Optimizing antifungal choice and administration

Background: The antifungal armamentarium includes a number of drug classes and agents within each class. Successful IFI management depends on optimal matching of drug choice with the individual patient and causative pathogen, and maximizing effectiveness of the selected drug through appropriate dosing and toxicity management. Objective: This review is intended to provide a brief overview of key factors involved in optimizing antifungal choice and administration for patients with invasive fungal infections (IFIs). Findings: Antifungals differ in spectrum of activity, and these differences are critical when selecting the antifungal most likely to provide success for a patient with an IFI. When the species has not yet been identified, an analysis of regional epidemiology and risk factors can provide clues as to the most likely pathogen. For severely immunocompromised patients, a fungicidal agent may be preferred over a fungistatic agent, although more research is needed in this area. Triazoles, particularly itraconazole and posaconazole, exhibit great interpatient pharmacokinetic variability related to absorption. Steps can be taken to maximize absorption when using these agents. Voriconazole concentration is affected by polymorphisms in the major metabolic enzyme, cytochrome P450 2C19. Triazoles, and to a lesser extent other antifungals, are also subject to drug-drug interactions, which needs to be considered when selecting a particular antifungal agent for use in a severely ill patient on polypharmacy. Therapeutic drug monitoring may be a useful adjunct for patients receiving itraconazole, voriconazole, or posaconazole. When the IFI involves a pharmacologically protected site, such as the central nervous system (CNS) or eye, 5-fluorocytosine, fluconazole, or voriconazole are generally preferred. Echinocandin penetration is typically inadequate for IFIs of the CNS or eye. Antifungal agents also differ in their toxicity profiles, and these issues also need to be considered and managed when making an antifungal choice. Conclusion: Successful management of IFIs relies in part on the accurate selection of an antifungal agent for the infection. Drug characteristics can help in the selection of drug therapy. These characteristics include the drug's spectrum of activity, pharmacokinetics, pharmacodynamics, toxicity profile, and distribution to the infection site. Matching the drug profile to the patient and fungal species contribute to optimal management of infection.