The Role of Isavuconazonium Sulphate for the Treatment of Blastomycosis: A Case Series and Antifungal Susceptibility

Abstract

Background Blastomyces spp, the etiologic agents of blastomycosis, are endemic dimorphic fungi that require prolonged antifungal therapy, which can be complicated by adverse drug effects. Isavuconazonium sulphate (ISA) is a triazole with in vitro and in vivo activity against Blastomyces spp, but there is a paucity of clinical data supporting its use for treatment of blastomycosis. Methods This retrospective case series identified 14 patients with blastomycosis at least partially treated with ISA at the University of Wisconsin between 2015 and 2019. Treatment duration and outcomes were documented. In addition, 29 clinical isolates of Blastomyces spp between 2004 and 2017 were tested for minimum inhibitory concentrations against ISA and other antifungals. Results Fourteen patients were treated with a median of 255 days of ISA accounting for 68% of total therapy. Half (7 of 14) of the patients were immunocompromised, 11 of 14 (79%) were proven cases of blastomycosis, 7 of 14 (50%) had central nervous system (CNS) involvement, and 11 of 14 (79%) were cured. Antifungal susceptibility testing showed a consistently low minimum inhibitory concentration to ISA ≤ 0.015 mcg/mL. Conclusions This case series supports the efficacy and safety for ISA in the treatment of blastomycosis with or without CNS disseminated, especially when alternative triazoles cannot be used.

Disseminated histoplasmosis in an immunosuppressed patient successfully treated with isavuconazole

“…Patients were transitioned to isavuconazole for either adverse drug effect or drug–drug interactions with liposomal amphotericin B, for median duration of 255 days (range, 31–430 days). Eleven of the 14 cases (79%) treated with isavuconazole were considered cured after median duration of 255 days of treatment 9…”

Endemic mycoses – are we making progress in management?

“…Voriconazole has been clinically effective and is preferred over itraconazole as the 'step-down' agent in CNS disease due to the poor CNS penetration of itraconazole (in contrast to current recommendations for CNS histoplasmosis) [8,[54][55][56][57][58]. Isavuconazole is another agent with reports of clinical success in CNS disease [59].…”

“…Isavuconazole MICs are low in vitro and there are multiple clinical reports of favorable outcomes, including those with CNS disease [25,59]. Although in vitro activity is excellent, there are relatively few cases that have reported the use of posaconazole for nonsevere disease with mixed results [60,[63][64][65][66][67].…”

Diagnosis and Treatment of Fungal Infections in Lung Transplant Recipients

“…Voriconazole and posaconazole have demonstrated favorable spectrum of activities against B. dermatitidis in vitro and thus can serve as alternatives to itraconazole [ 42 , 68 ]. Isavuconazole’s use in the treatment of blastomycosis has been described in two small case series [ 72 , 154 ]. Though the echinocandins seem to display some in vitro activity, this does not correspond to clinical efficacy and thus they do not have a current role in therapy [ 43 ].…”