391. Evaluation of Second-Generation Triazoles in the Treatment of Refractory Coccidioidomycosis

Background Coccidioidomycosis is a systemic fungal infection endemic to the southwestern United States. Although most cases are self-limiting and restricted to the lungs, the disease can disseminate to the bone, soft tissue, and central nervous system (CNS). First-line therapy generally consists of fluconazole or itraconazole. In cases refractory to first-line therapy, the management is less well defined. Newer triazole antifungals, such as posaconazole (POSA) and voriconazole (VORI), have demonstrated efficacy in refractory cases, but data are limited. Isavuconazole (ISAV) has in vitro activity against Coccidioides spp., but in vivo data are limited to nine cases of primary pulmonary disease. To our knowledge, there are no published studies regarding its role in refractory cases. Any treatment outcomes data with these agents would contribute to the limited scientific body. Methods Retrospective chart review of patients with refractory coccidioidomycosis whose therapy was changed to ISAV, POSA, or VORI between January 1, 2010 and April 18, 2018. Outcome was defined as improved, stable, or unresponsive utilizing the Mycosis Study Group (MSG) score (a composite score for symptoms, serology, radiographic findings) and the documented impressions of treating physicians. For CNS patients, a separate point system was used to compute the score. Results Of the patients meeting study criteria, 15 patients received ISAV, 32 patients received POSA (suspension n = 12, tablets n = 19), and 21 patients received VORI. In the ISAV group, 73.3% of patients were improved, and 26.7% were stable. In the POSA suspension group, 83.3% were improved and 16.7% were stable compared with 78.9% improved and 21.1% stable in the POSA tablet group. In the VORI group, 61.9% were improved, 19% were stable, and 19% were unresponsive. MSG scores across all treatment groups were reduced (P < 0.003) with a median change of −2, −4, −2.5, −2 for ISAV, POSA suspension, POSA tablets, and VORI, respectively. Conclusion Isavuconazole, posaconazole, and voriconazole are reasonable options for treatment of refractory coccidioidomycosis. Prospective comparative trials are required to provide further insights into their efficacy and utility. Disclosures All authors: No reported disclosures.