Evaluation of Quantitative Differences of Classic Methods, Fungal Biomarkers, and T2Candida for Assessing the Central Venous Catheter Origin of Candidemia

Background This study was conducted to investigate the diagnostic value of fungal biomarker differentials and T2Candida polymerase chain reaction (PCR) from catheter and peripheral blood samples and to re-evaluate classical conservative methods, such as differential time to positivity of blood cultures (BCs), for the early identification of catheter-related candidemia (CRC) before catheter removal. Methods This prospective study was conducted (March 2023–April 2025) in 2 tertiary hospitals in Spain and Italy. Adults (aged ≥18 years) with candidemia and a central venous catheter in place at diagnosis were included, provided catheter removal occurred within 48 hours of index BC positivity. CRC was defined in patients with candidemia who showed 1 or 2 of the following criteria in the catheter tip: (1) ≥ 15 CFU/plate (Maki technique) or ≥ 1000 CFU/mL (sonication) and (2) any Candida growth on the catheter tip. Blood samples were collected from peripheral veins and catheter lumens to compare the differentials of 1,3-β-D-glucan (BDG), Candida albicans germ tube antibodies, mannan antigen, antimannan antibody, and T2Candida PCR results. Diagnostic metrics were calculated for each test. Results Of 179 episodes of candidemia reviewed, 28 (15.6%) met the inclusion criteria (13 in Spain, 15 in Italy). CRC was confirmed in 11 patients (39.3%) using criterion 1 and in 15 patients (53.6%) using criterion 2. BDG differentials (any difference) demonstrated the highest diagnostic accuracy as follows: sensitivity 81.82%, specificity 82.35%, positive predictive value 75.00%, negative predictive value 87.50%, and overall accuracy 82.14% (criterion 1). However, stricter BDG thresholds (≥20 or ≥30 pg/mL) and the application of criterion 2 reduced the sensitivity. Other biomarkers and T2Candida PCR demonstrated low sensitivity (0%–40%) and variable specificity (25%–100%), with overall accuracies of <64%. Differential time to positivity of BCs yielded a sensitivity of 72.73% and a specificity of 52.94%, with limited accuracy. Conclusions None of the investigated methods achieved sufficient accuracy to diagnose CRC without catheter removal. Despite the limited sample size, this study emphasizes the limitations of current diagnostic approaches and the need for novel tools for reliable noninvasive identification of CRC.