Diagnosis of fungal infection: new technologies for the mycology laboratory

Abstract

The dramatic increase in nosocomial invasive mycoses over the past two decades has led to increased interest in the area of antifungal development. Unfortunately, the infusion of new diagnostic technology into the clinical mycology laboratory has lagged behind. Although newer, automated, continuous-monitoring blood culture systems are as sensitive as the older, manual "gold standard" system, the recovery of fungi from blood, as well as other clinical specimens, remains an insensitive marker for invasive fungal infection. Antigen assays for the rapid diagnosis of invasive fungal infections are in development, and galactomannan and glucan are two such promising antigens. Glucan may be present in the blood of patients with infection secondary to a wide variety of fungal pathogens, including Candida, Aspergillus, Fusarium, Saccharomyces, Trichosporon and Acremonium species. Early data suggest galactomannan may be present in the blood in detectable levels very early in the course of invasive aspergillosis. The galactomannan assay currently undergoing evaluations may actually be positive prior to the clinical suspicion for infection and may be useful in monitoring therapeutic response as well; however, the etiology of false-positive results following cytotoxic chemotherapy still has to be elucidated. PCR assays are also being developed in the research laboratory, however, the PCR assays will require a significant amount of adaptation and validation before they are ready for clinical care. Well-planned studies to evaluate the performance characteristics as well as appropriate clinical and cost-effective application of these new tests are needed.

Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients

“…2 Depending on risk factors, the incidence of IFIs in HSCT recipients, in general, ranges between 14 and 25%. 1,3,4 Candida albicans and Aspergillus sp. account for the majority of IFIs, but the emergence of other organisms (eg Scedosporium and Fusarium) has changed the spectrum of the disease.…”

Nonribosomal cyclic peptides: specific markers of fungal infections

“…5,10 Nonspecific X-ray and CT scans are often insensitive, underestimate the extent of disease and fail to alert clinicians to the necessity of urgent surgery in the case of pulmonary aspergillosis. 11 The golden standards in diagnostics still are the recovery of fungi from a tissue or blood, culture and subsequent mycological evaluation.…”

“…14 Immunocompromised patients do not reliably produce antibodies, and the presence of an antibody does not precisely distinguish between colonization and infection. 5 Furthermore, antifungal antibodies are often created by a healthy individual, which also hampers the decision process. So far, research has focused on identifying antigens or metabolites that are detectable in blood or urine.…”

“…The sensitivities of currently available commercial assays for these molecules are 31-90%, 6-71%, ¾50% and 54-75%, respectively. 5,15 None of the assays has performed well enough to be able to recommend its routine use in a clinical laboratory. Higher sensitivity and specificity are obtained in detection of the galactomannan polysaccharide antigen, a cell wall component of Aspergillus, 16 although the high rate of false-positive results has dampened enthusiasm.…”

“…4 The incidence of invasive fungal infections has increased dramatically over the past 20 years. 5 In a three-year (1995-1998) surveillance study of 49 hospitals across the United States, Candida infections were shown to be the 4th leading cause of nosocomial bloodstream infections.…”