An open-label study of anidulafungin in invasive candidiasis and candidaemia

R. Betts, D. Kett, K. Clark, H.T. Schlamm, D.S. Krause

Author address: 

Rochester, Miami, New York, US

Abstract: 

Objectives: Candida species (spp.) are the leading cause of invasive fungal infections in hospitalised patients (pts), and are associated with excess morbidity and mortality, despite the availability of several new agents. Anidulafungin (ANID) is a novel echinocandin with potent in vitro and in vivo fungicidal activity against Candida spp. ANID was superior to fluconazole (FLU) in a Phase 3 efficacy study of invasive candidiasis and candidaemia (IC/C) previously reported. Methods: We conducted an open-label trial of the efficacy of ANID. In contrast to the Phase 3 trial, pts on prior FLU were allowed. Adult pts with IC/C received a loading dose of ANID on Day 1 of 200 mg, then 100 mg IV daily for a total of 14-42 days. Pts could be switched to oral FLU after at least 10 days of IV ANID. Pts were assessed at the end of IV therapy (EIV), and at 2 & 6 week follow-up (FU) after the end of all therapy. A successful global response required clinical improvement and microbiological eradication. The EIV was the primary time point of interest. Safety evaluations included haematology and biochemistry labs and recording of all adverse events (AEs), regardless of attribution. Results: Thirty three (33) pts were enrolled; 22 completed through the 6-week FU visit. The mean APACHE II score was 14 (range 2-27); 20% had scores > 20. Presence of a central venous catheter was the most common (84%) reported risk factor. Most (91%) received at least one prior dose of FLU. Candidaemia was present in 90% of pts; most had multiple positive cultures at baseline. C. albicans and C. glabrata were isolated from 42% and 38% of pts, respectively. The median exposure to ANID was 14 doses. Most pts (26/33) did not switch to oral FLU. A successful global response was observed in 21/31 (67.7%) culture positive pts. Three pts (9.7%) had persistent infections. On a pathogen level, success was similar for albicans and non-albicans isolates. AEs were reported by all pts; 11 pts had AEs that were related per investigator attribution. Only 2 pts experienced AEs that led to discontinuation of study drug. At the 6 week FU 79% of pts survived. Few pts experienced infusion reactions. Clinical laboratory results did not suggest drug toxicity. Conclusions: ANID was efficacious and well tolerated. These results confirm and extend the phase 3 data previously reported.
2006

abstract No: 

P1205

Full conference title: 

16th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 16th (2006)