There are 46,000 estimated cases of invasive candidiasis diagnosed each year in the U.S. [1]. Recent multicenter surveillance studies estimate that invasive candidiasis represents about 6% of all hospital-acquired infections and candidemia, the most common form of invasive candidiasis, ranks second among healthcare associated bloodstream infections after Staphylococcus aureus [1]. Candidemia is associated with a high mortality rate that can exceed 60% in cases of septic shock [2]. Timely initiation of antifungal therapy and source control are predictors of favorable outcomes [2,3].

Blood cultures have historically been considered the gold standard for diagnosis of candidemia and are the only method that allows for susceptibilities testing of Candida spp., and as such remain an essential component of all diagnostic algorithms. However, the slow turn-around time of blood cultures, and the decrease of their sensitivity in the presence of antifungal agents [4], such as among immunocompromised hosts on antifungal prophylaxis, highlight the need for nonculture diagnostic tests as adjuncts to blood cultures for the timely diagnosis of candidemia [5].

1, 3-beta-D-glucan (BDG) testing (Fungitell; Associates of Cape Cod, East Falmouth, MA, USA) has been used as a biomarker for the diagnosis of invasive candidiasis and the results of this assay in serum have been included in the mycological criteria for the diagnosis of invasive fungal infections proposed by the EORTC and Mycoses Study Group that were last revised in 2008 [6]. BDG is present in the cell wall of many fungi including Candida spp. The performance of the assay in the literature varies based on the patient population it is used, the pretest probability of invasive fungal infection in the individual patient, as well as the criteria used to define a positive result (i.e., threshold for positivity, single vs multiple consecutive positive results) [7]. However, the lack of specificity of this assay for Candida spp. infections, and the high false positivity rate in patients receiving albumin, intravenous immunoglobulin, systemic antimicrobials etc. [8–10] question the utility of incorporating this assay in diagnostic strategies for candidemia especially in the light of newer molecular diagnostic assays, such as the T2Candida assay (T2 Biosystems, Lexington, MA) [11], [12], [13].

The T2Candida panel is a fully automated qualitative assay that combines nuclear magnetic resonance and PCR molecular assays to directly detect and identify 5 different Candida spp., namely C. albicans, C. glabrata, C. parapsilosis, C. tropicalis and C. krusei, from whole blood samples. Candida cells are lysed by mechanical bead beating and Candida DNA is amplified using a thermostable polymerase (T2Biosystems, Inc) and pan-Candida primers for the intervening transcribed spacer 2 region of the Candida ribosomal DNA operon [13,14]. Species-specific capture probes then hybridize within the pan-Candida amplicons and lead to Candida spp. speciation. The amplified product is detected with the assistance of supramagnetic nanoparticles by amplicon-inducted agglomeration that changes the sample's T2MR signal. The initial analysis of the performance of the technology in artificially supplemented blood samples by Neely et al. did show a significant change in time to diagnosis compared to blood cultures with a 98% positive agreement and 100% negative agreement with the BACTEC blood culture system [14]. The clinical performance of the assay was further validated in 2 multicenter clinical trials, the DIRECT1 and DIRECT2 clinical trials [15,16]. In these studies, the T2Candida assay was found to have an overall sensitivity of 99.1% and 89.0% and a specificity of 99.4% and 98.1%, respectively.

In this study, we aim to evaluate the 2 clinical practices followed in our hospitals for the diagnosis of candidemia among hospitalized patients and examine the consistency with which a positive or a negative result influences antifungal prescribing, as well as compare overall antifungal utilization and patients’ outcomes among patients tested with each 1 of these practices. Practice#1 includes a combination of blood cultures and T2Candida panel, and practice#2 includes a combination of blood cultures, T2Candida panel and Beta-D-glucan (BDG),