Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses

George R. Thompson, Adrian Rendon, Rodrigo Ribeiro Dos Santos, Flavio Queiroz-Telles, Luis Ostrosky-Zeichner, Nkechi Azie, Rochelle Maher, Misun Lee, Laura Kovanda, Marc Engelhardt, Jose A. Vazquez, Oliver A. Cornely, John R. Perfect

Research output: Contribution to journalReview articlepeer-review

86 Scopus citations

Abstract

Background. 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. Methods. 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. Results. 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. Conclusions. 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. Clinical Trials Registration. NCT00634049.

Original languageEnglish (US)
Pages (from-to)356-362
Number of pages7
JournalClinical Infectious Diseases
Volume63
Issue number3
DOIs
StatePublished - Aug 1 2016

Keywords

  • blastomycosis
  • coccidioidomycosis
  • cryptococcosis
  • histoplasmosis
  • paracoccidioidomycosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses'. Together they form a unique fingerprint.

Cite this