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Antifungal agents are available in systemic and/or topical formulations. The choice of antifungal agent(s) and duration of therapy depend not only on the causative pathogen but also the anatomic location and severity of the infection and host immune status. For example, topical antifungal agents are less likely to cause toxicity and should, as a rule, be the first choice for treating skin and mucous membrane infections, whereas tinea capitis and onychomycosis (fungal infection of the nails) are best treated systemically (see Chapter 362). Infections that are severe, are disseminated, or involve the bloodstream should be treated with systemic therapy. In some instances, aggressive initial therapy using more potent antifungal agents with higher toxicity profiles may be warranted as initial therapy for life-threatening invasive fungal diseases in immunocompromised hosts. This aggressive initial therapy may be followed by less aggressive “step-down” therapy until immune reconstitution occurs. It is not uncommon that drug-drug interactions (eg, azole agents with anticancer chemotherapies) limit antifungal options in practice. To guarantee the maximum effectiveness and safety, therapeutic drug monitoring (TDM) is essential, especially for some of the systemic azole agents and flucytosine. In contrast to antibacterial therapy, correlation between in vitro susceptibility test results (eg, minimal inhibitory concentrations [MICs]) and clinical outcome has not been established for each antifungal-pathogen combination except for fluconazole, voriconazole, and echinocandins with Candida species. Organism- and disease-specific antifungal therapies are summarized in Table 242-1.
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