Abstract
We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Here, we compare the performance of MS-DS for the diagnosis of IC, invasive aspergillosis (IA), and mucormycosis (MM) with those of commercially available antigen detection tests. This retrospective study included 48 patients (23 IC patients [74 serum samples], 15 IA patients [40 serum samples], and 10 MM patients [15 serum samples]) and 49 appropriate controls (102 serum samples). MS-DS, mannan (Mnn), galactomannan (GM), and (1,3)-β-d-glucan (BDG) were detected by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS, Platelia, and Fungitell assays, respectively. For IC, the sensitivity and specificity of the MS-DS index, BDG detection, and Mnn detection were 62% and 84%, 82% and 60%, and 33% and 94% per serum sample and 83% and 69%, 96% and 31%, and 39% and 86% per patient, respectively. For IA, the corresponding values in comparison to BDG and GM detection were 83% and 81%, 62% and 95%, and 62% and 100% per serum sample and 93% and 76%, 87% and 90%, and 93% and 100% per patient, respectively. Nine of the 10 MM patients had a positive MS-DS result. MS-DS gave an early diagnosis in IC (73% positivity before blood culture), IA (positive before GM detection in six patients), and MM (positivity mainly preceded the date of diagnosis) patients. For IC, persisting MS-DS was associated with a poor prognosis. The different biomarkers were rarely detected simultaneously, suggesting different kinetics of release and clearance. For IA, MS-DS provided better complementation to GM monitoring than BDG monitoring. MS-DS detects panfungal molecules circulating during invasive fungal infections. The performance of MS-DS compared favorably with those of biological tests currently recommended for monitoring at-risk patients. Further validation of this test in multicenter studies is required.
Highlights
Invasive candidiasis (IC) and invasive aspergillosis (IA) are major life-threatening nosocomial invasive fungal infections (IFIs) [1,2,3]
The principle of the MALDItime of flight (TOF) mass spectrometry (MS) procedure as well as the methodology used for the serological diagnosis of invasive candidiasis (IC) were described previously [16]
In such a complex setting, the 100% specificity achieved by referring to healthy blood donors as controls is not relevant; in this pilot study, special care was taken to include the most appropriate control groups, which consisted of hospitalized patients at high risk of IFI
Summary
Invasive candidiasis (IC) and invasive aspergillosis (IA) are major life-threatening nosocomial invasive fungal infections (IFIs) [1,2,3]. Difficulties in the biological detection of IFIs are related to the low yield of culture-based methods [8]; blood cultures are positive in only ϳ50% of episodes of IC and in anecdotic cases of IA To fill this gap, methods have been developed for the detection of fungal molecules in sera from patients [9,10,11]. There is extensive literature on the diagnostic value of fungal polysaccharide detection, including [1,3]--D-glucan (BDG) [12], present in Candida and Aspergillus cell walls, and mannan (Mnn) or galactomannan (GM), found in Candida and Aspergillus, respectively Each of these assays, which present different compromises between sensitivity and specificity, are currently widely used, there is a lack of consensus about therapeutic decisions based on the results of these tests in the complex setting of IC and IA [13,14,15]. (This work was presented as an oral communication at the 26th European Congress of Clinical Microbiology and Infectious Diseases, Amsterdam, Netherlands, 9 to 12 April 2016.)
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