Point-Counterpoint: β-
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            -Glucan Testing Is Important for Diagnosis of Invasive Fungal Infections

Theel, Elitza S.; Doern, Christopher D.

doi:10.1128/jcm.01737-13

Cited by 181 publications

(137 citation statements)

References 34 publications

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“…␤-Glucan is stable, and slow clearance from the CSF compartment may occur in coccidioidal meningitis. The lack of correlation with the organism burden and response to therapy is in contrast with the experience with Candida meningitis in rabbits (19), cryptococcal meningitis in humans (16), pediatric central nervous system infections (12), and serum ␤-glucan results in other clinical mycoses (15). However, the serum ␤-glucan value and even its early kinetics did not correlate with outcomes in other mycoses in some studies (20).…”

Section: Discussioncontrasting

confidence: 42%

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

et al. 2016

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c Diagnosing coccidioidal meningitis (CM) can be problematic owing to its infrequency and/or a delay in the positivity of a cerebrospinal fluid (CSF) culture or CSF antibody, particularly if the primary coccidioidal infection is unrecognized. We tested 37 CSF specimens, 26 from patients with confirmed CM and 11 from patients with suspected microbial meningitis without fungal diagnosis, for (1,3)-beta-glucan (BG). BG in CM CSF specimens ranged from 18 to 3,300 pg/ml and in controls ranged from <3.9 to 103 pg/ml. Diagnostic performance was determined using a 31-pg/ml cutoff (the bottom of the serum range according to the directions for the commercial kit, although further serial dilutions of the standard indicated linearity to 3.9). Sensitivity was 96%, specificity was 82%, positive and negative predictive values were 93% and 90%, and the area under the receiver operating characteristic curve was 0.937. Fifteen of 15 samples of >103 pg/ml were CM. The one false-negative specimen was from a patient with a pseudosyrinx, without inflammatory evidence of meningitis activity. Serial samples from some patients were positive at <8 years, indicating no loss of positivity with chronicity. Samples stored frozen since 2000 included those with 2 of the 3 highest values, indicating that fresh samples not required. A previous study indicated serum sensitivities of 53% in acute, 50% in resolved, and 83% in disseminated and meningeal coccidioidomycosis. Three studies of other fungal meningitides ranged from 86 to 1,524 pg/ml CSF, with 37 controls of <4 to 115 pg/ml CSF. CSF BG analysis had good diagnostic performance in CM. CSF BG testing can be useful in CM, and a commercial kit is available. It will be of interest to correlate this with course, treatment, outcome, inflammation, and antigen. The only mycoses with common central nervous system (CNS) involvement are cryptococcal and coccidioidal, so CSF BG screening can be useful in meningitis diagnosis. C occidiodal meningitis, the most feared complication of coccidioidomycosis, has a documented mortality if untreated of 90% in 1 year and 100% in 2 years. It is estimated that there are 200 to 500 new cases per year. It is a granulomatous meningitis, usually involving the basilar meninges. The spinal cord is often involved. It may have an acute, a subacute, or a chronic type of presentation. It may be accompanied by parenchymal abscesses. Complications include hydrocephalus, cerebral infarction, vasculitis, arachnoiditis, cranial nerve palsy, syringomyelia, transverse myelitis, cord compression, seizures, and hyponatremia owing to inappropriate antidiuretic hormone secretion (1).Definitive diagnosis rests on isolating Coccidioides from cerebrospinal fluid (CSF) or other central nervous system (CNS) specimens, although results are only positive in about one-third of patients. A presumptive diagnosis has classically been made by identifying anticoccidioidal antibodies in the CSF; however, antibody results may be negative early in the disease, and false-positive results can occur wit...

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Section: Discussioncontrasting

confidence: 42%

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

et al. 2016

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“…This low sensitivity might indicate a problem with false-negative results, due to the heterogeneity of the 24 IFD cases diagnosed (14 cases of invasive candidiasis, 5 of aspergillosis, 3 of cryptococcal meningitis, and 1 of Pneumocystis pneumonia) over a period of 1 year. Although the infections detected by the BG assay include all fungal infections, BG levels will usually be low or absent in patients with Cryptococcus infections (24). In order to estimate the sensitivity of the BG assay in our study, we used the samples obtained after the first week and only found six episodes of invasive candidiasis without any other invasive fungal infection (IFI).…”

Section: Discussionmentioning

confidence: 99%

Contribution of (1,3)-Beta- d -Glucan to Diagnosis of Invasive Candidiasis after Liver Transplantation

et al. 2015

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bInvasive candidiasis (IC) causes high morbidity and mortality rates after liver transplantation, in part due to delayed diagnosis. The fungal cell wall component (1,3)-beta-D-glucan (BG) could be an early biomarker of IC. This preliminary prospective study was designed to evaluate the contribution of BG measurements to the diagnosis of IC after liver transplantation. All consecutive patients who underwent liver transplantation at Henri Mondor Hospital in France between January and June 2013 were enrolled prospectively in the study. They were monitored weekly for colonization by Candida, and colonization index values were calculated. Serum samples were tested for BG (Fungitell; Cape Cod Inc.) at least weekly between liver transplantation and discharge from the hospital. A total of 52 patients (including 39 male patients) were enrolled, with a median age of 55 years (range, 31 to 69 years). The median Model for End-Stage Liver Disease (MELD) score was 27 (range, 6 to 40). Cultures from 42 patients (81%) yielded Candida spp., with the most common Candida species isolated being Candida glabrata (47%). Six cases of documented IC were found for four of the 52 patients. On the day the clinical diagnosis of IC was made, analysis based on combining two sequential BG-positive samples (>146 pg/ml) and a colonization index of >0.5 revealed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) results of 83%, 89%, 50%, and 97.6%, respectively. The detection of BG associated with Candida colonization may be a promising tool based on a high NPV that can rule out IC among high-risk patients. Liver transplant recipients are at relatively high risk of developing invasive fungal disease (IFD) (1-4). The most common invasive fungal pathogens are Candida spp., followed by Aspergillus spp. (1, 5, 6). Such infections develop in 5% to 10% of transplant recipients and are a major cause of postoperative morbidity and death (4,(7)(8)(9). This is related in part to delayed or missed diagnoses because of the low sensitivity and specificity of the diagnostic tests currently available (1, 10, 11). A serological diagnostic method, i.e., quantification of (1,3)-beta-D-glucan (BG), was recently recommended in the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines on the detection of candidemia in adults (12). BG is a cell wall constituent found in many pathogenic fungi, including Candida, Aspergillus, and Pneumocystis, and it can be detected in patient sera during invasive disease caused by these fungi. In a meta-analysis, Karageorgopoulos et al. showed that BG detection displayed good sensitivity and specificity for the diagnosis of IFD in the general population (13). In the setting of invasive candidiasis (IC), the detection sensitivity of BG ranged from 64% to 100% (14-16). However, the BG assay has not been assessed extensively in populations with solid organ transplants. One study evaluated a preemptive strategy that involved the use of BG monitoring to enable the ...

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“…Clinical signs and symptoms of IFD are often nonspecific; hence, screening strategies with non-culture-based assays, such as BDG screening, can be useful for early diagnosis of infection (12). BDG is included as a mycological criterion in the revised definitions for IFD by the EORTC/MSG consensus group (4), and BDG testing has a BII recommendation for adults with hematological malignancies and HSCT recipients (13).…”

Section: Discussionmentioning

confidence: 99%

β- d -Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2015

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While the assessment of ␤-D-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (<30%). Receiver operating characteristic analyses suggested an optimal cutoff between 60 and 70 pg/ml for different definitions of the onset of IFD. Our data show that BDG screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness. Despite improved supportive care strategies, the morbidity and mortality caused by invasive fungal disease (IFD) are still unacceptably high in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (1). Early diagnosis of IFD is usually difficult, in particular in patients suffering from mold infections, but, on the other hand, early initiation of therapy correlates with better outcome (2, 3). Significant advances in the early detection of IFD have been made with the development of serum tests for fungal antigens, such as galactomannan (GM) or (1¡3)-␤-D-glucan (BDG). Both biomarkers have been included as microbiological criteria in the revised definitions for IFD by the European Organization for Research and Treatment of Cancer/ Mycosis Study Group (EORTC/MSG) consensus group (4), and FDA-approved assays are commercially available for the detection of these fungal antigens. Whereas the cell wall polysaccharide component GM is released by all Aspergillus species and can be detected in patients with invasive aspergillosis (IA), BDG can be detected in patients with IFD due to Aspergillus and Candida spp., Fusarium, Trichosporon, or Saccharomyces, and Pneumocystis jirovecii but also in various bacterial infections and even in healthy individuals (5). A number of factors, such as the concomitant administration of various antibiotic compounds, may result in false positivity, whereas systemic mold-active prophylaxis may increase the number of false-negative results (6, 7).Since GM data in children favorably compare with the results of a meta-analysis for GM testing in adults (8), prospective monitoring of GM levels twice weekly in ...

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Point-Counterpoint: β- d -Glucan Testing Is Important for Diagnosis of Invasive Fungal Infections

Abstract: POINT

Cited by 181 publications

References 34 publications

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

Contribution of (1,3)-Beta- d -Glucan to Diagnosis of Invasive Candidiasis after Liver Transplantation

β- d -Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

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