T2Candida Diagnostic Test for ICU Patients at Risk for Invasive Candidiasis

Although the diagnostic performance for all tests were modest in regards to the detection of invasive candidiasis in patients in a high-risk intensive care unit (ICU), the combination of the new test T2Candida and blood culture seemed to have the best performance, according to a study published in Open Forum Infectious Diseases.

Blood culture is the gold standard test for invasive candidiasis, comprising candidemia and deep-seated candidiasis, but the sensitivity of this test is low. The average time to blood culture positivity is approximately 2 days, and some studies have associated a 2-day antifungal therapy delay with a more than doubled mortality rate. There is, therefore, a need for rapid diagnostic testing in invasive candidiasis.

Researchers investigated the performance of T2Candida, a new diagnostic test recently approved by the Food and Drug Administration, compared with Candida mannan antigen (MAg), and blood culture for the detection of invasive candidiasis in a study cohort of 126 ICU patients at high risk for invasive candidiasis. Despite 3 days of broad-spectrum antibiotics, the patients still had sepsis. Paired sets of T2Candida, MAg, and blood culture were obtained 2 times per week for a total of 334 sets. Based on a review of patient records, patients were classified into categories of unlikely, possible, likely, or proven invasive candidiasis.

At the time of enrollment, 77% (n=92) of patients were already receiving antifungal therapy (primarily fluconazole 66%). Fifteen patients (11.9%) tested positive by T2Candida (n=11), MAg (n=10), or blood culture (n=4). At inclusion, the T2Candida species distribution was supported by the identification of colonizing isolates or blood culture in 10 of 11 cases (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]). Patients were classified as unlikely (n=98), possible (n=11), likely (n=6), and proven (n=11).

In patients in the category of proven invasive candidiasis, sensitivity was found as 55%, 45%, and 36% for T2Candida, blood culture, and MAg tests, respectively. In patients with proven or likely invasive candidiasis, the sensitivities increased to 59%, 29%, and 41% for T2Candida, blood culture, and Mag test, respectively. The sensitivity increased to 64%-65% when T2 Candida was combined with one of the other tests; whereas when T2Candida was not included, sensitivity decreased to 53%-55%. The negative predictive value for proven vs others, and proven/likely vs others was similar across all tests (94% to 96% and 90% to 95%, respectively). The positive predictive value for T2Candida in proven cases of invasive candidiasis was 50% compared with 36% for MAg testing. Positive predictive value for these tests respectively to 83% compared with 64%, in patients with either proven or likely invasive candidiasis.

Researchers concluded, “T2Candida was the biomarker that contributed the most to improving the diagnostic sensitivity while retaining a good specificity and [negative predictive value]. This makes it a promising addition to the diagnostic armamentarium. However, our study also suggests that maximal benefit of diagnostic efforts may require that sampling is initiated as early as possible, preferably before initiation of antifungal therapy, when the sensitivity and [negative predictive value] of T2Candida and [blood culture] testing are maximal and probably sufficient for excluding [invasive candidiasis].”

This work was supported in part (test kits were provided, and part of the hourly fee for the ICU doctors spent on patient record review was reimbursed to the ICU departments) by T2Biosystems.

Reference

Arendrup MC, Andersen JS, Holten MK, et al. Diagnostic performance of T2Candida among ICU patients with risk factors for invasive candidiasis [published online March 25, 2019]. Open Forum Infect Dis. doi: 10.1093/ofid/ofz136