DOUGLAS CM, BOWMAN JC, ABRUZZO GK, FLATTERY AM, GILL CJ, KONG L, LEIGHTON C, SMITH JG, PIKOUNIS VB, BARTIZAL K, KURTZ MB, ROSEN H; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 387.
Merck & Co., Inc., Rahway, NJ
Caspofungin acetate (CAS) is a member of a new class of antifungal antibiotics that inhibit the synthesis of 1,3-beta-D glucan, an essential component of the fungal cell wall. CAS has activity against A. fumigatus and Candida albicans in vitro, and efficacy in both animal models of infection and human disease. While it is well established that CAS is fungicidal against C. albicans, the consequences of inhibiting A. fumigatus glucan synthesis are less well defined. We evaluated the anti-aspergillus activity of CAS using a novel dye-staining method in vitro and a murine pancytopenic disseminated aspergillosis survival model. At or above the MIC, the A. fumigatus hyphal tips were killed by CAS, as judged by loss of staining with a viability dye or gain of staining with a mortality dye. Chronically leukopenic mice treated with cyclophosphamide (CPY) were infected with A. fumigatus conidia, treated with CAS or amphotericin B (AmB) for 7 days, then monitored for survival for 28 days. Both CAS and AmB protected mice despite continued CPY-induced immunosuppression after therapy [effective dose 50% values (mg/kg) of 0.486 and 0.753, respectively; n = 50]. Future studies will determine if the growing cells at A. fumigatus hyphal tips are killed by CAS in vivo. *Merck & Co., Inc. Whitehouse, NJKEYWORDS: Aspergillus fumigatus; Caspofungin; Glucan synthesis
Publication Types:
Keywords:
- Amphotericin B
- Animals
- Antibiotics, Antifungal
- Antifungal Agents
- Antigens, Fungal
- Aspergillosis
- Aspergillus
- Aspergillus fumigatus
- Candida albicans
- Cyclophosphamide
- Humans
- In Vitro
- Mice
- Microbial Sensitivity Tests
- Muridae
- Peptides, Cyclic
- Proteins
- caspofungin
- immunology
Other ID:
UI: 102247814
From Meeting Abstracts