Laboratory and clinical assessment of ketoconazole in deep-seated mycoses.

Forty-eight cases of deep mycoses were studied and treated with ketoconazole, each with in vitro evaluation of the minimum inhibitory concentrations (MIC) of the causative fungi, in vivo pharmacokinetic, clinical, and mycologic evaluations, several months to two years after the treatment was stopped. Excellent results were obtained in six cases of chronic mucocutaneous candidiasis, with restoration of immunologic disturbances; 23 cases of systemic candidiasis, including new aspects of heroin addicts with cutaneous, ocular, or osteoarticular manifestations; eight cases of histoplasmosis, five due to Histoplasma capsulatum and three to Histoplasma duboisii, with cure in seven and remission in one; one case of African blastomycosis (Blastomyces dermatitidis); three cases of mycetoma, two due to Monosporium apiospermum, one due to a dematiacious fungus; three cases of entomophthoromycosis with cure; one case of fungal arthritis, due to new hyphomycete similar to M. apiospermum, pathogenic for laboratory animals; one case of Drechslera longirostrata causing vertebral arthritis, following a fungal endocarditis and cured by combination of ketoconazole with amphotericin B, each agent alone being ineffective; and other deep mycoses.

Yeast tissue phase of Emmonsia pasteuriana inoculated in golden hamster by intratesticular way.

The scope of our study was to present an experimental model reproducing the dimorphic yeast-like population (as for Histoplasma capsulatum, Blastomyces dermatitidis) similar to that observed in the cutaneous biopsy of an Italian woman who had never traveled abroad, being intravenous drug user and HIV positive for 10 years, finally infected with the new dimorphic fungus Emmonsia pasteuriana. Experimental inoculation was unsuccessful by intraperitoneal (i. p.) and intravenous (i. v.) ways in a mouse and in a guinea-pig model inoculated by cutaneous or subcutaneous routes, reason for that we chose the golden hamster, highly sensitive to dimorphic fungi as agents of systemic mycoses as histoplasmosis, blastomycosis, sporotrichosis, penicilliosis marneffei, paracoccidioidomycosis when the inoculation was done by intraperitoneal route. We inoculated young golden hamsters by i. p. and intratesticular ways. Only by this last route we reproduced an orchiepididymitis with necrosis, haemorrhages and a polymorphic yeast-like population similar to the polymorphism observed in the cutaneous biopsy of the patient. The intratesticular affinity of E. pasteuriana provided an interesting model for this infection.

[Ulcerative colitis caused by Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome]. / Colite ulcéreuse à "Histoplasma capsulatum" chez un patient atteint d'un syndrome d'immunodépression acquise (SIDA).

The authors report a case of ulcerative colitis due to Histoplasma capsulatum in a previously healthy 35 year-old french geologist with acquired immune deficiency syndrome (AIDS). Gomori-Grocott and PAS stains and indirect immunofluorescence revealed Histoplasma capsulatum in colonic biopsies. The search for LAV antibody was positive. T-lymphocyte analysis revealed 10/mm3 OKT4 with OKT4/OKT8 ratio of 0.16. Histoplasmosis should be considered in subjects with ulcerative colitis according to the epidemiological context. In patients with AIDS relapses after discontinuation of treatment are to be expected and suppressive therapy with an imidazole derivative should probably be continued indefinitely.

[Current status and trends in quality control in parasitology and mycology]. / Réalisations et perspectives du contrôle de qualité en parasitologie et mycologie.

The survey of the results of the control quality in Parasitology and Mycology showed in general an improvement in the correct diagnosis for the specimen analysed (preparations of parasites, smears, stools, sera, fungal cultures). The wrong diagnosis of Ascaris lumbricoides eggs in stools diminished from 5% to 1.5%. The trichrome Gomori-Wheatley stain technic on smears in PVA was introduced. 16 reference or national standards sera for the parasitological serology, including 6 for toxoplasmosis and one for candidiasis were established. The increasing number of participants (more than 4,000) and particularly for the serology of toxoplasmosis showed the interest of the biologists for the quality of their tests.

[Histoplamosis in otorhinolaryngology]. / L'histoplasmose en oto-rhino-laryngologie.

Histoplamosis is the most frequently imported tropical mycosis observed in France. Of the cases reported in the published literature, 30 to 50 p. cent present buccopharyngeal lesions as the initial symptom revealing the presence of the disease, or forming part of a form involving multiple viscera (18.6). Since the first case reported in France in a thesis by Leger (13) in 1954, other french publications, mainly from dermatologists, stomatologists, or otorhinolaryngologists, have drawn attention to these misleading, little known buccal manifestations, that are often recognized only at a late stage (1, 4, 5, 8, 9, 10, 14, 15, 16). Five new cases treated at the Pasteur Institute Hospital are reported.

[Antifungal agents in otorhinolaryngology]. / Antifongiques en oto-rhino-laryngologie.

Numerous progresses are realized in the chemotherapy of mycoses, particularly in the field of deep mycoses due to 3 categories of systemic antifungal agents: polyenes (oral nystatin, oral and intravenous amphotericin B), 5-fluorocytosine (oral and intravenous) and imidazole derivatives (oral and intravenous miconazole, oral ketoconazole). The old drugs as nystatin and amphotericin B per os continue to have a remarkable effect in oro-pharyngeal candidosis, chiefly after sufficient local contact with the mucos membranes; topical preparation are effective in fungal O.R.L. localizations (aspergillar or candidal otomycoses, glossitis). IV amphotericin B is indicated in naso-orbital-cerebral mucor mycosis, nasosinusal aspergillosis, candidosis, entomophthoromycoses and particularly systemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis) in spite of severe toxicity. 5-fluorocytosine (100-200 mg/kg) has a limited spectrum to Candida, Cryptococcus neoformans, Aspergillus fumigatus infections if the strains are sensitive to this agent (5% primary resistance). Among the new imidazole derivatives, ketoconazole (400 mg/day) represent a revolutionary antifungal agent due to a very large antifungal spectrum, absence of toxicity, rapid diffusion by oral way, and high therapeutic efficiency in candidosis, histoplasmosis, blastomycosis, rhino-entomophthoromycosis... Oral miconazole has a poor diffusion into the tissues and by intravenous way necessitates several injections daily to obtain therapeutic levels. Numerous imidazole derivatives (econazole, miconazole, clotrimazole etc...) can be successfully utilized by topical application, as well as numerous other local antifungal agents.

[Panorama of mycoses in otorhinolaryngology]. / Panorama des mycoses en oto-rhino-laryngologie.

Three classes of important mycoses in O.R.L. field can be recognized according to the responsible fungi and to thier physiopathology: 1) mycoses due to cosmopolite, opportunistic fungi, yeast-like fungi (Candida albicans, Cryptococcus neoformans, Torulopsis glabrata) or filamentous fungi (Aspergillaceae, Mucoraceae, Penicillia, etc...) invading a compromised host by antibiotics, immunosuppressors, radiotherapy or by severe diseases (hemopathia, diabetes with acidosis). The oropharyngolaryngeal candidosis, the black tongue (a polyfungal syndrome), the sinusal aspergillosis, the otomycoses, the nasalorbital cerebral form of mucormycosis are reviewed and the allergic accompanying symptoms described. 2) deep, systemic mycoses of tropical origin with respiratory entry and oral pharyngeal laryngeal metastatic localizations (histoplasmosis, blastomycosis, paracoccidioidomycosis, coccidioimycosis); the histoplasmosis represent actually the principal imported systemic mycosis with O.R.L. localization. 3) tropical and african mycosis localized exclusively in O.R.L. area (rhino-enthomophtoromycosis and rhinosporidosis).

[Mycotic lingual granuloma. The pseudotumoral form]. / Granulome lingual mycosique. Forme pseudo-tumorale.

Lingual candidiasis is a condition arising from a multiple of causes, some of which are well known (thrush, etc...). Two cases of chronic lingual mycotic granuloma are presented, one of which was due to a candida, the diagnosis being confirmed by pathological examination and electrosyneresis. The course of this granuloma leads to the appearance of a true epidermoid carcinoma, as illustrated by the description of other cases that have been reported. Current therapy for the granuloma itself mainly depends on the employ of ketoconazole, but the unfavorable course of the affection raises the question of the need for associated surgery.

[New case of rhinoentomophtoromycosis. Cure by ketoconazole]. / Nouveau cas de rhino-entomophtoromycose. Guérison par le kétoconazole.

A new case of rhino-entomophtoromycosis due to Conidiobolus coronatus is added to the ten others observed in Cameroon, among the 62 african cases described. The patient, a man 27 years old, has an elephantiasis form with nasal obstruction, hypertrophy of lips, globulous forms of cheeks, giving a monstrous facies. After failure of KI and intravenous miconazole, therapeutic success was obtained with oral ketoconazole. After improvement with 400 mg daily, the doses were increased to 600 mg to obtain mycological and clinical cure with good clinical and biological tolerance; important eosinophilia related to the destruction of the fungus was observed. Restorative surgery was necessary to render a more human aspect of the monstrous lesions of face.

[Current role of deep mycoses in infectious pathology]. / Place actuelle des mycoses profondes dans la pathologie infectieuse.

Deep mycoses present new aspects characterized by deep, visceral mycotic localisations and septicemia, particularly in immunocompromised conditions. In immunodepressed patients (leukaemia, transplantation), the granulopenia descending to 500 elements/ml leads not only to invasive aspergillosis and candidosis but also to infections due to opportunistic fungi exceptionally or never seen formerly. AIDS favours opportunistic fungi related to defective cellular immunity as Cryptococcus neoformans, responsible of severe meningoencephalitis and septicemia, as Candida albicans responsible of thrush and oesophagitis, but also true pathogenic fungi (Histoplasma capsulatum) becoming opportunistic in such conditions. C. albicans provokes in heroin addicts a new septicemic syndrome with cutaneous, ocular and osteoarticular lesions and in leukaemic patients hepatic micro-abscesses soon after the neutropenic phase induced by chemotherapy. New methods for immunologic diagnosis (research of circulating fungal antigen), for clinical diagnosis (scanning, magnetic resonance). New strategy of antifungal chemotherapy (itraconazole, fluconazole) allow to a better knowledge and control of this new infectious pathology.

[Histoplasmosis and other imported mycoses in 1989]. / Histoplasmoses et autres mycoses d'importation en 1989.

The most common systemic mycoses imported into France are the histoplasmosis caused by H. capsulatum, which comes from Black Africa and from the French overseas departments and territories (Guyane, Martinique, Guadeloupe, New Caledonia), and the histoplasmosis caused by the larger H. duboisii, which is exclusively Central African. In recent years, histoplasmosis has become an opportunistic infection in immunocompromised patients, particularly those with AIDS. Blastomycosis, imported from North America as well as from North Africa and Central Africa, and paracoccidioidomycosis, imported from Latin America, are pulmonary mycoses with cutaneous manifestations on the face and extremities and with various deep localizations which often follow a chronic course. Coccidioidomycosis, strictly limited to the desertic regions in the western part of the American continent, is also a pulmonary mycosis with multiple granulomas in the skin, bones, lymph nodes and meninges. Penicilliosis caused by Penicillium marneffei is a mycosis from South-East Asia which has recently been observed in European AIDS patients who had travelled in that part of the world.

Fluconazole in the management of oropharyngeal candidosis in a predominantly HIV antibody-positive group of patients.

Seventy-one patients with oropharyngeal candidosis received treatment with fluconazole given as a single 50 mg capsule once daily. Of these patients 61 were HIV-antibody positive. Candidosis had been present in nearly all patients for a least one month prior to fluconazole treatment. The duration of daily therapy was 5-20 days and in many cases this was followed by a period of maintenance treatment using 50 mg fluconazole every 48 h. In all 42 symptomatic patients, clinical resolution of the infection occurred within 7 days. Significantly, this included the disappearance of dysphagia in four patients with proven candidal oesophagitis. A marked reduction, or eradication of oral yeasts occurred concomitantly in virtually all patients. Fluconazole was well tolerated by all patients and there were no significant changes in haematological or hepatic parameters that could be attributed to the drug. The results suggest that fluconazole is an appropriate treatment for oropharyngeal candidosis and comparative studies with other agents should now be conducted.