Molecular Diagnosis of Yeast Infections

Abstract

Purpose of Review The use of molecular tests to aid the diagnosis of invasive yeast infection, in particular invasive candidosis, has been described for over two decades, yet widespread application is limited, and diagnosis remains heavily dependent on classical microbiology. This article will review developments from the past decade in attempt to build on existing knowledge. It will highlight clinical performance and limitations while reviewing developments on recognized procedures; it will also provide insight into novel approaches incorporated in response to clinical demand (e.g. C. auris and antifungal resistance) or technological advances (e.g. next-generation sequencing). Recent Findings Limited methodological standardization and, until recently, unavailability of commercial options have hindered the integration of molecular diagnostics for yeasts. The development of certain, novel commercial methods has received considerable evaluation allowing a greater understanding of individual assay performance, but widespread multicentre evaluation of most commercial kits is lacking. The detection of emerging pathogens (e.g. C. auris ) has been enhanced by the development of molecular tests. Molecular methods are providing a better understanding of the mycobiome, mechanisms of resistance and epidemiology/phylogeny. Summary Despite over two decades of use, the incorporation of molecular methods to enhance the diagnosis of yeast infections remains limited to certain specialist centres. While the development of commercial tests will provide stimulus for broader application, further validation and reduced costs are required. Over the same period of time, Aspergillus PCR has become more widely accepted driven by international efforts to standardize methodology; it is critical that yeast PCR follows suit. Next-generation sequencing will provide significant information on the mycobiome, antifungal resistance mechanism and even broad-range detection directly from the specimen, which may be critical for the molecular detection of yeasts other than Candida species, which is currently limited.

Serologic biomarkers in Candida and Aspergillus infections of the central nervous system: A comparison of galactomannan, mannan and β‐1,3‐D‐gucan testing from serum and cerebrospinal fluid

“…Nineteen patients with CNS specimens growing Candida 14 or Aspergillus fumigatus 5 were included in this study (Table 1). Despite recovery of Candida from CNS specimens, four patients did not meet the criteria for a proven invasive fungal infection (IFI) according to the EORTC/MSG consensus criteria, 12 since there were no clinical or radiological abnormalities consistent with an infectious disease process.…”

“…Classic microbiological techniques like microscopy and culture perform poorly in the setting of CNS IFI, for example culture positivity in CNS aspergillosis was reported to be as low as 9–24% 3,7–9 . Molecular methods like PCR have also not fulfilled the hopes placed in them to date 13,14 . Contrarily, antigen testing is a well‐established tool for diagnosis of IFI and can be performed from an easily available specimen, that is serum 11,15 …”

“…3,[7][8][9] Molecular methods like PCR have also not fulfilled the hopes placed in them to date. 13,14 Contrarily, antigen testing is a well-established tool for diagnosis of IFI and can be performed from an easily available specimen, that is serum. For combined MAN/anti-Candida-antibody testing, the sensitivity was 71%.…”

Novel Chromogenic Medium CHROMagarTM Candida Plus for Detection of Candida auris and Other Candida Species from Surveillance and Environmental Samples: A Multicenter Study

“…Early diagnosis is key for the successful treatment of fungal infections, and more rapid and reliable tests are needed [ 34 , 35 ]. Non-culture-based methods, such as PCR, are rapid methods to diagnose yeast infections, although their use in clinical laboratories is still low, especially in resource-limited settings [ 36 ]. Chromogenic media are a valuable alternative in resource-limited settings due to their lower costs and ease of use, allowing a rapid presumptive identification of the main clinical Candida species [ 20 ].…”

Performance of existing clinical scores and laboratory tests for the diagnosis of invasive candidiasis in critically ill, nonneutropenic, adult patients: A systematic review with qualitative evidence synthesis

“…However, it is of note that the number of studies on the use of PCR for the diagnosis of IFD is steadily increasing over the years; thus, it is likely that further evidence to more accurately delineate the positioning of molecular methods within diagnostic algorithms for IC in critically ill patients will become available in the near future. [50][51][52][53][54][55][56][57][58][59] Another limitation of the present review is that, owing to the heterogeneity of the available studies, no meta-analysis for diagnostic tests accuracy could be performed. This in fact underlines once again the relevance of the FUNDICU project: once common definitions of IFD in critically ill patients in ICU will be adopted, design and implementation of such studies will be easier, and combination of results will provide more reliable estimates.…”