Posaconazole as salvage therapy for zygomycosis

Abstract

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

FIG. 1.

Kaplan-Meier survival curves for underlying disease, zygomycosis infection, and actuarial disease (all 24 subjects). Crosses indicate deaths or end of treatment with posaconazole. The solid line represents percent survival from underlying disease; it does not consider any specific antifungal therapy or surgery. Those deaths were due to complications from patients underlying condition and not due to zygomycosis. The dotted line represents percent survival from zygomycosis. Those deaths were due only to zygomycosis. The hatched line represents survival considering all causes. The inset expands the view of percent survival during the first 40 days of posaconazole treatment. All deaths from zygomycosis occurred early in treatment, suggesting posaconazole treatment for more than 30 days is associated with long-term survival. Deaths not due to zygomycosis but from underlying disease were more likely after 40 days of posaconazole treatment.