title: Clinical efficacy and safety of intravenous itraconazole in the management of invasive candidiasis in patients of surgery and critical care.
abstract: Although itraconazole exhibits potent activity against Candida species, there have been few studies examining the use of intravenous itraconazole in the treatment of invasive candidiasis. A nationwide multicenter clinical study was conducted to evaluate the efficacy and safety of intravenous itraconazole in the management of invasive candidiasis, including non-albicans Candida species, in non-neutropenic patients undergoing surgery and critical care. Between September 2007 and August 2009, patients with proven and presumed candidiasis were enrolled at 22 participating institutions. Patients with presumed candidiasis had a deep-body temperature of 37.8°C or higher and were positive for serum β-D: -glucan or two or more colonization sites of Candida species. The main exclusion criterion was severe renal impairment (creatinine clearance <30 ml/min). The primary efficacy analysis was based on clinical and microbiological responses 5-10 days after the end of treatment, assessed by an independent data review committee. Of the 60 patients enrolled, 49 were included in the modified intention-to-treat population; 31 patients received a definitive diagnosis and 18 patients a presumed diagnosis. Intravenous itraconazole was used as first-line therapy to treat 39 patients and as second-line therapy for 10 patients. The isolated species included Candida albicans (25 strains with definitive diagnosis and 17 with presumed diagnosis) and non-albicans species (16 and 10, respectively). Treatment was successful in 61.5% patients (65.5% in first-line and 50.0% in second-line therapy); 60% of proven invasive candidiasis (IC) patients were judged as successful compared with 63.2% of presumed candidiasis patients. Eradication rate was 63.6% for C. albicans and 71.4% for C. glabrata. Adverse effects occurred in 9 of 60 patients (15.0%), commonly impaired liver function. The clinical efficacy and safety of intravenous itraconazole were suggested in the management of proven and presumed candidiasis including C. glabrata in non-neutropenic patients. The status of intravenous itraconazole in the Japanese guideline warrants reconsideration.
authors.affiliation: Department of Infection Control and Prevention, Hyogo Medical College Hospital, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan. takesuey@hyo-med.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takesue
authors.forename: Shigeto
authors.initials: S
authors.lastname: Oda
authors.forename: Seitaro
authors.initials: S
authors.lastname: Fujishima
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.forename: Naoki
authors.initials: N
authors.lastname: Aikawa
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000382:microbiology*; D003422:Critical Care; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013503:Surgery Department, Hospital; D013514:Surgical Procedures, Operative
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole