Invasive candidiasis as a disease spectrum includes not only candidemia (with or without deep-seated infection), but also isolated deep-seated candidiasis without candidemia [5]. Deep-seated Candida infection is difficult to study because it includes a heterogenous group of conditions ranging from direct local inoculation (e.g., Candida peritonitis in peritoneal dialysis, spinal infection from contaminated steroid injections), to hematogenous metastatic seeding of Candida sp. (e.g., infective endocarditis, hematogenous fungal endophthalmitis) [22]. Intra-abdominal candidiasis (IAC) usually refers to peritonitis and abdominal abscess in patients with recent abdominal surgery, anastomotic leak, or gastrointestinal perforation [22,23,24].

The usefulness of positive T2Candida results despite negative blood cultures for the identification of IAC has been noted in a few cases. These included patients with IAC and positive T2Candida result concordant with Candida sp. isolated from cultures of peritoneal fluid, infected bile16, and explanted liver tissue [25]. Building on these preliminary case reports, a 2019 ICU study examined T2Candida performance in a real-world patient population with suspected invasive candidiasis including IAC [26]. Blood cultures, T2Candida, and Candida Mannan antigen (MAg) were performed on 126 ICU patients at high-risk for invasive candidiasis with sepsis despite 3 days of empiric broad-spectrum antibiotics. Paired samples were obtained twice weekly (334 sets) and patients were classified as having proven, likely, or possible invasive candidiasis based on culture results, imaging, and expert review [26]. At enrollment, 77% were on antifungal therapy. In all, 28 of 126 (22%) had proven, likely, or possible invasive candidiasis and IAC was the most common manifestation in 57% of these cases. Five of the 11 proven cases had Candida sp. isolated on blood cultures and T2Candida detected all except a C. kefyr that is not included on the panel. Overall, the sensitivity of T2Candida, blood culture and MAg in proven cases of invasive candidiasis was 55%, 45% and 36% [26]. The addition of T2Candida to blood culture or MAg resulted in the best diagnostic performance. All three tests had negative predictive value of >90% [26]. A later study compared T2Candida with blood cultures and cultures from deep-seated infection [27]. In total, 133 samples were taken from 32 patients with candidemia and 22 patients with deep-seated invasive culture proven candidiasis. T2Candida was positive in 27% of the patients with deep-seated invasive candidiasis [27]. Of note, only 88% patients with candidemia had positive T2Candida result at any time point, which is lower than rates reported in the early clinical trials [27]. Lastly, a 2020 study compared performance of T2Candida to BDG and blood cultures for the diagnosis IAC [28]. Patients were enrolled if they were at risk for IAC based on recent gastrointestinal tract perforation, necrotizing pancreatitis, or abdominal surgery as well as concurrent Candida colonization from a nonsterile site. Of 48 patients enrolled, 38% had proven IAC defined as Candida isolated by perioperative intra-abdominal culture [28]. In patients with proven IAC, blood cultures and T2Candida were positive in 11% and 33%, respectively [28]. Two patients had IAC with species not included on the T2Candida panel (C. kefyr and C. lusitaniae) [28]. Overall, T2Candida sensitivity/specificity were 33%/93% and PPV/NPV 71%/74% for diagnosing IAC. The above studies provide limited data that T2Candida may serve as a surrogate marker for deep-seated candidiasis and IAC, especially in cases with negative blood cultures or when invasive procedures cannot be performed to obtain specimens for testing from deep-seated sites of infection.