Activity In Vitro of 27 Combinations of Licensed Antifungal Agents against Scedosporium apiospermum (Sa) and Scedosporium prolificans (Sp).

M. CUENCA-ESTRELLA1, A. GOMEZ-LOPEZ 2, L. ALCAZAR-FUOLI 2, M. J. BUITRAGO 2, E. MELLADO 2, J. L. RODRIGUEZ-TUDELA 2;

Author address: 

1Inst. de Salud Carlos III. Centro Nacional de Microbiologí­a, Madrid, Spain, 2Instituto de Salud Carlos III. Centro Nacional de Microbiologí­a, Madrid, Spain.

Abstract: 

Background: Sa and Sp have been associated with invasive infections difficult to treat. They exhibit resistance in vitro against antifungal agents. We have analyzed the combined activity of antifungal agents against 12 strains of Sa and 12 of Sp. Methods: A checkerboard technique was performed. A total of 27 double combinations were tested: amphotericin B (AMB) plus flucytosine (FC), AMB-itraconazole (ITC), AMB-voriconazole (VRC), AMB-posaconazole (POS), AMB-ravuconazole (RVC), terbinafine (TBF) plus VRC, TBF-ITC, TBF-POS, and TBF-RVC; in addition, AMB, azole agents and TBF were tested in double combinations with caspofungin (CPF), micafungin (MCF), and anidulafungin (ADF). The combined effects were analyzed by the summation of fractional concentration index (FIC), and defined as synergistic if FIC 8804; 0.5, indifferent if > 0.5 but 8804; 4, and antagonistic if > 4. Results: For Sa, an average indifferent effect was detected for combinations including AMB, FC, TBF. However, synergy was detected for combinations of azole agents and echinocandins, particularly ITC-CPF with average FIC of 0.29, ITC-MCF:0.24, ITC-ADF:0.49, VRC-CPF: 0.41, VRC-MCF:0.36, POS-CPF: 0.39, POS-MCF:0.39, RVC-CPF:0.34, RVC-MCF:0.28, and RVC-ADF:0.44. Combinations of azoles plus TBF had synergy against around 50% of Sa isolates. For Sp, all combinations were indifferent but synergy was detected for 20-25% of isolates for AMB-VRC, VRC-TBF, RVC-TBF, and RVC-CPF. Conclusions: (i) Combinations including an azole and an echinocandin exhibited synergy against most of Sa isolates analyzed. (ii) Combinations with AMB, FC or TBF had an indifferent effect for Sa. (iii) All combinations were indifferent against Sp but synergy was observed for some isolates, particularly for combinations with an azole plus TBF.
2006

abstract No: 

M-296

Full conference title: 

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