and specificity of the test. Among 18 patients, 15 (83%) had at least one positive GMI (median 4, range 1–15). The sensitivity and specificity of was 83% and 67%, respectively. GMI was positive before the diagnosis of invasive fusariosis in 11 of the 15 cases (73%), at a median of 10 days (range 3–39), and after the diagnosis in 4 cases. GMI became negative in 8 of the 15 patients; 3 of these 8 patients (37.5%) were alive 90 days after the diagnosis of fusariosis compared with 2 of 7 (29%) who did not normalize GMI (p = 1.0). GMI is frequently positive in invasive fusariosis, and becomes positive before diagnosis in most patients. These findings may have important implications for the choice of antifungal therapy in settings with high prevalence of invasive fusariosis.

Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis

A serum galactomannan (GM) antigen test has been widely used to diagnose invasive pulmonary aspergillosis. However, there are limited data on the use of the serum GM antigen test for the serologic diagnosis of chronic pulmonary aspergillosis (CPA). Data were collected from all consecutive patients with a clinical suspicion of CPA who underwent a serum GM antigen test. In total, 334 patients who were suspected to have CPA were eligible for this study and 168 (50%) patients were finally diagnosed with CPA. The serum GM antigen test was positive in 38 (23%) patients with CPA and in 25 (15%) patients without CPA. The sensitivity of the serum GM antigen test was 23% (95% confidence interval [CI], 17-30%), and its specificity was 85% (95% CI, 79-90%), with positive and negative predictive values of 60% (95% CI, 47-72%) and 52% (95% CI, 46-58%), respectively. The accuracy of the test was 54%. The area under the receiver operating characteristic curve was 0.538 (95% CI, 0.496-0.580). The serum GM antigen test could not be used for the serologic diagnosis of CPA.

P262 Invasive fungal infections in haematological malignancies patients: Rapid diagnosis by galactomannan antigen testing and pan-fungal RT-PCR

P262 Invasive fungal infections in haematological malignancies patients: Rapid diagnosis by galactomannan antigen testing and pan-fungal RT-PCR

A 6-year antifungal stewardship programme in a teaching hospital

To describe the antifungal stewardship programme in our hospital and to assess its impact on total antifungal prescriptions and their cost, and on the process of care measures regarding the diagnostic and therapeutic management of invasive aspergillosis and candidaemia. We conducted a prospective observational study describing the multifaceted antifungal stewardship programme in place at our French teaching tertiary-care hospital since 2005. Several actions were implemented successively, including the systematic evaluation of all costly antifungal prescriptions (echinocandins, lipid formulations of amphotericin B, posaconazole and voriconazole). A total of 636 antifungal prescriptions were discussed by the antifungal management team from 2005 to 2010 inclusive, mainly from the haematology department (72 %). In 344/636 cases (54 %), a piece of advice was fed back to the physician in charge of the patient, with an 88 % compliance rate. Optimal standard of care was achieved for galactomannan antigen testing, performance of chest computed tomography (CT) scan and voriconazole therapeutic drug monitoring for invasive aspergillosis, with no combination therapies used since 2008. Regarding candidaemia, optimal standard of care was achieved for the timing of antifungal therapy, recommended first-line therapy, duration of therapy and the removal of central venous catheters. Total antifungal prescriptions (in defined daily doses, DDD) and their cost were contained between 2003 and 2010. The implementation of an antifungal stewardship programme was feasible, sustainable and well accepted. We observed an improved quality of care for some process of care measures, and antifungal use and cost were contained in our hospital.

Aspergillus galactomannan antigen assay and invasive aspergillosis in pediatric cancer patients and hematopoietic stem cell transplant recipients

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.

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

Galactomannan Antigen Testing for Diagnosis of Invasive Aspergillosis in Pediatric Hematology Patients

Invasive aspergillosis (IA) can cause significant morbidity and mortality in immunocompromised children. The galactomannan (GM) enzyme immunoassay (EIA) has been shown in adult studies to be a useful adjunct in diagnosing IA. Data on this assay in children are limited by small sample sizes and conflicting results; false-positive assays were a concern in historical studies. We sought to evaluate the GM EIA in a large cohort of children who received intensive chemotherapy and/or hematopoietic stem cell transplant. A focus was placed on evaluating the assay specificity, and the potential of measuring GM antigen in urine. A multicenter prospective observational study in children with anticipated prolonged neutropenia was performed. Serum specimens were collected twice weekly, and urine was collected once weekly during neutropenic periods. Operating characteristics were calculated using the GM EIA optical density index cutoffs of 0.5 and 1.0 for both serum and urine specimens. At least one serum or urine specimen was tested from 198 patients. Ten patients had one or more repeatedly positive serum specimens, while 37 patients had one or more repeatedly positive urine specimens. The specificity of serum and urine testing was 95% and 80%, respectively. Although the urine test resulted in a higher false positivity rate, it successfully identified the only case of probable IA. Data suggest that the serum GM EIA does not provide frequent false-positive results as previously reported. Screening for galactomannan, or a related antigen in urine, needs to be further evaluated as it may be amenable to development of surveillance strategies.

Editorial Commentary: Galactomannan Antigen Testing for Diagnosis of Invasive Aspergillosis in Pediatric Hematology Patients

Invasive fungal diseases, in particular those due to Aspergillus spp., are increasing in incidence and constitute an important cause for morbidity and mortality in children and adolescents with hematologic malignancies and those undergoing allogeneic hematopoietic stem cell transplantation (HSCT) [1]. A contemporary retrospective analysis demonstrated that corticosteroid therapy, neutropenia, immunosuppressive therapy, malignancy, and allogeneic HSCT are the most common risk factors for invasive aspergillosis in pediatric age groups [2]. The overall case fatality rate of invasive aspergillosis in this study was 53%, which is similar to that seen in adult patients. Invasive aspergillosis significantly contributes to the in-house mortality of children with acute lymphoblastic and myeloid leukemia, lymphoma, allogeneic HSCT, and solid organ transplantation. In a retrospective cohort study using a national database of hospital inpatient stays during 2000, 18% (122 of 666) of children with invasive aspergillosis died in the hospital, compared with 1% (1736 of 151 537) of similarly immunocompromised children without invasive aspergillosis [3]. Despite substantial achievements over the past 2 decades, diagnosis and treatment of invasive fungal diseases in children and adolescents are still limited by a number of factors. As a matter of fact, not all antifungal agents are approved in the pediatric population, the appropriate dosage of several drugs has not been established for all age groups, and postmarketing data providing information on safety and efficacy of approved agents under real-life circumstances are scant. Similarly, the value of newer diagnostic tools is not defined in the pediatric population, although they are of major impact for establishing preventive and treatment strategies of invasive aspergillosis [4]. Whereas both the halo sign and the air-crescent sign revealed by pulmonary computed tomography scan are common and highly suggestive for invasive mold infection in adult patients and are included as clinical criteria in the revised definitions of invasive fungal disease set forth by the European Organization for Research and Treatment of Cancer and the Mycosis Study Group (EORTC/MSG) [5], radiographic findings in immunocompromised children with proven pulmonary invasive fungal disease are often nonspecific. In younger children (aged <5 years) in particular, typical signs of pulmonary invasive fungal disease are not seen in the majority of patients. In contrast, multiple nodules or fluffy masses and infiltrates that look like mass lesions are frequently reported [2]. Testing galactomannan (GM), a polysaccharide cell-wall component that is released by all Aspergillus spp. during cell growth, has been evaluated in multiple studies in adults and is included as a microbiological criterion in the revised definitions of invasive fungal disease by the EORTC/MSG consensus group and in a number of Editorial Commentary

Invasive aspergillosis in patients with liver disease

Invasive aspergillosis (IA) has been traditionally considered an infection occurring in patients with well established risk factors, such as neutropenia, hematologic malignancies, organ transplantation, or HIV. However there is increasing evidence that apparently immunocompetent patients, such as those with severe liver disease, are also at high risk for Aspergillus infections. Here we report two cases of proven invasive aspergillosis and review 72 others of aspergillosis reported since 1973 in patients with liver disease. Most patients had end-stage cirrhosis or acute hepatic failure. Overall mortality rate was 72.2% and the majority of patients who died had CNS involvement, disseminated infections, and received antifungal agents on a less common basis. A trend toward higher survival for cases reported during the period 2000-2009 was observed. Literature data suggest that invasive aspergillosis is a potential fatal complication of severe liver disease. The high mortality rate observed in these patients appears to be related not only to the severity of their underlying conditions, but also to a lack in clinical diagnosis. New diagnostic tools, e.g., galactomannan (GM) antigen test, in association with increased clinical suspicion may allow an early diagnosis and improve the outcome of IA in this particular category of patients.

Positive Result of the Aspergillus Galactomannan Antigen Assay Using Bronchoalveolar Lavage Fluid from a Patient with an Invasive Infection Due to Lichtheimia ramosa

Positive galactomannan antigen (GM) test results with serum by the Platelia Aspergillus assay (Bio-Rad, Marnes-La-Coquette, France) have been reported to occur during invasive fungal infections caused by Penicillium marneffei ([8][1]), Cryptococcus neoformans ([2][2]), Geotrichum capitatum ([3][3

血液病棟における侵襲性アスペルギルス症サーベイランス

Invasive aspergillosis (IA) is a major cause of morbidity and mortality among the immunocompromised, especially those undergoing hematopoietic stem cell transplantation. With spore inhalation the usual infection route, such subjects must be protected from environmental spore contamination, necessitating measures such as high-efficiency particulate air (HEPA) filtration. In April 2006, we implemented a new transplantation unit with HEPA filtration. We retrospectively evaluated its efficacy for hospitalized transplantation unit subjects whose sera were tested for aspergillus galactomannan antigen between April 2004 and March 2007. Subjects numbered 265 (973 samples) categorized as definite, probable, or possible. The earliest IA onset date was when symptoms, positive radiological findings, or positive galactomannan antigen tests occurred, based on revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions. We classified cases when IA occurred over 10 days after admission as hospital-acquired. No such cases were detected after November 2005 and IA incidence decreased significantly after the new unit began being used. Results suggest that the new unit and HEPA filtration helped eliminate nosocomial IA.

Low Sensitivity of the (1-3)-Beta-D-Glucan Assay for Diagnosis of Invasive Aspergillosis in Hematologic Malignancy Patients.

Abstract 2242Poster Board II-219Invasive aspergillosis (IA) is a common opportunistic infection in hematologic malignancy patients. The diagnosis of IA is difficult and the outcome is poor despite recent progress in treatment. The detection of galactomannan antigen is useful in diagnosis of IA and is defined as one of EORTC/MSG diagnostic criteria. The (1-3)-beta-D-glucan assay is also used in diagnosis of invasive fungal disease, but the sensitivity and specificity of these tests for IA are variable in recent reports. To evaluate the correlation of them, we analyzed retrospectively the results of these tests in IA cases of hematologic malignancy patients.From January 2006 to December 2008, we reviewed 2914 hematologic malignancy patients (AML=492, ALL=198, MDS=284, NHL=1373, HL=92, MM=375) retrospectively who were recieved chemotherapy or stem cell transplantation(SCT). 607 cases received SCT are included in this study. We diagnosed IA according to the EORTC/MSG criteria, and extracted the data of galactomannan antigen and (1-3)-beta-D-glucan assay examined at diagnosis of each case.43 cases(1.5%) are diagnosed as invasive fungal disease (Aspergillus=24, Candida=9, Mucor=6, Trichosporon=2, Cryptococcus=1, Geotrichum=1). 23 IA cases are analyzed (proven: 3 cases, probable: 20 cases). All cases are positive for galactomannan antigen test(range, 0.5-5.0< ODI, cut-off value:0.5), but only 9 cases for (1-3)-beta-D-glucan assay (range, 24.5-313pg/ml, cut-off value:20). In the three cases of proven IA, only one case are positive for this assay. There is no difference in patient characteristic and prognosis between the positive and negative group.We conclude that the (1-3)-beta-D-glucan assay is not useful tool for diagnosis of invasive aspergillosis. Disclosures:No relevant conflicts of interest to declare.

Comparison of Aspergillus galactomannan antigen testing with a new cut‐off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis

The usefulness of two tests in the serodiagnosis of chronic pulmonary aspergillosis (CPA) was compared. The tests were the serum Aspergillus galactomannan antigen test (Platelia (R) Aspergillus) by enzyme-linked immunoassay (EIA) using old and new cut-off indexes, and the Aspergillus precipitating antibody test. Both Aspergillus-precipitating antibody and Platelia Aspergillus EIA positivity were measured in the sera of 28 patients at the time of diagnosis of CPA. Serum Aspergillus precipitating antibody positivity was 89.3% (25/28) in CPA patients. Serum Platelia Aspergillus EIA positivity was 21.4% (6/28) using the old cut-off index (> or =1.5) and 50% (14/28) using the new cut-off index (> or =0.5)-still less than that for Aspergillus precipitating antibody. Three of the 28 CPA patients had positive reactions in the Platelia Aspergillus EIA using the old cut-off index but not in the Aspergillus precipitating antibody test. Positivity for (1,3) beta-d glucan was 15.4%, and that for culture on CHROMagar Candida was 17.9%. One patient with pulmonary actinomycosis had a false-positive reaction in the Platelia Aspergillus test with the new cut-off index. For the diagnosis of CPA, Aspergillus precipitating antibody testing is more sensitive than the Platelia Aspergillus EIA, even with the new cut-off index. False-positive reactions are observed with the Platelia Aspergillus EIA in patients with conditions such as pulmonary actinomycosis. Results should be interpreted with care when patients are positive for the Platelia Aspergillus EIA but negative for Aspergillus precipitating antibody.

Insidious sinusitis leading to catastrophic cerebral aspergillosis in transplant recipients

Cerebral aspergillosis is an important cause of mortality in organ transplant recipients and is typically associated with concomitant pulmonary infection.1 Herein we describe two patients with insidious Aspergillus sinusitis leading to catastrophic CNS infection. ### Case reports. #### Patient 1. A 56-year-old man with pancreas and kidney transplant was transferred to our tertiary care facility with meningoencephalitis and cerebral infarction. He had a history of new onset headache of 6 weeks with fever. His immunosuppressive regimen consisted of mycophenolate mofetil, prednisone, and tacrolimus with prophylactic sulfamethoxazole/trimethoprim and valganciclovir. He had a temperature of 38.9 °C, opened eyes to voice only but followed commands, and neurologic examination showed neck stiffness, dysarthria, right-sided anisocoria, and a left sided hemiparesis. Empiric antimicrobial therapy was started, including fluconazole. CT showed fluid and membrane thickening within paranasal sinuses. Cranial MRI demonstrated enhancement involving the basilar meninges and sphenoid sinus (figure, A). Diffusion-weighted images demonstrated restricted diffusion in the right pons, right cerebellum, and right caudate head consistent with acute infarction (figure, B). Cerebral angiogram demonstrated narrowing of arteries around the basal cisterns and occlusion of the right superior cerebellar artery, consistent with vasculitis secondary to basal meningitis. Lumbar puncture (LP) revealed CSF leukocytes of 1,200/mm3 (94% neutrophils), protein of 73 g/L, and glucose of 64 mg/dL. Fluconazole was changed to voriconazole. Cultures of CSF remained negative. The serum galactomannan antigen test was normal (0.39 index), …

Correlation between high-resolution computed tomography and galactomannan antigenemia in adult hematologic patients at risk for invasive aspergillosis

Objectives 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). Material and methods 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. Results 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 ≥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 ≥1.5. 20 patients were diagnosed of angioinvasive IA from which 80% had a GM level ≥1.5. Conclusion 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.

Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients.

During recent years, a rising incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic critically ill patients has been reported. Critically ill patients are prone to develop disturbances in immunoregulation during their stay in the ICU, which render them more vulnerable for fungal infections. Risk factors such as chronic obstructive pulmonary disease (COPD), prolonged use of steroids, advanced liver disease, chronic renal replacement therapy, near-drowning and diabetes mellitus have been described. Diagnosis of IPA may be difficult and obtaining histo- or cytopathological demonstration of the fungus in order to meet the gold standard for IPA is not always feasible in these patients. Laboratory markers used as a non-invasive diagnostic tool, such as the galactomannan antigen test (GM), 1,3-β-glucan, and Aspergillus PCR, show varying results. Antifungal therapy might be considered in patients with persistent pulmonary infection who exhibit risk factors together with positive cultures or sequentially positive GM and Aspergillus PCR in serum, in whom voriconazole is the drug of choice. The benefit of combination antifungal therapy lacks sufficient evidence so far, but this treatment might be considered in patients with breakthrough infections or refractory disease.

Prospective Aspergillus Galactomannan Antigen Testing in Pediatric Hematopoietic Stem Cell Transplant Recipients

The galactomannan (GM) assay is an approved noninvasive test for detection of invasive aspergillosis (IA) that has been validated in adult patients with hematologic malignancies who are undergoing bone marrow transplantation. There have been few studies with this assay in pediatric patients, but early reports suggest that there may be differences in the performance such that false-positive GM tests in pediatric patients are more common than in adult patients. We performed a prospective study in pediatric hematopoietic stem cell transplant recipients with twice-weekly sampling for GM detection during the highest risk periods of neutropenia and graft-versus-host disease. We analyzed 826 serum samples from 64 patients, including 15 serum samples from one patient diagnosed with probable IA according to defined criteria. Twenty of 811 samples tested positive on repeat testing (specificity, 97.5%; 95% CI: 96.2-98.4%) including samples from 8 of 63 patients without clinical evidence of IA according to study criteria (specificity, 87.3%; 95% CI: 76.9-93.4%). Eleven patients received piperacillin/tazobactam therapy, and 4 of the 11 patients had a positive assay result coinciding with the dates of piperacillin/tazobactam administration. When samples from these patients were excluded, specificity increased to 98.4% (95% CI: 97.2-99.1%) by sample and to 91.5% (95% CI: 81.6-96.3%) by patient. The GM assay holds promise for early, noninvasive diagnosis of IA in high-risk children and false-positive results were not common or unexplainable. This study supports further validation of this assay in a large-scale, pediatric-dedicated format.