Clinical efficacy and safety of intravenous itraconazole in the management of invasive candidiasis in patients of surgery and critical care.

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.