Molecular epidemiology of Fonsecaea pedrosoi using mitochondrial DNA analysis.

Restriction fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA) from 49 clinical Fonsecaea pedrosoi isolates (18 isolates from Japan, 17 from Madagascar, 7 from Argentina, 5 from Venezuela, 1 from Costa Rica and 1 unknown) was studied. The 49 isolates were composed of 20 isolates of Type 1, 16 of Type 2, 12 of Type 4 and 1 of a new mtDNA type, Type 7, which was closely related to Type 2. On the bases of the results of 120 isolates of the present (49 isolates) and previous (71 isolates) studies, F. pedrosoi was classified into seven mtDNA types and according to the relationship between mtDNA types and geographic origins: in Japan and probably in China, Type 1 isolates; in Zaire and Madagascar, Type 2; in Central and South America, Type 4 and Type 1. These results indicated that the geographical origin of F. pedrosoi isolate could be roughly inferred from its mtDNA type.

Safety and efficacy of single-dose fluconazole compared with a 7-day regimen of itraconazole in the treatment of AIDS-related oropharyngeal candidiasis.

The primary aim of this study was to compare the efficacy and safety of single-dose fluconazole and a 7-day regimen of itraconazole for the treatment of oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients. In this open-label trial, 40 HIV-positive patients with oropharyngeal candidiasis were randomized to receive either one dose of fluconazole 150 mg or seven daily doses of itraconazole 100 mg. Clinical condition was assessed at baseline, day 8, and day 30 (follow-up). In the fluconazole group, 15 of 20 (75%) patients were clinically cured on day 8, three (15%) were clinically improved, and two (10%) were treatment failures. At follow-up, six (30%) patients experienced relapse. In the itraconazole group, four of 17 (24%) patients were clinically cured at 8 days, and two (12%) were clinically improved; two patients relapsed by day 30. Ten (50%) patients in the itraconazole group were taking concomitant medications that could potentially affect the bioavailability of itraconazole. After excluding the results from these patients, clinical response rates remained significantly higher in the fluconazole treatment arm. These results suggest that a single 150-mg dose of fluconazole may be a safe, effective, and convenient therapy for acquired immune deficiency syndrome-related oropharyngeal candidiasis. The lower response rate in the patients who received itraconazole 100 mg daily for 7 days could be explained by drug interactions and the unpredictable absorption of itraconazole.

Twelve weeks of continuous oral therapy for toenail onychomycosis caused by dermatophytes: a double-blind comparative trial of terbinafine 250 mg/day versus itraconazole 200 mg/day.

BACKGROUND: Dermatophyte infections of the toenail have been difficult to treat, requiring long courses of therapy and having high recurrence rates. New oral antifungal agents with better outcomes and minimal adverse events are needed. OBJECTIVE: The purpose of this study was to compare two newer antifungal compounds, terbinafine and itraconazole, for efficacy and safety in toenail onychomycosis caused by dermatophytes. METHODS: The study was randomized and double-blind. It compared 12 weeks of continuous oral treatment with terbinafine 250 mg/day or itraconazole 200 mg/day for confirmed toenail dermatophyte onychomycosis. Clinical symptoms and mycologic outcome were assessed at weeks 4, 8, 12, 24, 36, and 48. A total of 372 patients (186 in each group) with dermatophyte infection confirmed by microscopy and culture were included in the intent-to-treat analysis. RESULTS: At week 48, a statistically significantly greater percentage of the terbinafine group than itraconazole group showed negative mycology (73% [119 of 163] vs 45.8% [77 of 168]; p < 0.0001) (difference = 27.2%; 95% CI = [17.0%, 37.3%]). The difference was also confirmed clinically (p = 0.001) in the patients who were clinically cured or had only minimal symptoms at the end of the study (76.2% [125 of 164] vs 58.1% [100 of 172]) (difference = 18.1%; 95% CI = [8.24%, 27.9%]). The geometric mean length of healthy nail of the big toe was significantly greater in the terbinafine than itraconazole group (8.1 vs 6.4 mm; p = 0.026). Tolerability was good to very good in almost 90% of patients in both groups, and all reported adverse events were known for these compounds. CONCLUSION: Terbinafine produced higher rates of clinical and mycologic cure at follow-up than did itraconazole.

A 12-week treatment for dermatophyte toe onychomycosis: terbinafine 250 mg/day vs. itraconazole 200 mg/day--a double-blind comparative trial.

Lamisil (terbinafine) 250 mg daily and itraconazole 200 mg daily were compared in the treatment of dermatophyte toe onychomycosis over 12 weeks in a double-blind randomized clinical trial. At the end of follow-up (week 48) treatment with Lamisil led to negative mycology in 73% of patients compared with 45.8% in the itraconazole group (P < 0.0001). Globally the clinical symptoms of the target nail improved, a response which was in favour of Lamisil (P = 0.001). The percentages of patients who were clinically totally cured or who presented with only minimal symptoms were 76.3% for the Lamisil-treated group compared with 58.1% in the itraconazole group. The unaffected nail length for big toes was significantly higher in the Lamisil-treated group (9.1 mm vs. 7.7 mm; P = 0.0298). Onycholysis was also less in the Lamisil group (P = 0.001). We conclude that 12 weeks' continuous oral therapy leads to higher cure rates with Lamisil than with itraconazole and that both drugs are equally well tolerated.

Susceptibility of clinical isolates of Fusarium to antifungal drugs.

The inhibitory activities of amphotericin B, fluconazole, itraconazole, miconazole, ketoconazole and terbinafine against nine isolates from clinically apparent infections of Fusarium solani, four isolates of Fusarium moniliforme and 10 isolates of Fusarium oxysporum were determined with an agar diffusion method (Neosensitabs) and an agar dilution method. The inhibition zones obtained with antifungal Neosensitabs need very careful interpretation. We did not find a good correlation between the agar diffusion method using Neo-sensitabs preloaded with azoles and amphotericin B and the agar dilution method. Amphotericin B (12/23) and terbinafine (18/23) showed good activity. Miconazole (7/23) and ketoconazole (3/23) had poor inhibitory activity. Fluconazole and itraconazole (0/23) had no in vitro activity against any of the isolates tested.

Further studies on the in vitro antifungal activity of amorolfine.

Minimal inhibitory concentrations (MICs) of amorolfine for 52 pathogenic yeasts or yeast-like organisms, filamentous and dimorphic fungi represented by 955 isolates were determined in agar dilution tests. Amorolfine has a broad antifungal spectrum, but unfortunately this drug is so far only available for topical use.

Cryptococcus neoformans var. gattii can be separated from var. neoformans by its ability to assimilate D-tryptophan.

An additional test to differentiate the varieties of Cryptococcus neoformans is described. It is based on the assimilation of D-tryptophan by the variety gattii.

Effects of recombinant human granulocyte-colony stimulating factor on neutropenic mice infected with Candida albicans: acceleration of recovery from neutropenia and potentiation of anti-C. albicans resistance.

The treatment of systemic candidal infection in neutropenic patients continues to be a major problem, and only 20% of patients survive despite treatment with amphotericin B (Amph B). Granulocyte colony-stimulating factor (G-CSF) is a haemopoietic glycoprotein that appears to control the survival, cycle, activation, proliferation and maturation of neutrophil granulocytes and promoter recovery from neutropenia. Confirming previous results, we observed that subcutaneous (s.c.) injection of recombinant human (rh) G-CSF in mice (30 micrograms kg-1 daily) increased the circulating leucocyte count (fourfold) on day 5 of treatment, and led to an expansion of the bone marrow myeloid compartment. The in vivo effect of rhG-CSF on murine resistance to systemic Candida albicans infection was also studied in neutropenic mice. Neutropenia was induced by intraperitoneal injection of a single dose of cyclophosphamide (CPA, 200 mg kg-1) 4 days before C. albicans infection and 2 days before rhG-CSF treatment. rhG-CSF administration showed a protective role on mice infected intravenously (i.v.) with one million C. albicans spores; all the untreated control mice died within 8 days after infection, whereas about 40% of mice treated with rhG-CSF remained alive for the same period. Furthermore, the survival rate was greater in host animals treated with combined Amph B and rhG-CSF than in those treated with Amph B alone. The number of C. albicans colony-forming units (CFU-C. albicans) in the kidney of infected mice was lower in the rhG-CSF-treated group than in the non-treated control mice. This suggests that the severity of infection is decreased in rhG-CSF-treated host animals.

Identification of the perfect state of Cryptococcus neoformans from 195 clinical isolates including 84 from AIDS patients.

Filobasidiella neoformans is the teleomorphic state of Cryptococcus neoformans and it is a heterothalic. The purpose of this study was to establish the proportions of each mating types (a, alpha) from among 195 strains of C. neoformans isolated from clinical material. The culture medium used was sunflower agar. Cultures were incubated at 20-22 degrees C for 15 days and observed periodically for one month. Non-reactive strains were mated several times with different reactive strains. Under these conditions 96.8% of the strains were found to be reactors. Among both varieties of C. neoformans, mating type alpha was found to have the highest frequency of 95% in the variety neoformans and 84% in the variety gattii. These results showed a higher reactivity in comparison with other investigators. This difference could be due to the medium used or to repeated mating with different reactive tested strains.

Onychomycoses due to Microascus cirrosus (syn. M. desmosporus).

Microascus cirrosus is very rarely the aetiological agent of onychomycosis. We report two additional cases of toenail infections caused by this fungus.

Microsporum gypseum complex in man and animals.

Twenty-eight strains of the Microsporum gypseum complex isolated from humans and animals were studied. The perfect form was found for 25 of the isolates. Nannizzia incurvata was the species most frequently involved in human pathology, while Nannizzia gypsea was most frequently found on animal lesions. Nannizzia fulva was rarely involved pathologically and Nannizzia corniculata was not isolated during this study. It is surprising to note that this species was not found even though most of our strains (22/28) came from Africa. Reliable methods are not available for differentiating among the anamorphs, which are commonly called M. gypseum, Microsporum fulvum or Microsporum boullardii. The Sabouraud medium conventionally used for medical mycology makes almost no distinction among them. We found that the species could be easily distinguished by colonial and microscopic features when grown on Takashio medium. When strains are atypical, sexual reproduction remains the reference technique but, in most cases, Takashio medium makes it possible to avoid this long drawn-out procedure.

Contribution to our knowledge of Trichophyton megninii.

In addition to its requirement for histidine, Trichophyton megninii can be readily differentiated from certain other dermatophytes, particularly Trichophyton rubrum, by its "+" mating type and a positive urease test on urea-indole broth.

The value of cryptococcal serum antigen screening among HIV-positive/AIDS patients in Kinshasa, Zaire.

Cryptococcal meningitis is a frequently observed opportunistic infection in AIDS patients in Zaire and other countries in Central Africa. The prognosis in those patients is very poor because of the advanced stage of their cryptococcal disease at presentation. To improve the prognosis of cryptococcal meningitis in HIV-infected patients through earlier diagnosis, a routine serum cryptococcal antigen screening was performed on 450 HIV-positive/AIDS patients seen at the Cliniques Universitaires de Kinshasa between 1 January 1988 and 31 August 1988. Cryptococcal antigen was detected in the sera of 55 (12.2%) of them. Cerebrospinal fluid was obtained from 44 of these 55 patients and the presence of Cryptococcus neoformans was demonstrated by direct microscopy and culture in 29 (66%) of them.

PIP: A routine serum cryptococcal antigen screening of 450 human immunodeficiency virus (HIV)-positive/acquired immunodeficiency syndrome (AIDS) patients at the Cliniques Universitaires de Kinshasa, Zaire, revealed that cryptococcal antigen was present in the sera of 55 (12.2%) of them. Health professionals collected cerebrospinal fluid of 44 patients from the positive serum group. The fungus Cryptococcus neoformans was identified by direct microscopy and culture in 29 (66%) of them. 6.6% of the originally screened HIV-positive/AIDS patients, therefore, had cryptococcal meningitis which is an opportunistic infection in these individuals. Serum screening for cryptococcal antigens could improve the prognosis of cryptococcal meningitis in HIV-infected patients by introducing an appropriate antifungal treatment at an early stage.

The role of desferrioxamine in dialysis-associated mucormycosis: report of three cases and review of the literature.

We report 3 patients on maintenance hemodialysis who developed a fulminant, disseminated and fatal form of mucormycosis. The diagnosis was made by microscopy and culture in 1 case, yielding Rhizopus rhizopodiformis, and by post-mortem microscopy in the two other cases. These patients were receiving desferrioxamine (DFO) for aluminum overload and had no iron-overload. Ten similar patients, all (with only one possible exception) receiving DFO, have been reported from American centers. The mechanism by which DFO could precipitate mucormycosis is unsettled. The explanation might be that DFO acts as a siderophore to the Mucorales fungi. High serum levels of DFO in renal failure could enhance this mechanism. Epidemiological data, provided from an inquiry in 25 Flemish dialysis centers, support the association between DFO treatment and dialysis-associated mucormycosis.