Effect of Antifungals on Release of (1-3)-àŸ-Glucan by Aspergillus fumigatus.

M. A. S. H. MENNINK-KERSTEN, D. RUEGEBRINK, R. R. KLONT, J. DONNELLY, P. E. VERWEIJ;

Author address: 

Radboud Univ. Nijmegen Med. Ctr., Nijmegen, The Netherlands.

Abstract: 

Background: Detection of (1-3)-íŸ-Glucan (BG) is a new tool to diagnose invasive aspergillosis (IA) and other fungal infections in immunocompromised patients. We found an increase in circulating BG in a patient with proven IA (case 1) after treatment with caspofungin. We studied the effect of caspofungin on in vitro release of BG by the causative Aspergillus fumigatus strain and compared it with voriconazole. A second patient with proven cerebral aspergillosis (case 2) showed a strong increase in BG in CSF samples after treatment with amphotericin B. The causative strain was tested in vitro for BG release after exposure to caspofungin, voriconazole and amphotericin B. Methods: A. fumigatus strains were cultured in liquid medium (YNB/glucose/MOPS, pH 7.4). At different time points, samples were taken. At t=16 h, different concentrations of antifungals (caspofungin, amphotericin B, voriconazole) were added to the cultures (end concentration for case 1: 5, 10 and 20 x MIC/MEC; case 2: 0.5, 1 and 2.0 x MIC/MEC). Culture filtrates were used for BG detection (Fungitell, Associates of Cape Cod). Results: Exposure of A. fumigatus strains to caspofungin resulted in a 1365-fold (case 1) and 96-fold (case 2) increase of BG levels in the culture filtrate after exposure to 20 x MEC (case 1) and 2 x MEC (case 2) compared to the control after 72 hours of growth. Whereas the control BG levels decreased after 40 h of growth, BG levels in the cultures with caspofungin continued to increase. An increase could not be detected when A. fumigatus strains were exposed to voriconazole or amphotericin B. Conclusions: Caspofungin may result in an initial rise of circulating BG, which does not correspond with an increase in fungal load. Consequently, a BG increase during caspofungin therapy does not imply failure of treatment. The results suggest that caspofungin treatment could be used as a tool for early diagnosis and might result in an improved sensitivity of BG detection in patients at-risk.
2006

abstract No: 

M-1603

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th