Fungi, mainly Candida and Aspergillus, have emerged as important
causes of infections in immunocompromised and critically ill patients.
Risk factors for and clinical presentation of invasive mycoses are not
specific. Microbiological documentation is often possible only at an
advanced stage (dissemination, sepsis syndrome) and late antifungal
therapy results in high failure rates (severe complications, mortality).
Antifungal prophylaxis and empirical therapy for persistent fever in
high risk patients are attractive approaches to prevent or early treat
invasive mycoses, respectively. However, they result in the exposure
of large numbers of individuals to antifungal agents, with increased
toxicity, risk of emergence of resistant species and costs. These aspects
highlight the importance of promptly identifying patients who need
antifungal therapy. Conventional culture techniques lack sensitivity
(blood) or specificity (non-blood sites). The colonization by Candida is
a major risk factor: the colonization index based on the amount of
Candida isolated at multiple body sites predicts the risk of invasive
candidiasis. However, a prospective screening of large number of
patients is work-intensive, expensive, and difficult to perform.
Invasive tissue sampling is often difficult to obtain and yield after
prolonged therapy is low. The EORTC-MSG diagnostic classification of
invasive mycoses in immunocompromised patients based on clinical,
microbiological and radiological criteria does not apply to other types
of patients. Thus, diagnosis of systemic fungal infections remains a
major challenge. Computerized imaging techniques have contributed
to expand the diagnostic armamentarium: early diagnosis of invasive
mycoses can be based on characteristics, location, and timing of
radiological lesions. The need for sensitive and specific diagnostic
tools has led to intensive research on detection of fungal metabolites,
antigens, antibodies and DNA. Blood tests for measurement of
circulating antigens such as mannan, galactomannan and
beta-glucan, major components of the fungal cell wall, and of antimannan
antibodies have been developed. Clinical studies have
reported interesting results on their diagnostic performance and have
suggested that these assays may be useful for early diagnosis and
assessment of response to antifungal therapy. Issues such as choice of
the cut-off values, number of positive samples, need for sequential
measurements, false-negative results during antifungal prophylaxis or
therapy, false-positive results in patients receiving synthetic penicillins
and combination of various tests may influence the diagnostic yield.
Some of these markers have been integrated in the updated EORTCMSG
diagnostic classification of invasive mycoses. Variable results
have been reported with home-made molecular methods for detection
of fungal DNA in blood or tissues: lack of standardization, automation,
and inter-laboratory reproducibility has limited their implementation.
New standardized molecular techniques might overcome these
difficulties. In summary, non-invasive tools contribute to early
diagnosis of invasive mycoses. Prospective interventional clinical
studies will evaluate their impact on efficacy, safety and costeffectiveness
of targeted pre-emptive antifungal strategies in patients
at high risk of invasive mycoses.