Posaconazole therapy for chronic refractory coccidioidomycosis

Background: Coccidioides infections often result in chronic relapsing disease that presents a challenge to the currently available therapy. Posaconazole, an oral extended-spectrum triazole agent, has been shown in vitro and in vivo to have potent activity against this fungus. Methods: An open-label multinational study of posaconazole, 800 mg/d, administered in divided doses for the treatment of invasive fungal infection that has been refractory to previous therapy was conducted. The data were reviewed by an independent data review committee (DRC). Fifteen patients met the criteria for proven coccidioidal infection and disease refractory to previous therapy. Success was a complete or partial response; nonsuccess was stable disease, lack of response to therapy, or undetermined response. Results: The sites of coccidioidal infection were pulmonary (seven patients) and disseminated (eight patients). Patients were refractory to previous therapy (including amphotericin B with or without an azole) for a median duration of 306 days. At the end of treatment (posaconazole treatment duration, 34 to 365 days), therapy for 11 of 15 patients (73%) was considered to be successful by the DRC. Four responses were complete and seven were partial; these included five patients with pulmonary sites and six patients with disseminated sites. In responders, improvement was seen within months of the initiation of therapy. Five patients received therapy for > 12 months. The side effects were minimal. Conclusions: Therapy for coccidioidomycosis remains a clinical challenge, especially when patients have not responded to therapy with drugs that were recommended in treatment guidelines. The success rate (73%) achieved in this case series suggests that oral posaconazole should be considered as an important agent for the treatment of refractory coccidioidomycosis.