Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Kevin      Watt; Paolo      Manzoni; Michael      Cohen-Wolkowiez; Stefano      Rizzollo; Elena      Boano; Evelyne      Jacqz-Aigrain; Daniel      K. Benjamin

Abstract

Invasive fungal infections in infants admitted to the neonatal intensive care unit are common and often fatal. The mainstay of therapy against invasive fungal infections is antifungal agents. Over the last two decades, the development and approval of these drugs evolved tremendously, and the azole class emerged as important agents in the treatment and prevention of invasive fungal infections. Among the azoles, fluconazole has been used extensively due to its favorable pharmacokinetics, excellent activity against Candida spp, and safety profile. This drug has been well studied in children, but data for its use in infants are largely limited to Candida prophylaxis studies. Voriconazole, a second generation triazole, has excellent activity against Candida and Aspergillus spp. However, data on its use in neonates are extremely limited. Posaconazole and ravuconazole are the newest agents of the triazole family. The antimicrobial spectrum of posaconazole is similar to voriconazole, but with additional activity against zygomycetes. Experience with posaconazole in children is very limited, and there are no reports of its use in infants. Ravuconazole is not approved for use by the FDA, but studies in animals and humans show that it is often fungicidal and has favorable pharmacokinetics. In conclusion, the management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

Keywords: Antifungal agents, triazole, prematurity, infection, candida, aspergillosis, Fluconazole, Voriconazole, Posaconazole, Ravuconazole, Bacterial infections, Neonatal blood, C. krusei