Early serum (1→3)‐β‐D‐glucan levels in patients with burn injury

Shupp, Jeffrey W.; Petraitienė, Rūta; Jaskille, Amín D.; Pavlovich, Anna R.; Matt, Sarah E.; Nguyen, Do T.; Kath, Melissa A.; Jeng, James C.; Jordan, Marion H.; Finkelman, Malcolm; Walsh, Thomas J.; Shoham, Shmuel

doi:10.1111/j.1439-0507.2011.02068.x

Cited by 12 publications

(8 citation statements)

References 15 publications

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“…Our ICU patients showed a wide variability in terms of underlying clinical conditions and potential confounders; thus, it could be challenging to firm define the potential causes of reduced specificity. Among these potential factors, only the occurrence of severe burns and/or breakdown of mucosal integrity was independently associated with false‐positive results, confirming the very low PPVs reported in literature for burnt and trauma patients 58,59 . Overall, our data suggest that, in ICU and trauma settings, the added value of BDG quantification by Wako assay is probably more relevant to exclude than to prove IFI.…”

Section: Discussionsupporting

confidence: 82%

Quantification of 1,3‐β‐d‐glucan by Wako β‐glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study

Cento

Alteri

Mancini

et al. 2020

Mycoses

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Summary Objectives Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available β‐d‐Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut‐off values for IFI exclusion. Methods BDG results by Wako β‐glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. Results Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1‐3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut‐offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). Conclusions The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non‐ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

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Section: Discussionsupporting

confidence: 82%

Quantification of 1,3‐β‐d‐glucan by Wako β‐glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study

Cento

Alteri

Mancini

et al. 2020

Mycoses

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“…A 12 h BDG was positive in 8 ⁄ 19 patients and was not related to gauze coverage. 24 Detection BDG in the serum of patients from surgical intensive care unit were reported as a useful tool to aid in the early diagnosis of invasive candidasis, however a sampling interval of 3-4 days post surgery was recommended to allow BDG leached from surgical sponges and gauze to fall to background levels. 25 Racil and collagues 26 reported a high rate of false BDG results in patients at risk for IFI.…”

Section: Discussionmentioning

confidence: 99%

Does ampicillin‐sulbactam cause false positivity of (1,3)‐beta‐D‐glucan assay? A prospective evaluation of 15 patients without invasive fungal infections*

Metan

Agkus

Koç

et al. 2011

Mycoses

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The purpose of this study was to investigate the interaction between intravenous ampicillin-sulbactam treatment and (1,3)-beta-D-glucan (BDG) assay. Fifteen patients with a median age of 60 (16-81) without known risk factors for invasive fungal infections who received a daily dose of 3×2g ampicillin-sulbactam monotherapy from different batches were included in the study. Thirteen patients had soft tissue infections. The 5 of 13 patients who went under surgery had surgical dressings. Serum samples were obtained both before and after antibiotic infusion on the first, third, seventh and tenth days of an ampicillin-sulbactam treatment course. BDG was assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA, USA) according to manufacturers' specifications. All serum samples were also tested for galactomannan (GM) antigenemia by Platelia Aspergillus ELISA (Bio-Rad Laboratories, Marnes-la-Coquette, France). A total of 37 of 117 serum samples were positive for BDG at a threshold of 80pg ml(-1) . Seven of 37 BDG positive serum samples had a GM index ≥0.5. When a cutoff value of ≥0.5 was used for GM positivity, 16 (13.3%) serum samples were positive. For a cutoff value of ≥0.7, eight (6.6%) serum samples were positive. There were no statistically significant differences in the median BDG levels (P=0.47) or median GM indices (P =0.28) of the various sampling times. None of the SAM vials tested positive for BDG or GM. After ruling out fungal infections and all known potential causes of false BDG positivity, environmental contamination remained possible cause of BDG reactivity. We did not observe any significant association of ampicillin-sulbactam administration and positive assays for BDG or GM.

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“…One study suggested that BG is undetectable in normal CSF (11). False-positive test results occur in serum assays in association with a number of conditions (12)(13)(14). We do not yet know whether CSF false positives would occur due to biologic variables in the CSF or from other events in sample processing such as the use of cotton gauze or a cotton alcohol swab to clean the puncture site in the LP procedure, but these cases illustrate an association between detectable results and suspected disease.…”

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confidence: 99%

Cerebrospinal Fluid (1,3)-β- d -Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis

et al. 2013

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f This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-␤-D-glucan in cerebrospinal fluid during the current U.S. outbreak of fungal meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.(1,3)-␤-D-glucan (BG) is found in cell walls of multiple fungi. Its detection in serum assists in diagnosis of invasive fungal infections (1). Recently, diagnostic challenge has arisen in the fungal meningitis outbreak associated with exposure to contaminated epidural steroid injections (2). Diagnosis in this setting has been established by culture of cerebrospinal fluid (CSF) and/or detection using a pan-fungal PCR assay performed by the Centers for Disease Control (CDC). However, these tests have not always been positive in suspected cases (3). One early study has demonstrated the proof of concept of using CSF BG detection in diagnosis of fungal central nervous system infection in an experimental hematogenous Candida meningoencephalitis model (4). Here we report our experience with CSF BG measurement in 5 individuals from Johns Hopkins Hospital and Indiana University Hospital who were exposed to potentially contaminated drugs. Cases were diagnosed and managed according to CDC guidelines. BG was tested at Beacon Diagnostics Laboratory (East Falmouth, MA) using the Fungitell assay. Information was obtained by chart review with approval from the Johns Hopkins Institutional Review Board.The first case was a 55-year-old woman who developed headaches, blurred vision, and injection site pain 1 week after lumbar epidural injection with potentially contaminated methylprednisolone and was admitted 35 days after symptom onset when the outbreak was recognized. CSF showed 30 white blood cells (WBCs)/mm 3 and normal glucose and protein; no opening pressure was recorded. Intravenous voriconazole was initiated, but symptoms continued despite troughs of 2 to 3 g/ml. Repeat lumbar puncture (LP) showed opening pressure of 42 cm H 2 O, 974 WBC/mm 3 (56% neutrophils, 16% lymphocytes, 21% monocytes), 1,000 red blood cells (RBCs)/mm 3 , normal glucose, and 93 mg/dl protein, with a negative culture. CSF PCR performed by the CDC was negative. With serial LPs for persistent headache and elevated opening pressures and voriconazole increase to maintain troughs of 3 to 5 g/ml, her symptoms resolved. CSF fungal cultures from postinjection days 57, 69, and 73 were negative. CSF BG samples sent on postinjection days 57 and 73 were positive at 2,396 and 701 pg/ml, respectively (Table 1).The second case was a 37-year-old man who underwent lumbar epidural injection with potentially contaminated methylprednisolone and developed a headache several days later. Thirteen days after the injection he started oral voriconazole. His symptoms did not improve, and LP 2 weeks later showed 5 WBCs/mm 3 ( Table 1). PCR performed by the CDC and fungal cultures were negative. Magnetic resonance imaging (MRI) of the brain showed a small intrapa...

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Early serum (1→3)‐β‐D‐glucan levels in patients with burn injury

Cited by 12 publications

References 15 publications

Quantification of 1,3‐β‐d‐glucan by Wako β‐glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study

Quantification of 1,3‐β‐d‐glucan by Wako β‐glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study

Does ampicillin‐sulbactam cause false positivity of (1,3)‐beta‐D‐glucan assay? A prospective evaluation of 15 patients without invasive fungal infections*

Cerebrospinal Fluid (1,3)-β- d -Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis

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