Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations

被引:69
作者
Aperis, George [1 ]
Mylonakis, Eleftherios [1 ]
机构
[1] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
关键词
albaconazole; aspergillosis; Aspergillus spp; Candida spp; candidaemia; candidiasis; coccidioidomycosis; cryptococcal meningitis; fusariosis; histoplasmosis; posaconazole; ravuconazole; scedosporiasis; UK-109; 496; UR-9825; voriconazole; zygomycosis;
D O I
10.1517/13543784.15.6.579
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 proper-ties. 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.
引用
收藏
页码:579 / 602
页数:24
相关论文
共 173 条
[41]   Evaluation of broth microdilution testing parameters and agar diffusion Etest procedure for testing susceptibilities of Aspergillus spp. to caspofungin acetate (MK-0991) [J].
Espinel-Ingroff, A .
JOURNAL OF CLINICAL MICROBIOLOGY, 2003, 41 (01) :403-409
[42]   In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens [J].
Espinel-Ingroff, A .
JOURNAL OF CLINICAL MICROBIOLOGY, 1998, 36 (01) :198-202
[43]   Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts [J].
Espinel-Ingroff, A .
JOURNAL OF CLINICAL MICROBIOLOGY, 1998, 36 (10) :2950-2956
[44]  
Espinel-Ingroff Ana, 2003, Revista Iberoamericana de Micologia, V20, P121
[45]   Oral bioavailability of posaconazole in fasted healthy subjects - Comparison between three regimens and basis for clinical dosage recommendations [J].
Ezzet, F ;
Wexler, D ;
Courtney, R ;
Krishna, G ;
Lim, J ;
Laughlin, M .
CLINICAL PHARMACOKINETICS, 2005, 44 (02) :211-220
[46]  
Fung-Tomc JC, 1998, ANTIMICROB AGENTS CH, V42, P313
[47]   Breakthrough Candida infections in patients receiving voriconazole [J].
Gerzenshtein, L ;
Patel, SM ;
Scarsi, KK ;
Postelnick, MJ ;
Flaherty, JP .
ANNALS OF PHARMACOTHERAPY, 2005, 39 (7-8) :1342-1345
[48]   Antifungal activity of voriconazole (UK-109,496), fluconazole and amphotericin B against hematogenous Candida krusei infection in neutropenic guinea pig model [J].
Ghannoum, MA ;
Okogbule-Wonodi, I ;
Bhat, N ;
Sanati, H .
JOURNAL OF CHEMOTHERAPY, 1999, 11 (01) :34-39
[49]  
GILMAN AL, 2005, PEDIAT BLOOD CANC
[50]   Susceptibility profile of 29 clinical isolates of Rhodotorula spp. and literature review [J].
Gomez-Lopez, A ;
Mellado, E ;
Rodriguez-Tudela, JL ;
Cuenca-Estrella, M .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2005, 55 (03) :312-316