In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts

Abstract

The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC 50 and MIC 90 values for posaconazole were 0.063 g/ml and 1 g/ml, respectively. MIC 90 values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 g/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.

Combined antifungal approach for the treatment of invasive mucormycosis in patients with hematologic diseases: a report from the SEIFEM and FUNGISCOPE registries

“…Livio Pagano, 1 Oliver A. Cornely, 2,3 Alessandro Busca, 4 Morena Caira, 1 Simone Cesaro, 5 Cristiana Gasbarrino, 6 Corrado Girmenia, 7 Werner J. Heinz, 8 Raoul Herbrecht, 9 Cornelia Lass-Flörl, 10 Annamaria Nosari, 11 Leonardo Potenza, 12 Zdenek Racil, 13 1-2011-2012).…”

“…[1][2][3] Among the available antifungals, amphotericin B (AmB) formulations and posaconazole demonstrate the most promising in vitro activities against Mucorales, 4,5 and their combination displays synergistic in vitro activity. 6,7 However, pre-clinical studies in neutropenic and diabetic ketoacidotic mice with IM reported no improvement in survival under a combination of posaconazole and liposomal amphotericin B (LAmB), compared to L-AmB monotherapy.…”

Use of posaconazole in the treatment of infective rhinocerebral mucormycosis

“…12,16 However, in contrast to previous azole antifungals such as fluconazole and voriconazole, it also demonstrates enhanced in vitro activity against mucorales. 10 However, there are concerns about achieving reliable therapeutic levels in vivo to treat mucormycosis.…”

Role of posaconazole in the treatment of oropharyngeal candidiasis

“…26 Another study by Sabatelli et al compared the activity of posaconazole with itraconazole, fluconazole, voriconazole, and amphotericin B against 19,000 strains of yeasts and molds. 9 Posaconazole was more active than, or within 1 dilution of, the comparator drugs against 7000 isolates of Candida and Cryptococcus species. Also, posaconazole was active against species of Candida and Aspergillus which showed resistance to fluconazole, voriconazole, and amphotericin B, and was much more active than other triazoles against Zygomycetes.…”

“…11 Posaconazole has good activity against Candida species that are less susceptible to fluconazole (eg, C. krusei, C. guilliermondii, and C. dublinensis), but is less active against C. glabrata. 9 Based on MIC 90 values, posaconazole was found to be more potent than fluconazole and equal or more potent than itraconazole, voriconazole, and amphotericin B against these isolates.…”