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Biomedical subjects

J Van Cutsem

Publications and source records attributed to J Van Cutsem.

At least 55 records · Page 3Linked to original sources

[Anti-Candida activity of azoles].

The in vitro activity of the broad-spectrum antifungals miconazole, ketoconazole and itraconazole was evaluated by the decimal dilution method in liquid media, for respectively 2511, 1536 and 1859 strains of yeasts belonging to 31 species. Sabouraud broth was used for miconazole and brain heart infusion broth for ketoconazole and itraconazole. These three azoles proved to be potent anti-yeast compounds. Activity by oral treatment of miconazole, ketoconazole and itraconazole was compared in gastro-intestinal candidosis of the guinea-pig, in vaginal candidosis of the rat and in systemic candidosis of the guinea-pig. Ketoconazole and itraconazole are more efficacious than miconazole in gastro-intestinal candidosis. Miconazole showed marginal activity in the other two experimental models: the spectrum of activity of miconazole was a lead for research which resulted in the synthesis and selection of ketoconazole and itraconazole. Ketoconazole was highly active in these experimental models. Itraconazole cured the animals at distinctly lower doses. No side-effects due to these azoles were observed during these experiments. A proposal is made to classify the broad-spectrum azoles in three classes: compounds for topical use (e.g. miconazole), compounds with oral activity without activity in aspergillosis (e.g. ketoconazole), compounds with oral activity including activity in aspergillosis (e.g. itraconazole).

Animals↗

Effects of ketoconazole and itraconazole on growth and sterol synthesis in Pityrosporum ovale.

The effects of ketoconazole and itraconazole on growth and sterolsynthesis in Pityrosporum ovale was studied. Itraconazole was at least 10 times more active than ketoconazole. Sterol synthesis was inhibited more rapidly than growth, suggesting that the antifungal activity of both azoles originates from an effect on the 14 alpha demethylase system, as seen in other species.

Antifungal Agents↗

Anticandidal activities of terconazole, a broad-spectrum antimycotic.

Terconazole is a new triazole ketal derivative with broad-spectrum in vitro and in vivo antifungal activities. This study further characterizes the effects of terconazole in vitro on yeast cell growth, viability, and morphology. Terconazole inhibited the growth of Candida albicans ATCC 44859 in a concentration-related manner, but with modest effects noted at levels from 10(-8) to 10(-5) M when the yeast was grown on media favoring the cell form. The inhibitory potency of terconazole on yeast cell viability varied with the strain and species of Candida tested. The susceptibility of C. albicans ATCC 44859 to terconazole was markedly enhanced when the yeast was grown on Eagle minimum essential medium, which favors mycelium formation. The effects of terconazole on the morphology of yeast cells (grown on Eagle minimum essential medium) were shown by phase-contrast and electron microscopy. There is a progression of changes, from loss of mycelia formation at 10(-8) M terconazole through complete necrosis at 10(-4) M.

Antifungal Agents↗

Azole resistance in Candida albicans.

An isolate of Candida albicans from a patient with chronic mucocutaneous candidosis who relapsed during ketoconazole treatment was compared with a number of other azole-sensitive and azole-resistant isolates by tests in vitro and in three animal models of vaginal or disseminated infection. In-vitro tests indicated that the isolate was cross-resistant to all imidazole and triazole antifungals tested. In the animal models, treatment with miconazole, ketoconazole, itraconazole or fluconazole failed to influence the infection.

Adult↗

The growth-promoting activity of vaginal fluid for Candida albicans (and the problem of enhanced susceptibility to vaginal candidosis).

Fluid aspirated from the vagina of pregnant or non-pregnant women, either normally menstruating or using hormonal contraceptives, proved to be an adequate culture medium for Candida albicans. The growth-promoting activity did not differ between groups. A medical history of vaginal candidosis did not influence this growth-promoting activity. It is concluded that an enhanced susceptibility to this manifestation with C. albicans is not related to this capacity of the fluid contained in the vaginal cavity to serve as a growth-promoting medium.

Body Fluids↗

The influence of antibiotics on the growth of Candida albicans in the vagina: an experiment with vaginal fluid.

The growth of Candida albicans in fluid aspirated from the vagina of 18 women was studied. The growth of C. albicans in the aspirated vaginal fluid to which antibiotics were added proved to be enhanced in 16 out of 18 samples. The growth of C. albicans in Sabouraud medium proved not to be enhanced by the addition of antibiotics. Dilution of the Sabouraud broth and the reduction of the amount of added antibiotics did not change the outcome. It is concluded that enhancement of the growth of C. albicans in the vagina is not due to a direct growth-promoting effect of the antibiotics on the yeast. It is concluded that most probably the growth-promoting effect of antibiotics is obtained by way of an eradication of the bacterial flora harboured in the vagina.

Adult↗

Oral treatment with ketoconazole in systemic candidosis of guinea-pigs: microbiology, hematology and histopathology.

Non-pretreated Albino guinea-pigs were infected intravenously with Candida albicans and treated orally either with placebo or ketoconazole. The 17-day follow-up of the fungal dissemination was based upon hematology, on gross and microscopic lesions and on the demonstration of the fungus by culture techniques. The efficacy of ketoconazole, both with regard to the quantity and the morphology of fungi in various organs and the tissue-healing process are discussed. The treatment of human systemic candidosis will also be considered. No side-effects due to the therapy were observed in these experiments.

Administration, Oral↗

Primary cutaneous cryptococcosis.

A 53-year-old man, a pigeon fancier, with long-standing asthma, treated for years with systemic corticosteroids, developed a fast-growing mass on his right wrist. The diagnosis of cryptococcosis was established by histology and culture of tissue which yielded Cryptococcus neoformans. Oral treatment with ketoconazole for 3 months resulted in a complete cure with residual hyperpigmentation and minute scars. During a 10-month follow-up, the patient was free of recurrences.

Animals↗

Histopathology of experimental systemic candidosis in guinea-pigs.

Unpretreated Albino guinea-pigs were infected intravenously with Candida albicans. Cutaneous candidosis with (pseudo-) hyphal outgrowth in the hair shafts and in the keratinized layers of the epidermis developed as a consequence of systemic dissemination. The spread of the infection was followed by cultures and by gross- and micropathological study of various organs of different animals during a follow-up period of 35 days. The possible relationship of organ invasion by C. albicans and skin candidosis is discussed.

Animals↗

Experimental systemic dermatophytosis.

Albino guinea pigs with abraded skin were inoculated cutaneously with 27 strains of dermatophytes from animals and humans. The same strains were inoculated i.v. in guinea pigs with intact skin. Zoophilic dermatophytes and human isolates of Trichophyton mentagrophytes var. granulare produced ringworm after cutaneous application. After i.v. inoculation, the fungus was reisolated from skin samples from a considerable number of animals with and without clinical ringworm lesions, and also from lungs, liver, and kidneys. In the lungs, hyphal aggregates were noted. Some strains produced generalized dermatophytosis affecting all parts of the skin and internal organs. T. mentagrophytes B32663, selected for further study, was inoculated i.v. in the guinea pig, rabbit, rat, mouse, and chicken. Ringworm lesions occurred in the guinea pig and rabbit; in the mouse, rat, and chicken other organs were involved. Administration by other routes did not produce a generalized infection. The infection was not self-limited and the deep-seated lesions may be responsible for the recurrence of infection.

Animals↗

Itraconazole, a new triazole that is orally active in aspergillosis.

Itraconazole is a new orally active triazole derivative with broad-spectrum antifungal activity. This drug is effective in experimental aspergillosis and possesses in vitro activity against various species and strains of Aspergillus. Morphological destruction of inoculated hyphae and complete inhibition of hyphal outgrowth in culture is obtained from 0.07 micrograms ml-1 (10(-7)M) onward. These properties make itraconazole a likely candidate for clinical evaluation in disseminated aspergillosis.

Administration, Oral↗

The antifungal activity of ketoconazole.

The antifungal properties of ketoconazole were investigated both in vitro and in vivo. The antifungal potency of ketoconazole in vitro was studied in Sabouraud's broth for 715 fungal strains belonging to 85 species and several strains were tested in other media, including Eagle's minimal essential medium. Ketoconazole is highly active in vitro and possesses broadspectrum activity. Its in vitro activity is largely dependent on the medium used. Ketoconazole's activity is increased in medium enriched with serum and in Eagle's minimal essential medium. Ketoconazole is very potent in the topical treatment of skin dermatophytosis, skin candidiasis, and in vaginal candidiasis of laboratory animals. Ketoconazole is superior to griseofulvin in the oral treatment of skin dermatophytosis. Furthermore, ketoconazole is orally highly active in skin candidiasis in guinea pigs, in vaginal candidiasis in rats, and in gastrointestinal candidiasis in various animal animal species. In systemic candidiasis and in disseminated dermatophytosis in guinea pigs cure with oral ketoconazole is achieved. No side effects are observed.

Administration, Oral↗