Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections

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). Invasive candidiasis (IC) and invasive aspergillosis (IA) are major life-threatening nosocomial invasive fungal infections (IFIs) (1-3). Although less prevalent, mucormycosis (MM) is an emerging problem. Progress in antifungal therapy has not significantly reduced the high rates of morbidity and mortality associated with IFIs, particularly in intensive care units (ICUs) and oncohematology units (4-6), due to difficulties in obtaining an early diagnosis, an important condition for a favorable outcome (7). 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 (9-11). These methods include the detection of fungal DNA in body fluids and tissues, for which no consensual recommendations have been produced due to the lack of standardization. In contrast, 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, although there is a lack of consensus about therapeutic decisions based on the results of these tests in the complex setting of IC and IA (13-15). For MM, no serological test is currently of diagnostic help.In a previous report, we described the presence of a specific m/z 365 matrix-assisted laser desorption ionization (MALDI) mass spectrometry (

Performance of serum (1,3)‐ß‐d‐glucan screening for the diagnosis of invasive aspergillosis in neutropenic patients with haematological malignancies

“…24 These differences have also been reported for other novel markers, such as serum disaccharide detected with mass spectrometry (MS-DS). 27 Although our study was not primarily designed for assessing the impact of BDG positivity on the prognosis of IA (and thus the analysis was not adjusted for other factors possibly influencing mortality), we observed lower 180-day survival in patients with IA and a positive vs negative BDG. More research with appropriate adjustment is warranted to confirm these findings and enrich our understanding on the possible prognostic role of BDG in patients with IA.…”

“…In this regard, Pazos and colleagues observed that BDG tends to become positive before GM in some patients with IA, probably reflecting the fact that the kinetics of blood release and clearance of different fungal markers is not the same during the course of infection . These differences have also been reported for other novel markers, such as serum disaccharide detected with mass spectrometry (MS‐DS) …”

Fulminant Auricular Mucormycosis in a Diabetic Patient

“…Until this moment, none of the serological tests currently on the market were efficient for the diagnosis. Apparently MS-DS could fill this gap, improving the promptness of a clinical diagnosis of this high lethal condition 11 . In most cases, the infection is rapidly progressive with high risk of death, especially if underlying risk factors (i.e., metabolic acidosis) are not corrected in time 1 .…”

Non-culture based assays for the detection of fungal pathogens

“…Moreover, results of evaluation of this method suggest the possibility of panfungal analyses and diagnosis of IMI for which currently there are no available commercial serological tests that are efficient for the diagnosis. However, it has to be highlighted that this biological test requires further evaluation and validation in multicenter studies [134].…”