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Biomedical subjects

E Drouhet

Publications and source records attributed to E Drouhet.

At least 109 records · Page 6Linked to original sources

Chronic mucocutaneous candidosis and other superficial and systemic mycoses successfully treated with ketoconazole.

Four patients with chronic mucocutaneous candidosis from early infancy were treated successfully with ketoconazole given orally. All thrush lesions were clinically and mycologically cured within a few days of treatment with 100-400 micrograms of ketoconazole daily; skin lesions were cured within a few weeks, and nails were cured after about three months of treatment. Delayed cutaneous hypersensitivity to candidin was acquired by the third month. Cellular and humoral immunologic responses were related to the suppression of Candida albicans antigen by ketoconazole. A fifth patient with chronic lingual granuloma due to C. albicans improved considerably. Favorable results also were seen in individual patients with oral and disseminated histoplasmosis due to Histoplasma capsulatum; laryngeal, pulmonary, and hepatic disease with continuous fever also due to H. capsulatum; pulmonary histoplasmosis due to Histoplasma duboisii; cutaneous sporotrichosis; and cutaneous blastomycosis due to Blastomyces dermatitidis and in three patients with favus due to Trichophyton schoenleinii; six of seven patients with tinea capitis due to Trichophyton violaceum (after one month of treatment); and four patients with infections due to Petriellidium boydii, Phialophora pedrosoi, or Beauveria species. All patients responded rapidly to 400 mg of ketoconazole per day given orally. Only the patient with hepatic histoplasmosis required 800 mg per day. Measurements of ketoconazole in the serum during treatment were useful in the evaluation of therapy.

Adolescent↗

Evolution of antifungal agents: past, present, and future.

Important progress has been achieved in antifungal chemotherapy in recent years. Two groups of drugs are now used: those produced by various organisms and those made synthetically. In the first group, only amphotericin B (1956) administered systemically is active in numerous deep mycoses. Although toxicity limits the use of amphotericin B, it is still the drug of choice for systemic mycoses. Griseofulvin was the first agent used for oral treatment of dermatophytoses. The introduction of flucytosine began a new era in chemotherapy; however, although flucytosine is orally administered and rapidly distributed, its antifungal activity is limited to cryptococcosis and systemic candidosis. The rapid induction of flucytosine-resistant mutants led to the development of treatment regimens of amphotericin B plus flucytosine. With the development of imidazole derivatives in 1969, a new generation of azole antifungal agents has emerged. Of these, only ketoconazole was orally active. New azole derivatives and triazoles have been synthesized, but only itraconazole has been successful in the treatment of superficial and deep mycoses in humans. Future trends for the development of agents with fungicidal activity, wider spectra, and better distribution are proposed. The association of immunotherapy with antifungal chemotherapy may offer new treatments for fungal infections in immunocompromised patients.

Amphotericin B↗

Early experience with itraconazole in vitro and in patients: pharmacokinetic studies and clinical results.

The efficacy of itraconazole, a new triazole antifungal agent, was studied in vitro and assessed in patients. The MICs of itraconazole for 16 strains of Aspergillus fumigatus were in the same range as those of amphotericin B: less than 0.09-0.36 microgram/ml vs. less than 0.09-0.78 microgram/ml, respectively. Eight adult patients with systemic fungal infections were treated orally with 100-200 mg of itraconazole two times a day. A patient with relapsing histoplasmosis (Histoplasma capsulatum var. duboisii) was cleared of the infection; a patient with arthritis of the knee due to Phialophora parasitica did not respond to treatment; four patients with semiinvasive pulmonary aspergillosis improved dramatically and were considered clinically cured; and two patients with aspergilloma improved. The duration of follow-up was one to nine months. Levels of itraconazole in body fluids were measured by a bioassay. Levels of drug in knee fluid were about 30% of the simultaneous levels in plasma. A progressive decrease in the level of itraconazole in plasma occurred in two patients, and a progressive increase in the levels occurred in five patients.

Adult↗

[Sensitivity and resistance of pathogenic yeasts to 5-fluoropyrimidines. I.--Relation between the phenotypes of resistance to 5-fluorocytosine, the serotype of Candida albicans and the ecology of various species of Candida of human origin (author's transl)].

The sensitivity to 5-fluorocytosine (5-FC), 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUri) of 583 strains of C. albicans of human origin shows a relationship between their ecology, their serotype and their sensitivity to 5-FC. The incidence of the primary resistant strains isolated from patients with systemic candidiasis is of 4%, and 88.8% of the resistant strains belong to serotype B. In a closed community of premature infants the only resistant isolate amongst 78 strains recovered during hospitalization also belong to the B serotype and was introduced from outside. African strains of vaginal origin showed a higher incidence (21.6%) of resistance than did the european strains (4.5%) and this resistance was related to the B serotype predominant in the African environment. This raises the problem of the structure of the cell wall in connection with the active sites, the antigenic determinants and the enzymatic equipment.

Candida↗

Sensitivity and resistance of pathogenic yeasts to 5-fluoropyrimidines. II.--Mechanisms of resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU) (author's transl).

Incorporation of labelled 14C-pyrimidines and 5-fluoropyrimidines (5-FC and 5-FU) in four different phenotypes of wild strains of Candida isolated from man showed comparable results to those obtained by the minimal inhibition concentration (MIC) test. Kinetics studies demonstrated significant rates of incorporation after 24 hours of culture in each case. It was also possible to infer the biochemical mechanisms of resistance to 5-FC, namely a defect in UMP pyrophosphorylase, cytosine deaminase and 5-FU permease in the ease of the following phenotypes: 5-FCR 5-FUR, 5-FCR 5-FUS and 5-FCS 5-FUR (R = resistant; S = sensitive). In this study, the permeation process was approached by a consumption assay which determined the rate of labelled substrates into the medium before and after 24 hours of culture. Thus, it was found that the consumption levels of the phenotype 5-FCS 5-FUS were very high, while those of the phenotype 5-FCR 5-FUR were minimal. The 5-FCS 5-FU5 phenotype had no detectable consumption of 5-FU. With regard to the 5-FC5 5-FUS phenotype, it seems that the non-incorporation of 5-FC into the RNAs after the consumption by the yeasts has a feed back effect on the permeation process.

Candida↗

[Eradication of Candida from a premature infant unit].

To eradicate Candida from a neonatal unit the authors used increasingly strigent protocols of prophylaxis and treatment. Finally all carriers were identified and treated with nystatin. A strict routine for washing hands was introduced. As a result of these measures the cross infection rate within the hospital was very low (3%). The eradication was maintained by constant surveillance (weekly oral and rectal swabs) because of regular reintroduction of Candida by babies who had been infected before transfer to the unit. The other conclusions were that post natal infection is usually due to cross infection and rarely from mother. The gut and perianal skin are important reservoirs of infection. Erythema of the buttocks almost disappeared after the eradication of Candida. Guteal erythema commonly preceded of manifestations of Leiner's disease.

Candidiasis↗