Diagnosis of invasive candidiasis in neutropenic children with cancer by determination of D-arabinitol/L-arabinitol ratios in urine

Christensson, Bértil; Wiebe, Thomas; Pehrson, Christina; Larsson, Lennart

doi:10.1128/jcm.35.3.636-640.1997

Cited by 54 publications

(31 citation statements)

References 19 publications

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“…However, a raised level of (1+3)-P-D-glucan in serum does not provide any clue as to the species involved. Measurement of the fungal metabolite D-arabinitol in urine has been found useful for detection of invasive candidiasis in neutropenic patients (7,8). Analysis of multiple samples seems to be important for patients suffering from postoperative candidiasis (1 7).…”

Section: Discussionmentioning

confidence: 99%

Detection and identification of fungi in blood using broad‐range 28S rDNA PCR amplification and species‐specific hybridisation

Evertsson

Monstein

Johansson

2000

APMIS

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The aim of the present study was to develop a PCR-based method to detect and identify fungi directly from human venous blood. We used broad-range PCR primers that targeted a part of the large subunit 28S rRNA genes. To obtain species-specific hybridisation probes, type strains of Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and Cryptococcus neoformans were PCR amplified, and the amplicons were analysed by gene sequencing. Based on the sequence analysis, species-specific probes that targeted variable regions were designed and used in hybridisation analyses. Between 2 to 10 fungal cells/ml of spiked blood samples could be detected and correctly identified to species. We applied the technique to blood samples obtained from two patients with or two patients without verified candidaemia. The three samples of candidaemia patients were correctly identified to species level, and those of the negative patients remained negative. This method is a potential tool for diagnosis of systemic invasive candidiasis.

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Section: Discussionmentioning

confidence: 99%

Detection and identification of fungi in blood using broad‐range 28S rDNA PCR amplification and species‐specific hybridisation

Evertsson

Monstein

Johansson

2000

APMIS

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“…Moreover, arabinitol ratios were increased in 52-68% of neutropenic patients with cancer undergoing empiric antifungal therapy [13,14]. This has been interpreted to result from an increasing fungal load during long-lasting neutropenia, and arabinitol tests have accordingly been found to be positive 1-2 weeks before first positive blood culture or onset of empiric therapy [13,14]. These observations are confirmed here, where 3/4 neutropenic haematological candidaemia patients showed increased DA/LA ratios in contrast to only 0/2 non-neutropenic haematological patients and 7/18 non-haematological patients with invasive candidiasis.…”

Section: Discussionmentioning

confidence: 99%

Detection of candidaemia in patients with and without underlying haematological disease

Arendrup

Bergmann

Larsson

et al. 2010

Clinical Microbiology and Infection

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Diagnosing candidaemia remains difficult despite the development of new diagnostics. We report a direct comparison of three different blood-culture systems and four indirect tests. One hundred and fourteen episodes either with haematological disease and fever despite antibacterials, or with documented invasive candidiasis, were enrolled prospectively. Clinical, para-clinical information and surveillance cultures were obtained. Blood culture was performed using conventional blood-culture bottles, mycosis bottles, and the Isolator 10 lysis centrifugation system. Serum D-arabinitol/L-arabinitol (DA/LA) ratios were determined by gas chromatography mass spectrometry. Antigen, mannan-antigen (Ag) and anti-mannan antibody (Ab) were detected by CandTec, Platelia Candida Ag ELISA and Candida AB/AC/AK kits, respectively. Episodes were classified as proven (n = 24), probable (n = 14), possible (n = 52) or unlikely (n = 24) invasive candidiasis. Candidaemia involved C. albicans (17), C. albicans + C. glabrata (3), C. tropicalis (1) and yeast (1). Mycosis bottles yielded two additional positives and the conventional blood culture yielded one positive not identified by other blood-culture methods. Considering proven and unlikely episodes, respectively, sensitivity and specificity were as follows: mannan-Ag and/or anti-mannan Ab: 83.3%, 78.3%; DA/LA ratio: 41.7%, 86.4%; and CandTec Candida Ag: 66.6%, 70.8%. Lowering the cut-off values to mannan-Ag 0.10 ng/mL and anti-mannan Ab 4 AU/mL, the values were: 100%, 73.9%. Applying the DA/LA ratio to only patients with haematological neutropenia the values were: 75%, 90.5%. Fungal blood culture allowed slightly improved detection of candidaemia. The best indirect test performance was obtained from combined mannan-Ag and anti-mannan Ab detection, especially with lower cut-offs. DA/LA ratio appears to be useful in the context of haematological neutropenia.

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“…Many medically important species of Candida (including C. albicans, C. tropicalis, and C. parapsilosis) produce measurable amounts of D-arabinitol in culture as well as in infected animals and humans (3,4,5,18). It has been shown elsewhere that patients with invasive candidiasis had higher serum D-arabinitol levels than did uninfected controls and that these levels declined with effective therapy (2,4,19).…”

Section: Discussionmentioning

confidence: 99%

A Rapid, Automated Enzymatic Fluorometric Assay for Determination of d -Arabinitol in Serum

Yeo

Zhang

Schafer³

et al. 2000

J Clin Microbiol

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A rapid enzymatic fluorometric assay for measuringd-arabinitol in serum was developed using recombinantd-arabinitol dehydrogenase from Candida albicans (rArDH). rArDH was produced in Escherichia coli and purified by dye-ligand affinity chromatography. rArDH was highly specific for d-arabinitol, cross-reacting only with xylitol (4.9%) among all polyols tested. A Cobas Fara II centrifugal autoanalyzer (Roche) was used to measure NADH fluorometrically when rArDH and NAD were added to serum extracts, andd-arabinitol concentrations were calculated from standard curves derived from pooled human serum containing known amounts ofd-arabinitol. The method was precise (mean intra-assay coefficients of variation [CVs], 0.8%, and mean interassay CVs, 1.6%) and rapid (3.5 min per assay) and showed excellent recovery of added d-arabinitol in serum (mean recovery rate, 101%). The mean and median d-arabinitol/creatinine ratios were 2.74 and 2.23 μM/mg/dl, respectively, for the 11 patients with candidemia compared to 1.14 and 1.23 μM/mg/dl, respectively, for 10 healthy controls (P < 0.01). These results confirm earlier studies showing that serum d-arabinitol measurement may help to promptly diagnose invasive candidiasis. The technique shows a significant improvement in terms of accuracy, cost, simplicity, specificity, and speed compared with gas chromatography, mass spectrometry, and earlier enzymatic assays.

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Diagnosis of invasive candidiasis in neutropenic children with cancer by determination of D-arabinitol/L-arabinitol ratios in urine

Cited by 54 publications

References 19 publications

Detection and identification of fungi in blood using broad‐range 28S rDNA PCR amplification and species‐specific hybridisation

Detection and identification of fungi in blood using broad‐range 28S rDNA PCR amplification and species‐specific hybridisation

Detection of candidaemia in patients with and without underlying haematological disease

A Rapid, Automated Enzymatic Fluorometric Assay for Determination of d -Arabinitol in Serum

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