Paclitaxel Interference with the Antifungal Activities of Amphotericin B.

S.K. MISHRA, R. RAMANI, L.K. YANKOV, A. SHARMA, T. TREVASKISS, R. MISRA, and R.C. PANDEY

Abstract: 

Paclitaxel is a novel anti-cancer drug with a unique mode of action. During the past five years, it has emerged as a drug of choice for the treatment of ovarian and breast cancers, and is recently approved for Kaposi sarcoma. It is likely to become a useful anti-neoplastic agent for a wide range of other cancerous conditions. However, secondary opportunistic systemic fungal infections frequently complicate prognosis in cancer cases. At that stage, amphotericin B is often the drug of choice. Present study was prompted by a lack of information concerning synergism between these two drugs. Using a method developed by the National Committee for Clinical Laboratory Standards, 63 strains of fungi (25 azole resistant), representing Candida albicans, C. glabrata, Cryptococcus neoformans, Saccharomyces cerevisiae, Aspergillus fumigatus, A. niger, A. flavus and Cladosporium species were tested against amphotericin B and paclitaxel, separately and in combinations. In contrast to most of the microbial produced anti-cancer drugs, paclitaxel showed no anti-fungal property at tested concentrations (0.3 to 3.0 mg/ml). The MIC of amphotericin B alone against these strains ranged from 0.06 micro g/ml to 1.0 micro g/ml. Amphotericin B failed to inhibit fungal growth at any of the tested concentrations when combined with 0.1, 0.3 or 3.0 mg/ml of paclitaxel. The fungal growth was however, inhibited in assays containing 1.0 micro g/ml of amphotericin B and an excessively high concentration (6.0 mg/ml) of paclitaxel. These observations stress a need to evaluate other antifungal drugs for synergism with paclitaxel.
1998

abstract No: 

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Full conference title: 

38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th