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Biomedical subjects

J Van Cutsem

Publications and source records attributed to J Van Cutsem.

87 records · Page 5Linked to original sources
PubMed1975

Bilogical and toxicological properties of econazole, a broad-spectrum antimycotic.

The spectrum of activity of 1-(2,4-dichloro-beta-[(p-chlorobenzoyl)oxy]phenethyl)imidazole-nitrate (econazole, R 14827) was tested in vitro on various pathogenic fungi and bacteria, and also in vivo in guinea-pigs and rats experimentally infected with dermatophytes and C. albicans. The in vitro activity spectrum is very broad: the dermatophytes, the yeasts, the dimorphic fungi, the aspergilli, the mycetoma causing agents and the Gram-positive bacteria being most sensitive. Guinea-pigs infected with T. mentagrophytes, M. canis or C. albicans and treated topically or orally with econazole, were cured. In each of these tests the activity of econazole was compared with that of different reference drugs. Vaginal candidiasis in rats was cured after oral administration of econazole. Toxicity and teratogenicity studies in different laboratory animals indicate that econazole is well tolerated.

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Ketoconazole in experimental candidosis.

A relatively large number of animal models of candidosis exist in which the efficacy of antifungal substances can be evaluated. These include models of candidosis of the skin, gastrointestinal tract, genital system, and internal organs in a variety of animal species. The efficacy of ketoconazole administered orally and topically was evaluated; when given orally in relatively low doses, ketoconazole was found to be efficacious in all of the experimental models used. Scanning and transmission electron micrographs of infected tissue demonstrated the rapidity with which Candida albicans was eradicated from the host after administration of ketoconazole.

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Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models.

The activity of itraconazole in vitro was evaluated for 2,094 strains of 132 fungal species, one achloric alga, nine actinomycetes, and six bacterial species. Itraconazole was active against dermatophytes (271 strains), Candida species (1,303), Cryptococcus neoformans (27), Torulopsis species (170), Pityrosporum species (40), Aspergillus species (87), Sporothrix schenckii (12), dimorphic fungi, Dematiaceae, and various other organisms. This activity depended largely on the test conditions and the medium used. Ittraconazole was as active as ketoconazole in the treatment of dermatophytoses and of both superficial and deep candidosis at oral doses about eight and four times lower, respectively, than the doses of ketoconazole required. Disseminated dermatophytosis was cured more rapidly by itraconazole than by ketoconazole. Parenteral and oral itraconazole were of equal efficacy for the treatment of systemic candidosis. Itraconazole used topically was more active than reference compounds against microsporosis, trichophytosis, and superficial candidosis. Given orally, itraconazole was effective therapy for aspergillosis and meningo-cerebral cryptococcosis in mice and for generalized cryptococcosis, histoplasmosis, and sporotrichosis in guinea pigs. No drug-related adverse effects were observed.

Administration, Oral↗
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Monoclonal antibody-gold silver staining dot assay for the detection of antigenaemia in candidosis.

A monoclonal antibody (Mab), designated 5B2, reacting with cell wall mannoproteins of Candida albicans has been purified and coupled to colloidal gold. The ability of the gold conjugated Mab to detect C. albicans antigens in serum during infection has been assessed in a dot immunobinding assay involving an immunogold silver enhancement procedure (GSS). A double blind study was made with sera from 140 guinea pigs, including 40 control animals and 100 infected intravenously with C. albicans. Sera from infected animals were collected either 2 days (4 animals), 15 days (9 animals), or 21 days (87 animals) after inoculation. The overall sensitivity, specificity and positive predictive value of the test were 89, 95, and 98%, respectively. However, differences were encountered in the ratio of positive tests in relation to duration of the infection. Mab-GSS dot immunobinding has also been applied, together with Mab co-counterimmunoelectrophoresis on successive sera from 2 patients who recovered from clinically and mycologically proven episodes of systemic candidosis. It was demonstrated that both patients synthesized antibodies against glycoproteins sharing the 5B2 epitope, which was initially present transiently in their sera.

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Oral itraconazole versus topical bifonazole treatment in experimental dermatophytosis.

Guinea pigs, infected with either Trichophyton mentagrophytes or Microsporum canis, were treated orally or topically with azole antifungals daily for two weeks. Fungi located in the stratum corneum were affected similarly by both treatment schedules, showing typical cell wall changes after azole exposure and necrosis of internal organelles. Fungi located in the hair sheaths were affected only by the oral treatment, which not only prevented invasion of the inner hair structures and inflammatory responses but also led to a complete clearance of the infection within 7 days. Topically applied azole treatment was not able to injure fungi in the hair sheaths and did not suppress invasion into the hair shafts. These observations are in favour of oral antifungal medication with azoles for the treatment of dermatophyte infections involving hairy skin.

Administration, Oral↗
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Therapy of experimental meningeal and disseminated cryptococcosis.

This study evaluated the efficacy of itraconazole, a broad-spectrum triazole antifungal drug, which has previously been demonstrated to exhibit activity against Candida albicans C. krusei, C. glabrata, Aspergillus, Histoplasma and Blastomyces as a potential treatment for cryptococcosis. The susceptibility of 62 strains of Cryptococcus neoformans was tested in vitro. All strains were inhibited by itraconazole 0.1 microgram ml-1. Itraconazole was fungicidal after replenishment at a concentration that can easily be achieved in vivo. When mice were infected intracerebrally with Cr. neoformans all control animals died, whereas only 11% and 26% of itraconazole-treated animals died. In a group treated with ketoconazole, 67% died. After intravenous infection, 30% of control guinea pigs died, while other animals treated with itraconazole (5 or 10 mg kg-1) or amphotericin B (1.25 or 2.5 mg kg-1) all survived. Itraconazole 10 mg kg-1 produced the best results, with brain and meningeal cultures becoming negative in 55-64% of animals. In addition, intravenously infected guinea pigs received oral or intraperitoneal treatment with itraconazole or fluconazole (each 5 or 10 mg kg-1) as monotherapy or in combination. Although both treatments were active, itraconazole 10 mg kg-1 was the most effective. In two out of six immunosuppressed guinea pigs infected with Cr. neoformans oral itraconazole was effective, resulting in negative brain and meningeal cultures. A combination of itraconazole (5 mg kg-1) with flucytosine or amphotericin B was more efficacious than monotherapy. Therefore, itraconazole is a potentially effective therapy for the treatment of Cryptococcus infection when administered either alone or in combination with other antifungal drugs. It may also be effective in immunocompromised patients.

Administration, Oral↗
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Prophylaxis of Candida and Aspergillus infections with oral administration of itraconazole.

The broad-spectrum oral triazole antifungal, itraconazole, has been shown to be effective in the treatment of superficial and systemic infections with fungi including Candida albicans, C. krusei and C. glabrata, Cryptococcus, Aspergillus, Histoplasma, Blastomyces and others. Its broad spectrum of activity, high and persistent tissue levels and favourable safety profile suggest that it may be appropriate for the prevention of opportunistic fungal infections in at-risk patients. In this study, itraconazole's prophylactic efficacy was tested against experimental models of Candida and Aspergillus infection. A single dose of 1.25 mg kg-1 or 2.5 mg kg-1, given 1 h before vaginal infection with C. albicans, protected 50% of treated rats. In systemic and disseminated candidosis, prophylaxis with itraconazole reduced both folliculitis and organ Candida content in guinea pigs. Amphotericin B was also used in this study and was found to be less efficacious than itraconazole. Itraconazole prolonged survival when administered to guinea pigs before experimental induction of systemic and invasive aspergillosis. In all cases, increasing the itraconazole dosage increased its prophylactic efficacy. Therefore, as the clinical efficacy of itraconazole is accurately reflected by the results of animal models, this study shows itraconazole to be a potential prophylactic therapy for patients at risk of opportunistic fungal infection.

Administration, Oral↗
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Experimental aspergillosis in guinea pigs: influence of itraconazole on fungaemia and invasive fungal growth.

The guinea pig model of experimental aspergillosis was used to evaluate the efficacy of itraconazole 2.5 and 5 mg kg-1 in preventing the invasive phase of the disease when animals were already loaded with Aspergillus conidia. Evaluations were made by recording the survival rates, culturing fragments of nine organs, examining seven organs by means of histochemistry and immunohistochemistry (mAb EB-A1 to Aspergillus galactomannan) and by serological titration of galactomannan. The data indicate that itraconazole is highly effective in preventing true invasive aspergillosis. Serological evaluations of antigenaemia suggest that low titres may only reflect fungaemia, while titres of 1:8 and above are suggestive of invasive disease.

Administration, Oral↗
PubMedDate not supplied

Antifungal activity of enilconazole on experimental Aspergillosis in chickens.

Day-old chickens were infected with various inoculum sizes of airborne spores of Aspergillus fumigatus, which caused high rates of mortality and morbidity. Fumigation with enilconazole smoke pellets was highly successful in preventing mortality, in reducing morbidity, and in neutralizing growth inhibition of infected chickens. No side effects were observed.

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