title: Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses.
abstract: 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.
authors.affiliation: Department of Medicine/Division of Infectious Diseases, University of California-Davis Medical Center, Sacramento.
authors.forename: George R
authors.initials: GR
authors.lastname: Thompson
authors.affiliation: CIPTIR, Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Adrian
authors.initials: A
authors.lastname: Rendon
authors.affiliation: Universidade Federal de Minas Gerais, Santa Casa de Belo Horizonte.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ribeiro Dos Santos
authors.affiliation: Department of Public Health Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Flavio
authors.initials: F
authors.lastname: Queiroz-Telles
authors.affiliation: University of Texas Medical School at Houston and Memorial Hermann-Texas Medical Center.
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.affiliation: Astellas Pharma Global Development, Inc, Northbrook, Illinois.
authors.forename: Nkechi
authors.initials: N
authors.lastname: Azie
authors.affiliation: Astellas Pharma Global Development, Inc, Northbrook, Illinois.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Maher
authors.affiliation: Astellas Pharma Global Development, Inc, Northbrook, Illinois.
authors.forename: Misun
authors.initials: M
authors.lastname: Lee
authors.affiliation: Astellas Pharma Global Development, Inc, Northbrook, Illinois.
authors.forename: Laura
authors.initials: L
authors.lastname: Kovanda
authors.affiliation: Basilea Pharmaceutica International Ltd, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Engelhardt
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Medical College of Georgia/Georgia Regents University, Augusta.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Vazquez
authors.affiliation: Department of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.affiliation: Department of Medicine/Division of Infectious Diseases, Duke University, Durham, North Carolina.
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000494:pharmacology*; D001759:Blastomycosis / Q000188:drug therapy / Q000382:microbiology; D003047:Coccidioidomycosis / Q000188:drug therapy / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D006660:Histoplasmosis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D009570:Nitriles / Q000009:adverse effects / Q000494:pharmacology*; D010229:Paracoccidioidomycosis / Q000188:drug therapy / Q000382:microbiology; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology*; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D009570:Nitriles; D011725:Pyridines; D014230:Triazoles; C508735:isavuconazole
keywords: blastomycosis; coccidioidomycosis; cryptococcosis; histoplasmosis; paracoccidioidomycosis