In Animals
Guidelines for the management of veterinary blastomycosis are currently available for cats as part of guidelines for the prevention and management of rare systemic mycoses published in 2013 by the European Advisory Board on Cat Diseases (Lloret et al.
2013). These suggest that itraconazole (10 mg/kg once daily) should be the preferred therapy for most cases, usually given for >3 months and that amphotericin B (0.25 mg/kg every 48 h to a total dose of 4-16 mg/kg) or fluconazole (2.5-10 mg/ kg twice daily) are preferred for severe cases or those with CNS involvement (Lloret et al. 2013).No guidelines currently exist for the diagnosis or management of canine blastomycosis. Randomized controlled trials do not exist to guide management decisions, but several prospective and retrospective studies of canine blastomycosis are instructive.
Legendre et al. prospectively treated 112 dogs with blastomycosis with itraconazole at doses of 5 or 10 mg/kg daily for 60 days and compared outcomes to historical controls treated with amphotericin B (at a cumulative dose of 8-9 mg/ kg) in a study setting (Legendre et al. 1996). No differences were observed in outcomes between dogs treated with either of the itraconazole doses and amphotericin B: cure was achieved in 54-57% of all dogs, with disease recurring in 20-21% and death in 23-26% (Legendre et al. 1996). These observations are for the most part congruent with other reports (Arceneaux et al. 1998).
Fluconazole has been suggested by some authors as a reasonable (and cheaper) alternative to itraconazole in the treatment of canine blastomycosis (Mazepa et al. 2011). In vitro susceptibility testing on a small number of human B. dermatitidis isolates suggests fluconazole has less activity than itraconazole (Li et al. 2000; Gonzalez et al. 2005). While no trial has compared these head-to-head, small single-arm trials in humans are informative.
In a prospective, open-label trial of 48 persons with non-life-threatening, non-CNS blastomycosis, itraconazole (at a dose of 200-400 mg daily, for a mean of 6 months) resulted in 90% success (response with no relapse by 1 year follow-up) (Dismukes et al. 1992). In contrast, a trial of fluconazole at a dose of 400-800 mg daily (for a mean of 8.9 months) in 39 patients with non-life-threatening, non-CNS blastomycosis resulted in successful outcome in 87% (Pappas et al. 1997). Prospective trials are lacking in dogs, but Mazepa et al. (2011) retrospectively compared 36 and 31 dogs treated with fluconazole and itraconazole, respectively. The study was not powered to detect a difference in outcomes, but dogs treated with fluconazole required longer courses of therapy than those treated with itraconazole (median 183 vs 138 days, respectively). Nonetheless, costs for fluconazole were much less than for itraconazole, with median costs of $1223 and $3717, respectively (Mazepa et al. 2011). Taken together, this data suggests that fluconazole at higher doses and for longer courses may be reasonable alternatives to itraconazole for blastomycosis in animals.For CNS and ocular disease, fluconazole achieves better penetration than itraconazole into these structures (Perfect et al. 1986; Savani et al. 1987), although both drugs were effective in animal models of non-blastomycotic fungal meningitis (Perfect et al. 1986) and endophthalmitis (Savani et al. 1987).
Adjunctive systemic corticosteroids have been suggested for ocular blastomycosis in dogs. In a retrospective study of 12 dogs with ocular involvement in 19 eyes, systemic corticosteroids were administered in addition to triazoles (Finn et al. 2007). The success rate in this series was 74% across all eyes involved, including 67% of eyes with endophthalmitis, the most common complication that generally carries a poor prognosis (Finn et al. 2007). For comparison, another retrospective study of itraconazole monotherapy for ocular blastomycosis reported favorable outcomes in just 13% of eyes with endophthalmitis (Brooks et al. 1992). In another study, amphotericin B plus ketoconazole resulted in favorable outcomes for 20% of eyes with endophthalmitis, although this improved to 43% if only non-severely affected eyes were considered (Bloom et al. 1996).
8.5.3