Invasive candidiasis: a review of nonculture-based laboratory diagnostic methods

Invasive candidiasis is a life-threatening complication of critically ill immunocompromised patients with high attributable mortality. Due to non-specific clinical presentation, early detection of candidemia and accurate identification of Candida species are essential pre-requisites for improved therapeutic outcome. Since blood culture-based methods lack sensitivity and species-specific identification by conventional methods is time-consuming, detection of immunological and molecular markers has provided an alternative for early diagnosis of invasive candidiasis. Additionally, serial estimations of these biomarkers have provided opportunities to monitor response to therapy and initiate pre-emptive therapy in suspected patients before clinical signs appear. Antigen-based methods include detection of β-D-glucan, a panfungal marker, and Candida mannan, a genus-specific marker. Although both these markers have moderate sensitivity, they provide a useful adjunct to the diagnosis if performed in select patient population in parallel for exclusion of false positive/negative results. A negative β-D-glucan test on at least two occasions has a high negative predictive value. Concomitant detection of Candida mannan and anti-mannan antibodies has sensitivity of ~70% before blood cultures become positive. Significant advances have also been made in nucleic acid-based detection methods, including a commercial real-time PCR assay (SeptiFast) for detection of five major clinically important Candida spp. in blood specimens within 6 h. Furthermore, matrix-assisted laser desorption ionization time-of-flight mass spectrometry enables species-specific identification of yeast isolates within an hour. While these immunological and molecular tools mark a significant advance towards early and specific diagnosis of candidemia and invasive candidiasis, further evaluation of these approaches in different clinical settings is warranted.