Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monotherapy, in the form of amphotericin B or one of its liposomal derivatives, is the usual treatment for invasive fungal infections, due to lack of a safe, effective combination of antifungal drugs. Combination therapy is not necessarily beneficial-there may be mutual antagonism or indifference, increased toxicity or interference with concomitant medication. But the benefits of a well-tolerated, synergistic combination would be great-the enhanced efficacy would improve clinical outcome, reduce the need for prolonged courses of treatment and prevent the emergence of antifungal drug resistance. Antifungal antibodies would be a natural partner in a combinatorial approach to antifungal therapy. Analysis of the antibody response which occurs in patients with invasive candidiasis, being treated with amphotericin B, showed a close correlation between recovery and antibody to the immunodominant heat shock protein 90 (hsp90). The molecular chaperone hsp90 is essential for yeast viability. Mycograb is a human recombinant antibody to hsp90 which shows intrinsic antifungal activity and synergy with amphotericin B both in vitro and in vivo. It is now the subject of a multinational, double-blind, placebo-controlled trial, in patients with culture-confirmed invasive candidiasis on liposomal amphotericin B.
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PMID:Recombinant antibodies: a natural partner in combinatorial antifungal therapy. 1504 Sep 39

Anidulafungin, an echinocandin, is in late stage development for the treatment of fungal infections. We investigated the activity of anidulafungin in combination with other antifungal agents (fluconazole, itraconazole, ketoconazole, amphotericin B and 5-fluorocytosine) against four isolates each of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis, and two isolates of Candida krusei using a macrobroth chequerboard method with interactions evaluated by fractional inhibitory concentration indices (FICIs). Additive activity (FICI > 0.5 to 1) or indifference (FICI > 1 to < 4) was observed in 85 of 90 interactions of anidulafungin with another antifungal agent. Synergy with itraconazole (FICI<or=0.5) was observed for one strain of C. glabrata, and antagonism with ketoconazole (FICI>or=4), a drug rarely used systemically, was noted for four strains of C. tropicalis. The combination of anidulafungin and amphotericin B demonstrated additive activity for each of the 18 isolates of Candida tested. These results suggest additional studies are warranted, for example in animal models, to evaluate further the potential of combination antifungal therapy with anidulafungin for Candida infections.
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PMID:In vitro interactions of anidulafungin with azole antifungals, amphotericin B and 5-fluorocytosine against Candida species. 1641 47