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At least 1,405 records · Page 78Linked to original sources
PubMed1983

Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans.

Amphotericin B-susceptible Candida albicans became resistant to the drug after growth in the presence of ketoconazole. Chromatographic analysis of cellular sterols showed that the organisms became depleted of ergosterol in parallel with the development of amphotericin B resistance. The implications of these findings are discussed in relation to combination chemotherapy with these two important antifungal agents.

Amphotericin B↗
PubMed1984

Fungicidal activity of tioconazole in relation to growth phase of Candida albicans and Candida parapsilosis.

It was shown that tioconazole possesses an important property not shared by ketoconazole and miconazole, its well-known relatives in the imidazole group of antifungal drugs. At a concentration of 3.8 X 10(-5) M, tioconazole, like miconazole, caused rapid 2- to 3-log reductions in CFU per milliliter when added to late-logarithmic-phase Candida albicans or Candida parapsilosis cells. Only tioconazole, however, exerted similar reductions when added to diluted stationary-phase cultures. This growth-phase-independent lethal action has important clinical implications and may explain the superior performance of tioconazole, which was observed in earlier comparative drug studies.

Antifungal Agents↗
PubMed1989

Comparative effects of the azole-based fungicide flusilazole on yeast and mammalian lanosterol 14 alpha-methyl demethylase.

Flusilazole inhibits the 14 alpha-demethylation of [24,25-3H-2]dihydrolanosterol by yeast and rat liver cell-free preparations. The 50% inhibitory concentration of demethylation shows that the yeast system is 100 times more sensitive than the rat system. Purified rat liver P-45014DM is about 10 times more sensitive to flusilazole than crude rat liver microsomes. Binding constants in microsomes indicate that yeast preparations (Kd, 21 nM) bind flusilazole with a higher affinity than rat liver (Kd, 496 nM). Purified rat liver P-45014DM (Kd, 45 nM) binds flusilazole with an affinity similar to that of the yeast enzyme. The P-450-dependent cholesterol 7 alpha-hydroxylase in rat liver microsomes is more sensitive to flusilazole than P-45014DM. The results indicate that selectivity of azole antimycotics is not due to inherent sensitivity differences between fungal and mammalian 14 alpha-demethylase; rather, in crude enzyme systems, a protective effect is afforded by other susceptible isozymes present in mammalian systems.

Animals↗
PubMed1991

Fungicidal effect of amphotericin B in urine: in vitro study to assess feasibility of bladder washout for localization of site of candiduria.

An in vitro study was performed to determine the optimum amphotericin B concentration and exposure time required to kill various strains of Candida albicans in urine. This is a preliminary study to assess the feasibility of using amphotericin B bladder washout for localization of the site of candiduria. In broth kinetic killing studies, amphotericin B at a concentration of greater than 100 micrograms/ml produced almost complete killing of 5 x 10(5) CFU of C. albicans per ml within 1.5 to 2 h. In urine studies (with various pH values, osmolalities, and electrolyte concentrations), amphotericin B at a concentration of 200 micrograms/ml with a 2-h exposure time decreased fungal counts of 21 strains of C. albicans from 5 x 10(6) to less than 200 CFU/ml. Bladder washout with greater than or equal to 200 micrograms of amphotericin B per ml and a dwell time of 2 h can therefore sufficiently sterilize the bladder of yeasts and may be a useful localization test.

Amphotericin B↗
PubMed1997

Submicellar complexes may initiate the fungicidal effects of cationic amphiphilic compounds on Candida albicans.

The killing of Candida albicans by a series of amphiphilic quaternary ammonium compounds (QACs) with different hydrocarbon chain lengths was closely related to the binding of the compounds to the cells and damage of the cell membranes. The membrane damage was measured as the level of release of the UV-absorbing material into the medium in which the cells were suspended and as the level of uptake of propidium iodide in individual cells by flow cytometry. It was shown that of the compounds tested, hexadecyltrimethylammonium bromide (cetyltrimethylammonium bromide [CTAB]) bound most efficiently. Tetradecyl betainate chloride (B14), tetradecanoylcholine bromide (C14), tetradecyltrimethylammonium bromide (TTAB), and dodecyltrimethylammonium bromide (DTAB) followed and had declining degrees of binding efficiency. The proportion of CTAB bound was almost total at concentrations up to the critical micelle concentration (CMC) of the compound, whereas that of B14 was somewhat smaller. For the two remaining tetradecyl compounds (C14 and TTAB), still smaller proportions were bound at low concentrations, but the proportions rose disproportionally at increasing concentrations to a distinct maximum at concentrations of 0.2 to 0.5 times the CMC. We propose that interfacial micelle-like aggregates are formed at the cell surface as a step in the binding process. An analogous, but less conspicuous, maximum was seen for DTAB. Thus, great differences in the binding affinity of QACs with different hydrocarbon chains at different concentrations to C. albicans were observed. These differences were related to the CMC of the compound. In contrast, the binding of TTAB to Salmonella typhimurium 395 MS was almost total at low as well as high concentrations until saturation was attained, indicating fundamental differences between binding to the yeast and binding to gram-negative bacteria. The importance of lipid-type complexes or aggregates to the antifungal effect of membrane-active substances are discussed.

Antifungal Agents↗
PubMed1997

Effect of severity of meningitis on fungicidal activity of flucytosine combined with fluconazole in a murine model of cryptococcal meningitis.

We studied the effect of the severity of meningitis on the response to therapy with fluconazole and flucytosine in a murine model of cryptococcal meningitis. Meningitis was established by intracerebral injection of Cryptococcus neoformans. The severity of meningitis was varied by delaying the onset of treatment from 3 to 7 days. Animals were sacrificed after 14 days of treatment, and the numbers of C. neoformans per gram of brain tissue were quantified. The range of effective dose combinations of fluconazole and flucytosine became progressively reduced as the severity of meningitis increased. The magnitude of treatment effect, as measured by the numbers of CFU/gram of brain tissue, was also reduced with increasing severity of meningitis. In this model, as the severity of meningitis increases, higher doses of fluconazole are required to achieve equivalent levels of activity. The combination of fluconazole and flucytosine appears to have the most-potent antifungal effects. This is most readily observed in animals with more-severe meningitis.

Animals↗
PubMed2004

Micafungin enhances neutrophil fungicidal functions against Candida pseudohyphae.

We evaluated the effect of the combination of micafungin and polymorphonuclear leukocytes (PMN) against hyphae of Candida albicans and Candida dubliniensis. Micafungin enhanced the PMN oxidative burst dose dependently. The combination was synergistic (C. albicans) or additive (C. dubliniensis); when PMN were pretreated with granulocyte-macrophage colony-stimulating factor, the combination was more effective.

Candida↗
PubMed1983

Soil Fungicides for Controlling Chytridiaceous Mycoparasites of Gigaspora margarita and Glomus fasciculatum.

The percentage of azygospores of Gigaspora margarita with zoosporangia of chytridiaceous fungi (CF) was reduced significantly after agitating them in fenaminosulf before incubation in soil. Fenaminosulf did not affect zoosporangia development on chlamydospores of Glomus fasciculatum. Metalaxyl and ethazol were not effective against CF on spores of either mycorrhizal fungus. Azygospores of G. margarita were treated with fenaminosulf and used as the inoculum for pot cultures. After 19 weeks, the percentage of azygospores containing CF was reduced significantly by this treatment, whereas root colonization and sporulation by the mycorrhizal fungus were unaffected. Pot cultures of G. margarita, either drenched with fenaminosulf or not, did not differ in the percentage of azygospores containing CF. However, root colonization and sporulation by the mycorrhizal fungus was temporarily delayed when pots were drenched with fenaminosulf.

Journal Article↗
PubMed1992

Natamycin as a fungicide in agar media.

Fungal inhibition in four commonly used agar media was improved by substituting natamycin (pimaricin) for cycloheximide. The recovery of bacteria was not affected by natamycin, whereas fungal contamination from a variety of samples was significantly suppressed. Furthermore, natamycin lacks the occupational health hazards of cycloheximide. Medium-dependent natamycin degradation occurred during the preparation and refrigerated storage of agar plates, but the addition of natamycin at 21.6 mug/ml resulted in effective residual activity.

Journal Article↗
PubMed1975

Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes.

Granulocytes from the peripheral blood of normal subjects and a patient with hereditary myeloperoxidase deficiency were homogenized in 0.34 M sucrose. A granule-rich fraction, prepared by sedimentation at 27,000 x g for 20 min, contained components that killed C. parapsilosis in vitro. These were extractable with 0.01 M citric acid and were shown by micropreparative polyacrylamide electrophoresis to be multiple. The candidacidal activity of these neutrophil components was heat stable and they were somewhat more active at pH 5.0 than at pH 7.0. When rabbit or guinea pig heterophils were obtained from sterile peritoneal exudates and similarly fractionated, they also were found to contain components that killed C. parapsilosis in vitro. These were primarily associated with a group of lysosomal cationic proteins lacking direct counterpart in human neutrophils. Among the candidacidal components of the human neutrophil was a protein, more cationic than lysozyme, that exhibited naphthol-ASD acetate esterase activity.

Animals↗