Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations.
New triazole antifungals (voriconazole, posaconazole, ravuconazole and albaconazole) have been developed to meet the increasing need for new antifungals, and address the rising incidence of invasive fungal infections and the emergence of fungal resistance. This report describes the spectrum of activity of the newer-generation triazoles based on data from in vitro, animal and clinical studies. The authors discuss the use of these agents in combination with other antifungals, the extent of cross-resistance, their toxicity profile and pharmacokinetic properties. A total of two agents are currently available: voriconazole (which is becoming a primary treatment for the management of invasive aspergillosis) and posaconazole (which demonstrates a broad antifungal spectrum). A further two agents, albaconazole and ravuconazole, are undergoing early clinical evaluation and their future is uncertain. For all newer triazoles, concerns about emerging drug-resistant fungi and the incidence and management of breakthrough infections will dictate their role in antifungal prophylaxis and treatment.
Aperis
George
G
Harvard Medical School, Massachusetts General Hospital, Division of Infectious Diseases, 55 Fruit Street, Boston, MA 02114-2696, USA.
Mylonakis
Eleftherios
E
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D002177:Candidiasis / Q000188:drug therapy*; D003453:Cryptococcosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D025141:Drug Resistance, Fungal; D004359:Drug Therapy, Combination; D006801:Humans; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D013844:Thiazoles; D014230:Triazoles; C101425:posaconazole; C104066:ER 30346; D065819:Voriconazole