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PubMed1992

Epidemiological typing methods for mycoses.

Despite the increasing importance of nosocomial fungal infections, very little is known of the epidemiology, mode of transmission, or pathogenesis of infections due to fungal pathogens. Recently, a number of potentially useful epidemiological typing systems have been employed for identification of strains within species of Candida and other fungi. Epidemiological studies employing either DNA-based or protein-based typing methods have provided some interesting insights into the epidemiology of nosocomial fungal infections, particularly nosocomial candidiasis. Careful epidemiological studies employing selected typing methods are essential to the rational development of effective measures for prevention and control of nosocomial infections caused by opportunistic fungal pathogens.

Candida↗
PubMedDate not supplied

Prevention and mycoses in immunocompromised patients.

Invasive fungal infections remain a major complication in immunocompromised hosts. The prognosis in these infections is poor, particularly for neutropenic patients with cancer. Candidiasis and aspergillosis are common in these patients, and numerous attempts have been made to evaluate potential prophylactic methods. Despite the fact that various agents (polyenes and/or imidazoles) and various formulations have been tested, the reported data on their effectiveness are still controversial. No single regimen can be recommended at this time for prevention of invasive candidiasis. The potential emergence of fungal strains resistant to the polyenes and the selection of Torulopsis glabrata by the imidazoles should also be taken into consideration. Aspergillosis, which is an airborne infection, may be prevented by isolation of patients at risk in rooms equipped with high-efficiency particulate air (HEPA) filters. In addition, the prophylactic administration of nasal sprays of amphotericin B has shown encouraging results, and this approach should be further investigated.

Administration, Topical↗
PubMedDate not supplied

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↗
PubMedDate not supplied

A clinical trial of itraconazole in the treatment of deep mycoses and leishmaniasis.

Itraconazole was administered orally to two patients with sporotrichosis, 10 patients with paracoccidioidomycosis, three with mycetomas (due to Madurella grisea, Streptomyces madurae, and Pseudochaetosphaeronema larense, respectively), nine with chromomycosis due to Cladosporium carrionii, five with chromomycosis due to Fonsecaea pedrosoi and five with leishmaniasis (including one with the nodular disseminated form). The clinical and laboratory tests showed excellent tolerance to the drug with a total absence of adverse reactions. Satisfactory results were achieved against paracoccidioidomycosis, sporotrichosis, and chromomycosis due to C. carrionii (apparent cure was achieved in a short time). Encouraging improvement was noted in the treatment of mycetoma due to M. grisea. Among the five cases of leishmaniasis, a complete clearing was achieved in one and an encouraging improvement in two, including the one with the nodular disseminated form. Two patients with F. pedrosoi infection were apparently cured after the addition of thermotherapy and flucytosine, respectively, to the treatment regimen.

Adolescent↗
PubMedDate not supplied

Initial experience in therapy for progressive mycoses with itraconazole, the first clinically studied triazole.

The search for antifungal drugs, particularly oral agents with a broad spectrum of activity, led to the study of itraconazole, a triazole. In vitro susceptibility testing suggested activity against a variety of fungal pathogens affecting humans. Pharmacokinetic studies indicated absorption after oral administration to patients, with prolonged serum concentrations and peak levels exceeding the in vitro inhibitory concentrations for most pathogens. Twenty-four patients have been enrolled in efficacy studies; two-thirds of these individuals had experienced a relapse after apparently successful therapy with other drugs, had failed to respond to other drug therapy, and/or had experienced intolerable side effects with other drugs. Fourteen patients have thus far responded to treatment with itraconazole; this group includes two persons each with coccidioidal pneumonia and adenopathy, pulmonary coccidioidomycosis, and dermatophytosis plus onychomycosis as well as one person each with coccidioidal epididymitis, adrenal histoplasmosis, head and neck histoplasmosis, cutaneous blastomycosis, oral-sinonasal alternariosis, chromoblastomycosis, invasive pulmonary aspergillosis with fungus ball, and onychomycosis. Five other patients have had partial responses to therapy, three have failed to respond, and two have been deemed unassessable. Drug toxicity has been limited in 211.8 patient-months of therapy. The results are encouraging and indicate that more extensive studies are warranted.

Adult↗
PubMedDate not supplied

Tolerance to and efficacy of itraconazole in treatment of systemic mycoses: preliminary results.

Twelve patients with mycotic infections were treated with itraconazole during a one-year period. Patients had the following conditions: coccidioidomycosis (three), histoplasmosis (three), mucocutaneous candidosis (two), aspergillosis (three), and urinary tract infection due to Torulopsis glabrata (one). The daily dose of itraconazole ranged from 100 to 200 mg. Ten of the 12 cases were assessable. Clinical improvement was observed in six patients, two with coccidioidomycosis, two with mucocutaneous candidosis, one with histoplasmosis, and one with aspergilloma. Four patients did not respond to therapy; two of these patients had aspergillosis, one had histoplasmosis, and one had T. glabrata infection. No adverse effects were attributable to itraconazole.

Adult↗
PubMed1985

Treatment of systemic mycoses with ketoconazole: in vitro susceptibilities of clinical isolates of systemic and pathogenic fungi to ketoconazole.

Ketoconazole was tested in vitro in three different media against 69 isolates of pathogenic fungi by using a macro-broth dilution procedure. The dimorphic systemic pathogens were highly susceptible, with most isolates of Blastomyces dermatitidis and Histoplasma capsulatum being inhibited and killed by concentrations less than or equal to 0.39 micrograms of ketoconazole/ml. Most isolates of Coccidioides immitis were also inhibited or killed by 0.39 micrograms of ketoconazole/ml; however, several were not killed by 100 micrograms/ml. Isolates of Cryptococcus neoformans and Sporothrix schenckii appeared to be less susceptible, with many isolates being resistant to less than or equal to 1.56 micrograms of ketoconazole/ml. There were 19 isolates of B. dermatitidis, C. immitis, and H. capsulatum recovered from 12 patients either during or following treatment with ketoconazole. Evidence for selection of secondary resistance to ketoconazole in these isolates was not observed. Results of these in vitro studies correlated poorly with the clinical responses to ketoconazole observed in the patients from whom the isolates were recovered.

Blastomyces↗
PubMed1995

Treatment of experimental systemic mycoses with BRL 49594A.

BRL 49594A (BRL) is a water soluble analogue of amphotericin B which has been developed as a polyene with efficacy similar to amphotericin B but with much reduced toxicity. BRL was prepared in 5% glucose, and was used to treat mice experimentally infected with Aspergillus fumigatus, Cryptococcus neoformans, or Histoplasma capsulatum. In the models in which BRL and amphotericin B were compared, BRL was well tolerated but was less effective than a similar regimen of amphotericin B. However, the ability to give much larger doses of BRL than tolerated with amphotericin B suggest that this drug could be an alternative to amphotericin B.

Amphotericin B↗
PubMed1998

In-vivo therapeutic efficacy in experimental murine mycoses of a new formulation of deoxycholate-amphotericin B obtained by mild heating.

Heat-induced 'superaggregation' of deoxycholate-amphotericin B (AmB-DOC, Fungizone) was shown previously to reduce the in-vitro toxicity of this antifungal agent. We compared AmB-DOC with the formulation obtained by heating the commercial form (Fungizone, Bristol Myers Squibb, Paris, France) for 20 min at 70 degrees C, in the treatment of murine infections. An improvement of antifungal activity was obtained with heated AmB-DOC formulations due to a lower toxicity which allowed the administration of higher drug doses than those achievable with the commercial preparation. Single intravenous injections of heated AmB-DOC solutions were demonstrated to be two-fold less toxic than unheated ones to healthy mice. For mice infected with Candida albicans, the maximum tolerated dose was higher with heated than with unheated AmB-DOC solutions. In the model of murine candidiasis, following a single dose of heated AmB-DOC 0.5 mg/kg, 85% of mice survived for 3 weeks, whereas at this dose the immediate toxicity of the standard formulation in infected mice restricted the therapeutic efficacy to 25% survival. Both formulations were equally effective in increasing the survival time for murine cryptococcal pneumonia and meningoencephalitis. Injection of heated AmB-DOC solutions at a dose two-fold higher than the maximal tolerated dose observed with the unheated preparation (1.2 mg/kg) increased the survival time by a factor of 1.4 in cryptococcal meningoencephalitis. These results indicate that mild heat treatment of AmB-DOC solutions could provide a simple and economical method to improve the therapeutic index of this antifungal agent by reducing its toxicity on mammalian cells.

Amphotericin B↗
PubMed2005

New agents for invasive mycoses in children.

PURPOSE OF REVIEW: Invasive fungal infections are an important cause of morbidity and mortality in immunocompromised children of all ages. This review summarizes information on new antifungal agents, including current data on their clinical use in children, as well as alternative strategies such as antifungal combination and immunomodulation therapy. RECENT FINDINGS: Novel antifungal agents, such as the echinocandins and the second-generation triazoles, were recently introduced that exhibit promising efficacy against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. These compounds are generally well tolerated and show substantial efficacy as salvage treatment and equal or even superior efficacy compared with older azoles or amphotericin B as first-line or empiric therapy for fungal infections. Clinical studies of pharmacokinetics and efficacy of the new agents in the pediatric population are, however, limited. SUMMARY: The response rates observed with the recently introduced drugs, although superior in some cases compared with older antifungal agents, are still far from satisfactory. The development of new antifungal compounds as well as the use of alternative approaches of combination therapy and immunomodulation should be pursued through well-designed laboratory and clinical studies in pediatric patients.

Antifungal Agents↗
PubMed2005

Role of new antifungal agents in prophylaxis of mycoses in high risk patients.

PURPOSE OF REVIEW: For pancreas, liver, and hematopoietic stem cell transplant recipients, no antifungal prophylaxis led to a high rate of and high morbidity from fungal infection. With the use of fluconazole as prophylaxis since the early 1990s, there have been shifts in the types of infecting fungal pathogens, documentation of resistance among fungal organisms, and changes in transplant practices. The aim of this article is to review recent clinical trials regarding antifungal chemoprophylaxis among several populations of high risk patients. RECENT FINDINGS: Itraconazole, micafungin, and posaconazole have been studied as alternatives to fluconazole prophylaxis. Itraconazole showed no dramatic improvement over fluconazole as prophylaxis during liver and hematopoietic stem cell transplantation, primarily due to gastrointestinal side effects. In addition, detrimental changes to cyclophosphamide metabolism were noted for hematopoietic stem cell transplant recipients. Micafungin was superior to fluconazole during the pre-engraftment period of hematopoietic stem cell transplantation, because it was able to prevent mold infections, required less switches to empirical antifungal therapy, and functioned as well as fluconazole in preventing yeast infections. Posaconazole was compared to fluconazole during a 16-week prophylaxis period during graft-versus-host disease, but results of this study are still forthcoming. Aerosolized amphotericin products appear to be safe for lung transplant recipients. SUMMARY: Fluconazole remains the standard agent for prophylaxis against invasive fungal infections for pancreas, liver, and hematopoietic stem cell transplant recipients. Micafungin is superior to fluconazole with minimal toxicity for use in the pre-engraftment period of hematopoietic stem cell transplantation. The optimal agent for prophylaxis later following transplant, if mold coverage is desired during prolonged immunosuppression, has not been determined.

Antifungal Agents↗