Diagnostic Performance of T2Candida Among ICU Patients With Risk Factors for Invasive Candidiasis

Abstract

Background Invasive candidiasis (IC) comprises candidemia and deep-seated candidiasis. Blood culture (BC) is the gold standard test, but sensitivity is low. T2Candida is a new diagnostic test. We investigated the performance of T2Candida, BC, and Candida mannan antigen (MAg) for detection of IC in a high-risk intensive care unit (ICU) population. Methods One-hundred twenty-six ICU patients at high risk of IC with sepsis despite 3 days of broad-spectrum antibiotics were included. Paired BC, T2Candida, and MAg were obtained twice weekly (334 sets). Patients were classified into proven, likely, possible, or unlikely IC based on patient record review. Results At enrollment, 92 (77%) patients were receiving antifungal therapy (mainly fluconazole 66%). Fifteen (11.9%) patients were positive by BC (n = 4), T2Candida (n = 11), or MAg (n = 10). The T2Candida species distribution at inclusion (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]) was supported by the identification of BC or colonizing isolates in 10/11 cases. Patients were classified with proven (11), likely (6), possible (11), and unlikely (98) IC. Defining IC as proven/proven&likely/proven&likely&possible, respectively, the sensitivity was as follows: T2Candida (55%/59%/39%), BC (45%/29%/ 8%), and MAg (36%/41%/32%). The negative predictive value was similar across the tests for proven vs others and proven/likely vs others (94%–96% and 90%–95%, respectively). For test combinations including T2Candida, the sensitivity increased to 64%–65%, without hampering the positive predictive value. Conclusions In conclusion, although the diagnostic performance was modest for all the tests, the combination of T2Candida and BC seemed to have the best diagnostic performance, and thus implementation of T2Candida may improve the diagnosis of IC.

Diagnostic Performance of a Novel Multiplex PCR Assay for Candidemia among ICU Patients

“…Direct comparison of the diagnostic values with other published methods specific for detection of Candida is complex due to the unique settings of each clinical study. Nevertheless, one recent study assessing the T2Candida approach showed a lower specificity of <60% for high-risk ICU patients compared to data shown here [23]. Another study reported a sensitivity of 43% and a specificity of 94% for the T2 system for a patient cohort receiving empirical antifungal treatment [31].…”

“…This test is based on amplification, hybridization, and detection of pathogen nucleic acids [22]. The T2-System (T2 Biosystems, Lexington, Massachusetts, United States) uses magnetic resonance analysis to confirm candidemia [23]. The advantages of such molecular approaches are the superior sensitivity and the speed compared to culture-based testing [15].…”

Diagnosis and Treatment of Candidemia in the Intensive Care Unit

“…151 In a study conducted in 126 ICU patients at high risk of IC and with sepsis despite 3 days of broad-spectrum antibiotics, the sensitivity and specificity of the T2Candida panel for proven IC were 55 and 93%, respectively, with 50% PPV and 93% NPV. 152 In another study conducted among 46 patients with severe sepsis or septic shock and multiple risk factors for candidemia, the T2Candida panel showed 100% sensitivity (95% CI: 2.5-100), 92% specificity (95% CI: 78-98), 25% PPV (95% 1-81), and 100% NPV (95% CI: 90-100). 153 Of note, some authors have also suggested that a positive T2Candida test could be a potential marker of poor outcome in patients receiving empirical antifungal therapy for suspected IC.…”

Molecular Methods for the Diagnosis of Invasive Candidiasis

“…Arendrup et al recently conducted another prospective study with 126 ICU patients which were classified into groups of proven, likely, possible, or unlikely IC based on the results of BC, culture from sterile sites, colonization, a Candida antigen assay, and clinical findings. Compared with BC and the antigen test, the T2Candida Panel had the highest sensitivity for the detection of IC [ 62 ], even though the sensitivity was lower than observed in the 2015 Mylonakis et al study [ 61 ]. The best sensitivity was achieved by a combination of BC and the T2Candida Panel [ 62 ].…”

“…Compared with BC and the antigen test, the T2Candida Panel had the highest sensitivity for the detection of IC [ 62 ], even though the sensitivity was lower than observed in the 2015 Mylonakis et al study [ 61 ]. The best sensitivity was achieved by a combination of BC and the T2Candida Panel [ 62 ]. As the test also detects non-viable cells, T2MR might be a useful tool for the monitoring of candidemia upon initiation of antifungal therapy.…”