Antifungal drugs: predicting clinical efficacy with pharmacodynamics

Invasive fungal infections are on the rise, particularly in hospitalized patients and immunocompromised hosts. In recent years, several new antifungals have become available at a rapid pace. Data on pharmacokinetics/pharmacodynamics of the newer/older antifungal drugs are accumulating. As with bacterial infections and antibacterial drugs, predicting the clinical efficacy of antifungal drugs based on pharmacodynamic parameters is becoming feasible. For the echinocandin class, a ratio of 10 or more for peak concentration/minimum inhibitory concentration (MIC) predicts efficacy against most Candida organisms. Increasing the currently used doses does not appear to improve efficacy. For the triazole class, a ratio of 25 or more for the pharmacodynamic parameter, AUC/MIC, predicts efficacy of the antifungal drugs against invasive Candida infections. More data are needed for invasive mold infections. The polyene class of drugs exhibit concentration-dependent activity; doses higher than those used conventionally do not show any clinical advantage. Monitoring serum levels of the newer triazoles, voriconazole and posaconazole, appears to be necessary in clinical practice to ensure efficacy and avoid toxicity. Flucytosine levels help to predict toxicity, but not efficacy. Other classes of drugs do not warrant monitoring serum concentrations. As invasive fungal infections usually occur in the setting of compromised immune defenses, clinical success does not depend upon the activity of the drugs alone; host immune factors need consideration to predict clinical outcome.