Early Diagnosis of Candidemia in the Intensive Care Unit by Clinical and Molecular Methods: A Prospective...

Early diagnosis and treatment of candidemia in intensive care units (ICUs) remain a significant challenge globally because of the lack of well-established non-culture-based diagnostic methods. This study aimed to evaluate risk factors in critically ill ICU patients, develop a unique Candida score, and create a real-time polymerase chain reaction (PCR) assay for the early diagnosis of candidemia.

The study was conducted in three phases: 1) Retrospective analysis of 100 ICU patients from İstanbul University-Cerrahpaşa between January 2017 and December 2018 to identify risk factors for invasive candidiasis, 2) development of Cerrahpaşa Candida score based on these findings, and 3) prospective evaluation of 75 ICU patients, applying the newly created Cerrahpaşa Candida score and implementing a rapid PCR-based test on whole blood samples. The PCR assay was part of a development study and was not used for scoring or clinical diagnostic evaluation. Specific primer pairs and EvaGreen® dye (Biotium Inc., USA) were used to differentiate between Candida albicans and Candida parapsilosis isolates through melting curve analysis of real-time PCR amplicons. The PCR test demonstrated a detection limit of 10 CFU/mL.

In the retrospective analysis, key risk factors for candidemia were identified, including sepsis, intra-abdominal infections, hospitalization within the last three months, prolonged antibiotic use (>1 week), Candida colonization, percutaneous endoscopic gastrostomy, central venous catheter, and acute kidney injury ( p<0.05). During the prospective phase, which evaluated 75 ICU patients, a Cerrahpaşa Candida score cutoff value of ≥4 points was established as significantly associated with an increased risk of candidemia (p<0.05). The Cerrahpaşa Candida score and PCR assay, targeting the internal transcribed spacer (ITS) and D1/D2 regions, showed clinical utility for early diagnosis.

The Cerrahpaşa Candida score and real-time PCR test developed in this study offer promising tools for guiding antifungal therapy in ICU patients, potentially reducing unnecessary antifungal use. However, improvements in PCR sensitivity are necessary. Further multicenter studies with larger patient cohorts are recommended to validate the clinical effectiveness of these diagnostic tools.