Biomedical subjects

S Hawser

Publications and source records attributed to S Hawser.

10 recordsLinked to original sources

PubMed2004

In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae.

The in vitro activities of iclaprim, a novel dihydrofolate reductase inhibitor, azithromycin, and levofloxacin were tested against 10 strains of Chlamydia trachomatis and 10 isolates of Chlamydia pneumoniae. For C. trachomatis and C. pneumoniae, the iclaprim MIC and minimal bactericidal concentration at which 90% of isolates were inhibited (MIC(90) and MBC(90)) were 0.5 micro g/ml, compared to an azithromycin MIC(90) and MBC(90) of 0.125 micro g/ml and levofloxacin MIC(90)s and MBC(90)s of 1 micro g/ml for C. trachomatis and 0.5 micro g/ml for C. pneumoniae.

Anti-Bacterial Agents↗

PubMed1999

Comparisons of the effects of fungicidal and fungistatic antifungal agents on the morphogenetic transformation of Candida albicans.

Eleven different antifungal agents were compared, and their ability to inhibit the morphogenetic transformation of Candida albicans was examined together with their ability to inhibit growth, as measured by MIC methodology. The fungicidal potential of each agent was also determined. Of the antifungal agents tested, only amphotericin B, mulundocandin and aculeacin inhibited the transformation at sub-MIC values; all three agents showed fungicidal activity at concentrations close to the MIC. All other agents were fungicidal only at concentrations much higher than the MIC and inhibited the morphogenetic transformation only at concentrations above the MIC. These data suggest that fungicidal antifungal agents are more likely to act by inhibiting the morphogenetic transformation of C. albicans while fungistatic agents are unable to do so and are more likely to block growth by budding.

Antifungal Agents↗

PubMed1999

Mulundocandin, an echinocandin-like lipopeptide antifungal agent: biological activities in vitro.

Mulundocandin (MCN) is an antifungal lipopeptide which belongs to the echinocandin class of antimycotic agents. MCN exhibited good in vitro activity against Candida albicans and C. glabrata isolates with MIC ranges of 0.5-4.0 microg/ml and 2.0-4.0 microg/ml, respectively. MCN also exhibited some activity against C. tropicalis isolates (MIC range 1.0-8.0 microg/ml). However, MCN was poorly active against other non-albicans isolates and was inactive against Cryptococcus neoformans, Aspergillus species and Trichophyton. MCN appeared to exert its antifungal activity through preferential inhibition of germ tube formation (MIC-HY 0.015-0.03 microg/ml) and was typically less active on the yeast form (MIC 0.5-4.0 microg/ml). In kill-curve experiments 99.9% reductions in cell viability were observed following 8 hours exposure to MCN at 4 x MIC and 8 x MIC and after 5 hours exposure to 16 x MIC.

Antifungal Agents↗

PubMed1999

Anidulafungin (Eli Lilly & Co).

The pentyloxyterphenyl side chain derivative of echinocandin B, anidulafungin, is a 1,3-alpha-glucan synthesis inhibitor undergoing phase II clinical trials by Versicor and Eli Lilly, in various formulations, for the potential treatment of fungal and protozoal infections. Eli Lilly has retained options to the oral formulation of the compound, but development, clinical registration and marketing rights were licensed to Versicor in June 1999. The primary target of this compound is Candida, but Eli Lilly also intends to develop the drug for Aspergillus infections. No activity has been shown against Cryptococcus. The oral activity of anidulafungin is compromised by a low bioavailability, a decreased absorption when taken with food, and gastrointestinal side effects at higher doses. The development of a phosphorylated prodrug, LY-307853, which is converted in the body to anidulafungin by tissue and serum phosphatases, was discontinued in favor of an oral formulation, which uses anidulafungin directly. In February 1999, Deutsche Bank predicted sales of $100 million in 2001, rising to $300 million in 2003.

Journal Article↗

PubMed1998

3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces sp. HAG 003874.

New antifungal antibiotics, designated as 3874 H1 and H3, were discovered in the fermentation broth of the strain Streptomyces sp. HAG 003874. The compounds were obtained as yellow powders after sequential purification by chromatography on MCI Gel CHP20P, Fractogel HW-40 and ODS reversed phase chromatography. On the basis of the results of spectroscopic analysis, it was found that 3874 H1, C58H86N2O18, MW 1098, belongs to the p-aminoacetophenone containing family of heptaene antibiotics, while 3874 H3, C57H87NO18, MW 1073, is a non-aromatic heptaene. In addition to these, a minor component, 3874 H2, C59H88N2O18, MW 1112, a N-methyl derivative of 3874 H1 has been detected. The structures were elucidated through mass spectral analyses and 1-D and 2-D homonuclear and heteronuclear NMR data. The outstanding physico-chemical feature of 3874 H3 is its improved solubility. The new heptaenes are potent antifungal compounds with broad activity spectra, encompassing dermatophytes, yeasts and filamentous fungi.

Anti-Bacterial Agents↗

PubMed1996

Spectrophotometric determination of the morphogenetic transformation by synchronous Candida albicans: effects of antifungal agents.

A spectrophotometric method for studying the morphogenetic transformation by Candida albicans is described. Synchronous yeast-phase C. albicans cells incubated at 35 degrees C formed germ-tubes and resulted in an absorbance increase at 340 nm but not at 595 nm. Furthermore, measurements of germ tube length increases correlated strongly (r2 > 0.95) with increases in absorbance at 340 nm during the morphogenetic transformation. Amphotericin B significantly affected the morphogenetic transformation, at the MIC and 1/10 MIC, whereby no increase in absorbance was observed at 340 nm. In contrast, identical measurements demonstrated that ketoconazole, at the MIC and 1/10 MIC, did not exhibit the same effects on the morphogenetic transformation by C. albicans cells.

Antifungal Agents↗

PubMed1996

The effects of antifungal agents on the morphogenetic transformation by Candida albicans in vitro.

The effects of antifungal agents, with different mechanisms of action, on the morphogenetic transformation by synchronised yeast-phase Candida albicans cells in vitro and their respective anti-Candida activities are described. MIC data demonstrated that the azoles, amphotericin B and echinocandin were the most active agents against four C. albicans strains. Morphogenetic transformation experiments demonstrated that amphotericin B was significantly better at preventing the transformation, under a variety of test conditions, than the azoles and flucytosine: amphotericin B abolished the transformation at low concentrations while the azoles only prevented the morphogenetic transformation at much higher concentrations (> 100 x MIC).

Antifungal Agents↗

PubMed1989

Changes in internal and external pH accompanying growth of Candida albicans: studies of non-dimorphic variants.

Non-dimorphic variants of Candida albicans, which were unable to form germ tubes or mature hyphae in media containing amino acids, glucose and salts or N-acetylglucosamine or serum, were prepared from two hyphal positive laboratory strains using a physical separation method. The hyphal-minus phenotype was stable and may be due to mutations or phenotypic variation. The variant strains maintained their internal pH within narrower bounds as compared to their parental wild-types. When exposed to conditions that normally supported the induction of germ tubes the cytoplasmic pH of the wild type strains increased from 6.8 to over pH 8.0 within 5 min while in the variants the rise in internal pH was only about 0.3 pH units. The wild type strains acidified the growth medium more rapidly than the variants. The results suggest that the control of internal pH is directly or indirectly associated with the regulation of dimorphism. The variants had unaltered cell volumes and specific growth rates. The hyphal-minus phenotype was however fully reversible since revertants occurred spontaneously on serum containing agar.

Candida albicans↗

PubMedDate not supplied

Comparisons of the susceptibilities of planktonic and adherent Candida albicans to antifungal agents: a modified XTT tetrazolium assay using synchronised C. albicans cells.

Adhesion of synchronised yeast-phase Candida albicans cells to tissue culture plastic, and the susceptibility of planktonic and adherent cells to antifungal agents, was investigated using a modified tetrazolium (XTT) assay. MIC data demonstrated that ketoconazole and amphotericin B were highly active against planktonic C. albicans yeast-phase cells. XTT tetrazolium assays permitted comparisons of MIC values with XTT formazan IC50 and IC80 (percentage inhibitory concentrations); IC50 and IC80 values for amphotericin B and ketoconazole were similar. Furthermore, IC50 and IC80 values for 24 h incubation with antifungal agent were typically higher than corresponding IC50 and IC80 values for 48 h incubation. Furthermore, in comparison to values for planktonic Candida cells, adherent cells were typically less susceptible to amphotericin B and ketoconazole. For example, with increasing incubation time following the initial adhesion period, cells became progressively less susceptible to amphotericin B and ketoconazole: 24 h (P < 0.05) and 48 h (P < 0.001). Furthermore, other azoles showed the same activities compared with ketoconazole against both planktonic and adherent cells. Overall, the data demonstrate the usefulness of the XTT tetrazolium assay in describing comparisons of the susceptibility profiles for both planktonic and adherent synchronous yeast phase C. albicans in vitro.

Amphotericin B↗

PubMedDate not supplied

Adhesion of different Candida spp. to plastic: XTT formazan determinations.

Adhesion of synchronized yeast-phase Candida cells to tissue culture plastic was investigated using the tetrazolium salt, XTT. The procedure permits the direct enumeration of adherent yeasts following the metabolic conversion of the XTT tetrazolium salt, to its reduced formazan form, by mitochondrial dehydrogenases. Using this procedure, the formation of XTT formazan by Candida cells was typically related to the inoculum size. The adhesion of Candida yeast-phase cells from different Candida spp. to plastic was of the following order: C. krusei (n = 5) > C. albicans (n = 10) > C. glabrata (n = 6). Furthermore, preliminary experiments with several other species indicated that C. tropicalis (n = 2) may adhere as well as C. albicans and that one strain each of C. guilliermondii and C. parapsilosis appear to adhere to plastic in a similar fashion to C. glabrata. The data indicate the utility of the XTT tetrazolium based assay in enumerating the adhesion of different Candida spp. to plastic.

Adhesiveness↗