Head-to-Head Comparison of Inhibitory and Fungicidal Activities of Fluconazole, Itraconazole, Voriconazole, Posaconazole, and Isavuconazole against Clinical Isolates of Trichosporon asahii

Abstract

Treatment of disseminatedTrichosporon infections still remains difficult. Amphotericin B frequently displays inadequate fungicidal activity and echinocandins have no meaningful antifungal effect against this genus. Triazoles are currently the drugs of choice for the treatment of Trichosporon infections. This study evaluates the inhibitory and fungicidal activities of five triazoles against 90 clinical isolates of Trichosporon asahii. MICs (g/ml) were determined according to Clinical and Laboratory Standards Institute microdilution method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest concentrations that inhibited ϳ50 and 100% of growth, respectively). Minimum fungicidal concentrations (MFCs; g/ml) were determined by seeding 100 l of all clear MIC wells (using an inoculum of 10 4 CFU/ml) onto Sabouraud dextrose agar. Time-kill curves were assayed against four clinical T. asahii isolates and the T. asahii ATCC 201110 strain. The MIC-2 (ϳ50% reduction in turbidity compared to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that inhibited 90% of isolates at 48 h were, respectively, 8/32/64 g/ml for fluconazole, 1/2/8 g/ml for itraconazole, 0.12/0.5/2 g/ml for voriconazole, 0.5/2/4 g/ml for posaconazole, and 0.25/1/4 g/ml for isavuconazole. The MIC-0 endpoints yielded more consistent MIC results, which remained mostly unchanged when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and are easier to interpret. Based on the time-kill experiments, none of the drugs reached the fungicidal endpoint (99.9% killing), killing activity being shown but at concentrations not reached in serum. Statistical analysis revealed that killing rates are dose and antifungal dependent. The lowest concentration at which killing activity begins was for voriconazole, and the highest was for fluconazole. These results suggest that azoles display fungistatic activity and lack fungicidal effect against T. asahii. By rank order, the most active triazole is voriconazole, followed by itraconazole ϳ posaconazole ϳ isavuconazole > fluconazole.

Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

“…The minimal fungicidal concentration (MFC) values for the C 12 and C 14 TOB analogues were determined as previously described (19,20) with minor modifications. To determine MFCs, yeast cells of 1 ϫ 10 4 CFU/ml were used to perform broth microdilution assays as described above.…”

Comparision of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF MS) with API ID 32C and VITEK 2 for the identification of Trichosporon species

“…Trichosporon asahii Türkiye dâhil birçok ülkede en sık izole edilen Trichosporon türüdür (20)(21)(22)(23) . Bu türün birçok antifungale karşı yüksek MİK değerlerine sahip olması özellikle daha sık izole edildiği immunsupresif ve yenidoğan hasta grubunda sorun oluşturmaktadır (20) .…”

“…Ülkemizde yapılan bir çalışmada, bu türün amfoterisin B, flukonazol ve 5-flusitozine düşük duyarlı olduğu ve vorikonazolün en aktif antifungal olduğu belirtilmiştir (23) . Mantar tedavisinde sıklıkla kullanılan bu antifungallere karşı duyarlılığının düşük olması, bu türün hızlı ve doğru olarak tanımlanmasının tedaviyi yönlendirmede önem taşıdığını göstermektedir (21)(22)(23) . …”

Infection Due to Non-Candidal Yeasts

“…Although not yet approved, isavuconazole also shows significant in vitro activity against most strains of Trichosporon (Table 9.4) [25]. In fact, it appears to have better activity than fluconazole [25].…”