isavuconazole and Coccidioidomycosis

Coccidioidomycosis manifests as a variety of clinical manifestations and ranges in severity from asymptomatic exposure with resultant immunity to reinfection, to fulminant, and life-threatening disseminated disease. Primary coccidioidal pneumonia represents the most common clinical form of infection, and the incidence continues to increase. Within the endemic region, primary pulmonary coccidioidomycosis represents up to 29% of all community-acquired pneumonia emphasizing the frequency with which clinicians encounter this endemic mycosis. Chronic infection develops in 3 to 5% of patients, and almost all morbidity and mortality observed in coccidioidomycosis occur in these forms (e.g., chronic pulmonary disease, extrapulmonary manifestations). This review summarizes the ecology, epidemiology, manifestations of disease, and treatment options currently available for coccidioidomycosis.

Topics: Antifungal Agents; Coccidioides; Coccidioidomycosis; Humans; Nitriles; Pneumonia; Pyridines; Risk Factors; Triazoles; Voriconazole

Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV.. The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed.. Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events.. ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents.. NCT00634049.

Topics: Adult; Aged; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Male; Middle Aged; Mycoses; Nitriles; Paracoccidioidomycosis; Pyridines; Triazoles; Young Adult

Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles that necessitate evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis.

Topics: Antifungal Agents; Coccidioides; Coccidioidomycosis; Humans; Triazoles

Coccidioidal meningitis remains difficult to treat. The newer triazole, isavuconazole, has demonstrated efficacy in invasive fungal disease with less side effects than other azoles. We describe a case of refractory pediatric coccidioidal meningitis with disease stabilization and improvement on isavuconazole after failing treatment with other antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Child; Coccidioides; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Humans; Meningitis, Fungal; Nitriles; Pyridines; Salvage Therapy; Triazoles; Voriconazole

Patients with coccidioidal meningitis require lifelong antifungal therapy. Cumulative toxicity and lack of antifungal efficacy require salvage therapy in the treatment of some patients. In a retrospective review of nine patients with coccidioidal meningitis treated with isavuconazole, successful therapy was seen in three patients and stable disease was confirmed in six patients. Isavuconazole may be a useful addition to the therapeutic choices currently available for coccidioidal meningitis.

Topics: Adult; Antifungal Agents; Coccidioidomycosis; Female; Humans; Male; Meningitis, Fungal; Middle Aged; Nitriles; Pyridines; Retrospective Studies; Treatment Outcome; Triazoles