Editorial [Hot Topic: Fungal Infections and Antifungal Strategies (Guest Editor: Karin Thevissen)]

The current review issue regarding 'Fungal Infections and Antifungal Strategies' unites reviews regarding (i) the infection process of pathogenic fungi resulting in topical or systemic infections, (ii) fungal biofilms, (iii) currently used antimycotics, (iv) novel antifungal drug targets, (v) antifungal susceptibility testing methods and (vi) the use of radiolabeled antifungal agents for early detection of fungal infections. Fungal infections are categorized in two groups: topical and systemic infections. Topical fungal infections affect body surfaces and can be chronic, as discussed by Borgers and coworkers. Systemic fungal infections can occur in an organ or in the whole body and are transferred via the bloodstream. Compared to other microbial infections, systemic fungal infections are characterized by lower frequencies but generally high mortality rates (40-100%). The most common causes of these infections are Candida spp., as discussed by Mavor and coworkers, and filamentous fungi such as Aspergillus spp., as discussed by Brakhage. Several factors are associated with the increasing incidence of fungal infections, including the larger population of immunocompromized patients and the increasing use of invasive devices and implants that can be colonized by fungal biofilms. Biofilms are crucial for the development of fungal infections as they can serve as a nidus for disease. Moreover, surface attachment causes these fungal cells to enter a special physiological state in which they are highly resistant to most of the currently used antifungal drugs, as discussed by Chandra and coworkers. Since there are no fungal vaccines currently licensed, the only clinical recourse to combat fungal infections is the use of therapeutics. The currently used antifungal therapeutics are prone to resistance and suffer from pharmacological limitations, harmful drug-drug interactions, limited activity spectrum and/or high general cytotoxicity, as discussed by Francois and coworkers. Therefore, the search for new antifungal components with a novel mode of action is imperative. Recent advances in genetics and genome-based technologies will allow for the identification and validation of new antifungal drug targets to design novel target-based screening strategies, as discussed by Tournu and coworkers and Thevissen and coworkers. To drive this antifungal drug discovery process more efficiently, novel in vitro assays that mimic in vivo fungal growth, thereby more accurately predicting in vivo efficacy of antifungal components, are mandatory. Current in vitro susceptibility tests will be discussed by Pfaller. An accurate and rapid diagnosis is a critical factor limiting efficient antifungal therapy in immunocompromized patients. Therefore, fast and localized diagnosis of a broad range of pathogenic fungi is mandatory to efficiently combat fungal infections. Given the limitations of the currently used PCR- and ELISA-based methods, development of newer diagnostic techniques are mandatory. A promising novel diagnostic technique is the use of radiolabeled antifungals to monitor the in vivo distribution of fungal infections in infected hosts by Single Photon Emission Computerized Tomography or Positron Emission Tomography, as discussed by Lupetti and coworkers. In conclusion, it can be stated that the following developments are needed to tackle the increasing problem of systemic fungal infections and the lack of efficient antifungal therapeutics: (i) the identification of novel types of antifungal components with respect to their mode of action and fungal targets, (ii) improved in vitro susceptibility testing methods and animal models to more accurately evaluate in vivo efficacy of these novel antifungals, and (iii) early and reliable detection and localization of fungal infections in order to efficiently target antifungal therapy.