Cilofungin (LY121019), an antifungal agent with specific activity against Candida albicans and Candida tropicalis

Hall, Gerri S.; Myles, C; Pratt, Kathleen; Washington, John A.

doi:10.1128/aac.32.9.1331

Cited by 64 publications

(29 citation statements)

References 18 publications

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“…A similar phenomenon has also been observed with fungi (2,11,15). In the course of this study, four strains produced such an effect with itraconazole alone and in combination with concentrations of pentamidine below 1 jig/ml.…”

Section: Discussionsupporting

confidence: 51%

Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans

St-Germain

1990

Antimicrob Agents Chemother

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The in vitro interaction of pentamidine with ketoconazole and with itraconazole was studied with 10 strains of Candida albicans isolated from acquired immunodeficiency syndrome patients and one azole-resistant strain. Although growth curves indicated that concentrations of 1 ,g or more of pentamidine per ml significantly inhibited the growth of C. albicans, MICs and minimum fungicidal concentrations (MFCs) were .10 ,g/ml. Combinations of ketoconazole and pentamidine did not appear to have any significant effect on MICs or MFCs with most strains. However, the azole-resistant strain exhibited a 2-log decrease in MIC when exposed to ketoconazole combined with 1.0 ,ug or more of pentamidine per ml. Similar results were obtained with itraconazole. An Eagle, or paradoxical, effect was observed with four strains exposed to itraconazole alone and in combination with 0.01 and 0.1 ,ug of pentamidine per ml. This effect was not seen when concentrations of pentamidine reached 1.0 ,ug/ml. Although no fungicidal effect was observed with any of these drugs alone, itraconazole combined with 10 ,Ig of pentamidine per ml was fungicidal for eight strains. No signs of antagonism between pentamidine and these two antifungal agents were observed.

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Section: Discussionsupporting

confidence: 51%

Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans

St-Germain

1990

Antimicrob Agents Chemother

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“…The pioneer echinocandin was cilofungin, which has a narrow in vitro spectrum that is practically confined to Candida spp. (11,12). In a model of systemic coccidioidomycosis, cilofungin did not prolong survival or reduce tissue fungal counts (6).…”

Section: Discussionmentioning

confidence: 99%

Correlation between Antifungal Susceptibilities of Coccidioides immitis In Vitro and Antifungal Treatment with Caspofungin in a Mouse Model

González

Tijerina

Najvar

et al. 2001

Antimicrob Agents Chemother

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Caspofungin (Merck Pharmaceuticals) was tested in vitro against 25 clinical isolates of Coccidoides immitis.In vitro susceptibility testing was performed in accordance with the National Committee for Clinical Laboratory Standards document M38-P guidelines. Two C. immitis isolates for which the caspofungin MICs were different were selected for determination of the minimum effective concentration (MEC), and these same strains were used for animal studies. Survival and tissue burdens of the spleens, livers, and lungs were used as antifungal response markers. Mice infected with strain 98-449 (48-h MIC, 8 g/ml; 48-h MEC, 0.125 g/ml) showed 100% survival to day 50 when treated with caspofungin at >1 mg/kg. Mice infected with strain 98-571 (48-h MIC, 64 g/ml; 48-h MEC, 0.125 g/ml) displayed >80% survival when the treatment was caspofungin at >5 mg/kg. Treatment with caspofungin at 0.5, 1, 5, or 10 mg/kg was effective in reducing the tissue fungal burdens of mice infected with either isolate. When tissue fungal burden study results were compared between strains, caspofungin showed no statistically significant difference in efficacy in the organs of the mice treated with both strains. A better in vitro-in vivo correlation was noted when we used the MEC instead of the MIC as the endpoint for antifungal susceptibility testing. Caspofungin may have a role in the treatment of coccidioidomycosis.

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“…As was determined for the native compounds, cilofungin was found to have fungicidal activity, but only for actively growing cells. A number of subsequent reports have confirmed the high level of in vitro activity that is essentially limited to members of the genus Candida, with highest activity against C. albicans and C. tropicalis (102,116,158,159,225,228,231). Several peculiarities or restrictive conditions with in vitro tests with this compound have been documented, including demonstration of the Eagle effect (102,228) and effects of pH (158) and inoculum size (102).…”

Section: Inhibitors Of Glucan Synthesismentioning

confidence: 90%

Compounds active against cell walls of medically important fungi

Hector

1993

Clin Microbiol Rev

217

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A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development.

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Cilofungin (LY121019), an antifungal agent with specific activity against Candida albicans and Candida tropicalis

Cited by 64 publications

References 18 publications

Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans

Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans

Correlation between Antifungal Susceptibilities of Coccidioides immitis In Vitro and Antifungal Treatment with Caspofungin in a Mouse Model

Compounds active against cell walls of medically important fungi

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