Activity of posaconazole in invasive fungal infections associated with a variety of moulds and yeasts

S. Haider*, M. Laverdiere, C. Rotstein, K. Doucette, M. Power, J. Lipton, P. Phillips, A. Galarneau, J.-F. Pouliot

Author address: 

(Hamilton, Montreal, Toronto, Alberta, Vancouver, CA)

Abstract: 

Objective: Invasive fungal infections (IFIs) cause serious complications in immunosuppressed patients. Although Candida and Aspergillus species (sp) are the most common pathogens, other rare fungi can occasionally be involved. Extensive use of azoles as first line therapy may result in the emergence of less common fungal infections. Posaconazole is a second generation antifungal drug with wide yeast and mould coverage and could play a role in the treatment of these rare infections. Methods: This is a multicenter single arm phase II study of Posaconazole (400 mg BID) in patients with IFIs who have failed or been intolerant to only one prior line of therapy. The primary objectives are safety and efficacy. Safety was evaluated in all patients; efficacy on those who survived more than 7 days.Results: Forty patients were included in the study of which 29 (73%) had proven or probable IFIs. Conditions leading to IFI were AML (31%), stem cell transplant (26%), lung transplant (11%), renal transplant (9%), pulmonary disease (9%) and others (14%). A specific organism could be indentified in 30 patients, with Aspergillus sp representing the majority of cases (55%). A. fumigatus was the most common sp but A. niger, A. flavus and A. cervinus were also found. Candida sp accounted for 18% of fungi: C. albicans, C. glabrata and C. kruseı¨ were detected. Less common fungi such as mucormycetes (Rhizomucor and Rizopus), Cocciodioides, Exophiala, Fusarium and Histoplasma were also identified. Prior therapy included voriconazole (47%), amphotericin B (28%), fluconazole (16%) and others (9%). Patients were either refractory (70%) or intolerant (30%) to these prior therapies. Efficacy could be evaluated in 32 patients at the time of analysis. Response rate in both proven and probable infected patients based on the EORTC criteria was 53% (9% CR and 43% PR); two patients with early death were classified as non responders. The response rates were similar in all patients including those infected with rare fungi and those with possible infections. Safety was assessed in all 40 patients common toxicities reported were: nausea and vomiting (26%), diarrhea (26%), rash (15%), edema (12%) and elevated liver enzymes (9%). No drug related grade 4 toxicities were reported. Conclusion: Several less common fungi were isolated supporting the emergence of rare sp. Posaconazole was equally effective in all patients and may represent a valuable alternative even after prior exposure to other azoles.
2012

abstract No: 

p846

Full conference title: 

22nd European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 22nd (2012)