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Figure 1. Micafungin sodium: an echinocandin class semisynthetic lipopeptide. Reproduced with permission from [3].
(Figure omitted. See article PDF.)
Invasive fungal infections
An invasive fungal infection (IFI) is a severe and, if untreated, fatal disease commonly caused by ubiquitously present fungal organisms. Although there are case reports of fungal infections in otherwise healthy patients, IFI most frequently occur in the immunocompromised patient and/or are caused iatrogenically. The most common pathogens in IFI are Candida spp. and Aspergillus spp.
Candida spp.
Several Candida spp. are commensals of humans and are found on the skin as well as in the gastrointestinal (GI) and female genital tract. A regular infection route for Candida is the GI tract of immunocompromised patients, which allows translocation of colonizing Candida spp. into the bloodstream [1]. Other well-established predisposing factors are the introduction of foreign bodies (catheters and prostheses), GI surgery, systemic antibiotics (increasing colonization of Candida in the GI tract) and immune suppression in general. Candida spp. may cause local infections of the mucous membrane as well as severe infections of single organs (ocular, respiratory tract and CNS candidiasis and Candida endocarditis) and systemic infections (e.g., candidemia and disseminated candidiasis).
Aspergillus spp.
Aspergillus spp. are ubiquitous fungi commonly found in walls and dust. Aspergillus spores are small and easily penetrate deeply into the bronchial system upon inhalation. In neutropenic patients in particular, natural defense mechanisms (alveolar macrophages and neutrophil granulocytes) against Aspergillus fail, facilitating invasive pulmonary aspergillosis (IPA). In the authors' experience, without any antifungal prophylaxis, almost 50% of patients with acute myeloid leukemia develop an IPA during the overall course of their treatment. Other infections caused by Aspergillus spp. are sinusitis, as well as CNS and sometimes soft-tissue infections.
Echinocandins
Echinocandins are the most recent systemically active antifungal treatment options. They are potent inhibitors of 1,3-β-D -glucan synthesis, an integral and critical cell wall component of numerous pathogenic fungi. A common feature of the echinocandin class of antifungals is fungicidal activity against most Candida spp. and fungistatic activity against most Aspergillus spp. All echinocandins currently under investigation are ineffective against most other fungal species, including Cryptococcus spp., Trichosporon spp. and Zygomycetes. There are currently three echinocandins available on the US market. Caspofungin (Cancidas® , Merck & Co., Inc.,...