Therapeutic drug monitoring for antifungal triazoles: pharmacologic background and current status

Invasive fungal infections are important causes of morbidity and mortality in critically ill and immunocompromised patients. Since these infections remain difficult to diagnose and can be rapidly fatal, appropriate antifungal therapy is key to successful prevention, management, and survival. The introduction of antifungal triazoles in the 1990s was a major breakthrough in antifungal chemotherapy and has revolutionized prevention and treatment over the ensuing decades: Fluconazole and itraconazole were the first viable alternatives to standard treatment with amphotericin B deoxycholate and assumed an important role in systemic antifungal prophylaxis in high-risk patient populations. A decade later, voriconazole became the first-line option for treatment of invasive aspergillosis, yielding improved response rates and overall survival relative to amphotericin B deoxycholate. Around the same time, posaconazole was developed as a highly effective prophylactic agent, reducing invasive fungal infections in comparison to fluconazole or itraconazole, and improving overall outcome of treated patients. Finally, the recent introduction of isavuconazole has provided an equally effective alternative to voriconazole in treatment of invasive aspergillosis with an additional indication for treatment of mucormycosis.