In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study.

Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest and compared with those of amphotericin B, itraconazole and fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.

[Epidemiology of tinea capitis]. / Epidémiologie des teignes du cuir chevelu.

PREDOMINANT IN CHILDREN: Tinea capitis is the most frequent fungal infection in children under the age of puberty. It occurs only rarely in men but is observed in adult women. Human-to-human, animal-to-human and soil-to-human transmission can be involved. HISTORICAL BACKGROUND: The spectrum of fungal species known to cause tinea capitis has steadily grown for more than a century, varying with the local urban or rural environment. Since the beginning of the 20th century and up to the advent of griseofulvin in the sixties, M. audouinii, an anthropophilic species, caused major epidemics in France, England and the USA. In the sixties to eighties, M. canis was the cause of most cases observed throughout the world. Over the last 20 years, anthropophilic species have again become the leading cause of tinea capitis epidemics, particularly in large cities, in relationship with immigration: T. tonsuransi in the USA and England and T. soudanense and M. langeronii in France. HYGIENE AND EDUCATION: Despite the benign curable nature of the disease, interhuman transmission of tinea capitis is nevertheless a considerable public health problem due to the increasing number of children affected and the risk of contagion in schools. The considerations resulting from recent studies point out the fact that transmission occurs more often in the family than the school setting, particularly indirectly by common use of grooming instruments. This would explain the high percentage of tinea capitis in large immigrant families where hair combing habits favor transmission. In France, these observations should lead to a revision of the current regulations concerning expulsion from school of children affected by tinea capitis. Better education would be a more appropriate response to the problem.

[Subcutaneous mycosis due to Scopulariopsis brevicaulis in an immunocompromised patient]. / Mycose sous-cutanée à Scopulariopsis brevicaulis chez un malade immunodéprimé

BACKGROUND: Scopulariopsis brevicaulis is a causal agent of onchomycosis. We report the unusual clinical manifestations caused by this opportunist fungus. CASE REPORT: A 61-year-old man consulted in February 1997 for a budding lesion located on the right medial malleolus. This patient had had a liver transplantation for primary biliary cirrhosis in 1990 and had been taking prednisone and cyclosporine since this time. Cyclosporine had been recently replaced by tacrolimus. The histology examination of a lesion specimen taken from the ankle evidenced a dermal mycosis due to opportunist filamentous fungus. Total excision was performed. The patient then developed nodular lesions of the left elbow during the summer of 1997. Mycology culture of a skin biopsy grew numerous colonies of Scopulariopsis brevicaulis. Excision of the elbow lesion was delayed due to hospitalization for suspected graft rejection and development of insulin-dependent diabetes. The elbow lesion was then resected followed by a skin graft. The mycology examination identified the same causal agent. DISCUSSION: This liver transplant recipient developed two unusual extra-ungual localizations (ankle and elbow) of a Scopulariopsis brevicaulis infection. Chronic immunosuppression favored development of the infection with a pseudo-epithéliomatous presentation. The histology and mycology examinations were necessary for positive diagnosis.

A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region.

In view of recent advances in the development of antifungal agents, this study examined the possible synergy of two new antifungal agents, terbinafine and amorolfine. The study compared two different courses of terbinafine treatment combined with amorolfine 5% solution nail lacquer. Terbinafine was given orally for 6 (AT6 group) or 12 weeks (AT12 group) and amorolfine nail lacquer applied weekly for 15 months. A control group received terbinafine alone for 12 weeks. This was a randomized, prospective, open study of severe dermatophyte toenail onychomycosis with matrix region involvement. Nail samples were taken before the start of the study, at inclusion and at the visits at 6 weeks, 3, 9, 15 and 18 months. To assess the value of such combined therapy we chose an early parameter as the principal outcome variable, which was the result of mycological examination, including direct microscopy and culture, at 3 months (allowing a margin of 15 days). The secondary parameters of success were the mycological results at the later visits, clinical evaluation and a combined mycological-clinical response. Safety and tolerance were also assessed. Adverse events were recorded and liver function tests were performed monthly during the terbinafine treatment. Of the 147 patients included in the trial, 121 attended the 3-month visit, within a time limit of 15 days of 3 months after the beginning of treatment: 40 in the AT6 group, 40 in the AT12 group and 41 in the control group. In all, 32 of 121 patients (26. 4%) had negative mycological results on direct microscopy and culture: 14 of 40 (35.0%) in the AT6 group, 11 of 40 (27.5%) in the AT12 group and seven of 41 (17.1%) in the control group. The cure rate for the global (mycological and clinical cure) response measured at 18 months in 145 patients was 44.0% (22 patients) in the AT6 group, 72.3% (34 patients) in the AT12 group and 37.5% (18 patients) in the terbinafine group. These results suggest that the combination of amorolfine and terbinafine may be of value in the treatment of severe onychomycosis. At the same time a pilot pharmacoeconomic analysis was performed demonstrating a better cost per cure ratio for the patients receiving combination treatment.

Recurrent subcutaneous infection due to Scopulariopsis brevicaulis in a liver transplant recipient.

We describe a case of recurrent Scopulariopsis brevicaulis subcutaneous infection, which occurred 6 years after the patient underwent liver transplantation. Combined surgery and long-term oral therapy with terbinafine resulted in a favorable outcome, although this is not the rule in the previously reported S. brevicaulis infections in immunocompromised patients.

[Familial chronic mucocutaneous candidiasis associated with autoimmune polyendocrinopathy. Treatment with fluconazole: 3 cases]. / Candidose mucocutanée chronique familiale associée à une polyendocrinopathie autoimmune. Traitement par le fluconazole: 3 cas.

BACKGROUND: Familial candidiasis endocrinopathy is a hereditary disease variably associated with i) a dysfunction of the parthyroid, adrenal, thyroid, pituitary or ovarian glands as well as the pancreas (diabetes), liver (hepatitis) and gastric wall cells (Biermer's disease); ii) chronic mucocutaneous candidiasis; iii) autoimmune manifestations: chronic keratitis, pelade, vitiligo, hemolytic anemia. CASE REPORTS: We cared for three pediatric patients with chronic mucocutaneous candidiasis associated with an autoimmune polyendocrinopathy. There was a familial context in all cases with an autosomal dominant inheritance in the first case and an autosomal recessive inheritance in the two others who were siblings. In all three cases, the chronic mucocutaneous candidiasis began before the age of 5 years and had preceded the development of the endocrinopathy. Fluconazole was effective in all three cases. DISCUSSION: Chronic mucocutaneous candidiasis may appear as the inaugural symptom of an autoimmune polyendocrinopathy and should lead to a familial study with an andocrinology work-up to determine any clinical manifestations and biological evidence of autoimmunity. Fluconazole does not have marketing approval for children, but provides good control of the fungal infection, particularly in the ungueal localization, and is well tolerated.

[Disseminated aspergillosis in acute leukemia probably chemically-induced]. / Aspergillose disséminée au cours d'une leucémie aiguë probablement chimio-induite.

One case of invasive aspergillosis in patient with myeloblastic leukemia probably induced by chimiotherapy is reported. Aspergillosis is a severe infection in immunodepressed host with 70 to 80% of mortality. Early diagnosis can be often carried by broncho-alveolar lavage, route of entry is always pulmonary one. Rapidly established antimycotic treatment can avoid death. Laminar air flow rooms and air spores numeration allow prevention of this infection in the immunodepressed host.

Diagnostic yield of bronchoalveolar lavage in pneumonitis occurring after allogeneic bone marrow transplantation.

Fifty-two bronchoalveolar lavages (BAL) were performed in order to investigate 46 episodes of pneumonitis that occurred after allogeneic bone-marrow transplantation. No complications have been attributed to this procedure. A specific etiologic diagnosis was obtained in 24 of 46 episodes (52%) by 26 of 52 BAL (50%). Cytomegalovirus (CMV), diagnosed by the presence of typical inclusions, was the pathogen most frequently identified by BAL (13 of 46 episodes) and was associated with other causes of pneumonia in 4 patients. The other causes of pneumonitis diagnosed by BAL were: giant-cell pneumonia: 1, aspergillosis alone: 3, Pneumocystis carinii: 1, Hemophilus influenzae: 3, isolated pulmonary hemorrhage: 3. One false negative (aspergillosis, n = 1) was diagnosed at autopsy. The overall mortality rate of these episodes was 24%. Thus, BAL appears to be a rapid and reproducible diagnostic method for monitoring pneumonitis in grafted patients, particularly CMV pneumonitis, and may avoid the need for surgical biopsy.

[Acquired immunodeficiency syndrome, Kaposi's disease and cerebral toxoplasmosis in a young man. Review of the literature apropos of a case]. / Syndrome d'immunodéficience acquise, maladie de Kaposi et toxoplasmose cérébrale chez un homme jeune. Revue de la littérature à propos d'un cas.

We report a new case of acquired immune-deficiency syndrome (AIDS) in a 43 year-old white homosexual man, characterized by the association of disseminated cutaneo-mucous Kaposi's sarcoma and cerebral toxoplasmosis. This man had Kaposi's sarcoma for about 10 years but evolution became quickly extensive in July 1981. Chlorambucil was prescribed at that time and was the cause of a pancytopenia. Death occurred in July 1982 due to a cerebral mass identified as toxoplasmosis on a left temporal biopsy. This observation is typical of AIDS, a new syndrome which suddenly developed in the last 2 years in the United States in homosexual men, Haitians and hemophiliacs, and is characterized by disseminated Kaposi's sarcoma and/or opportunistic infections, with a very high mortality rate. Severe toxoplasmosis of CNS has been reported in AIDS and appears to result from defects in cellular immunity which permit recrudescence of latent infection. Cerebral biopsy is necessary for the diagnosis of cerebral toxoplasmosis as seroconversion occurs infrequently in immuno-suppressed hosts. AIDS appeared in Western Europe in 1982. Most of the cases were reported in France, Denmark, Belgium and Great Britain. These cases differ from reported cases in the USA: fewer drug or poppers users, fewer homosexual men, an important number of people having lived or travelled in the Kaposi's endemic area (Mediterranean basin and Central Africa). The immunological profile of patients presenting AIDS in Europe doesn't seem to differ from the american profile: serious cellular immunodeficiency and marked increase in the suppressor/cytotoxic cell population. As in the United States, one may suspect, among several hypotheses, that it is caused by one or several transmissible agents now present in France. The nature of these agents, transmissible by sexual contacts and blood, is not yet known: the role of the CMV is now less probable and most of the studies look for the role of other factors such as the HTLV.