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At least 217 records · Page 12Linked to original sources

Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies.

The efficacy of oral itraconazole 2 x 200 mg capsules daily for prevention of systemic mycoses was investigated in granulocytopenic patients with haematological malignancies. Of 241 patients, 197 were evaluable for prophylactic efficacy, and 214 for adverse events. Patients with similar characteristics receiving oral amphotericin B as antifungal prophylaxis, observed over 15 months before introduction of itraconazole, served as control group (n = 223). With itraconazole prophylaxis, 13 cases of aspergillosis (9 proven, 1 probable, 3 possible; 7%) and no systemic yeast infection occurred, compared with 14 episodes of aspergillosis (9 proven, 2 probable, 3 possible; 6%) and 3 proven systemic yeast infections (Candida albicans, Candida norvegensis, Trichosporon beigelii) in the historical group. Adverse events were observed in 13% of evaluable patients receiving itraconazole. In four patients with acute lymphoblastic leukaemia receiving itraconazole and vincristine simultaneously, severe vinca alkaloid-induced neurotoxicity occurred. Plasma concentrations of itraconazole and hydroxyitraconazole were measured in 64 patients. After eight days of itraconazole the median drug concentration was adequate (700 ng/mL), but there was a marked individual variation (229-2861 ng/mL). In comparison with a historical group, antifungal prophylaxis with itraconazole reduced the incidence of systemic yeast infections, but the frequency of aspergillosis was similar. However, a general increasing incidence of aspergillus infections at our hospital over the last four years should be considered in the assessment of study results.

Administration, Oral↗

Antifungal attributes of immunosuppressive agents: new paradigms in management and elucidating the pathophysiologic basis of opportunistic mycoses in organ transplant recipients.

The currently available immunosuppressive agents cyclosporine A, tacrolimus, and rapamycin have potent antifungal activity against a number of opportunistic fungi in organ transplant recipients, most notably, C. neoformans, Candida, and Aspergillus species. The targets of their antifungal activity are fungal homologs of the signaling molecules that mediate their immunosuppressive action in humans, which has implications for further unraveling the pathogenesis of these infections. Corroborative clinical data suggest that despite the apparent paradox between the antifungal activity of the immunosuppressive agents and the occurrence of fungal infections during their administration, the antifungal attributes of these drugs may influence the spectrum and clinical characteristics of these infections after organ transplantation. Finally, the potent synergistic interactions between the immunosuppressive agents and antifungal drugs against many pathogenic fungi, including those that are typically resistant to traditional antifungal agents, could potentially have a role in devising novel therapeutic strategies for opportunistic mycoses in transplant recipients.

Antifungal Agents↗

Deep mycoses prevalent in the Igbos of Nigeria.

During a 3-year period, 6 cases of Africal histoplasmosis, 6 of phycomycosis and 5 of mycetoma were recognized histologically in 0.4 per cent of 4,307 surgical specimens removed from Nigerian Igbos and examined at a central laboratory. Undoubtedly, these cases are but the representatives of the mycological iceberg existing in this part of the world. Our experience suggests that collaboration between physicians, pathologists and mycologists should bring about increased international awareness of the deep mycoses.

Adult↗

Treatment of superficial and deep-seated mycoses with oral ketoconazole.

Oral ketoconazole was given to 50 patients, 36 with superficial and 14 with deep-seated mycoses. Satisfactory results were obtained in dermatophytoses, pityriasis versicolor, and chronic mucocutaneous candidiasis. Paracoccidioidomycosis also responded well to ketoconazole therapy. The authors' experience in patients with histoplasmosis and aspergillosis does not make it possible to express a firm view on the efficacy of the drug. Ketoconazole is not the recommended drug for treatment of sporotrichosis.

Administration, Oral↗

Fluconazole in the therapy of tropical deep mycoses.

A clinical study was conducted to test the efficacy of fluconazole in the treatment of tropical deep mycoses. Two out of four patients with zygomycosis due to Conidiobolus coronatus who were treated with the drug were completely cured; the other two patients exhibited considerable improvement but could not be followed up. Two patients with eumycetoma, one due to an Acremonium sp. and one due to Pseudallescheria boydii, were treated successfully, whereas another patient with a eumycetoma caused by an unidentified fungus could not be followed up. A complete cure was achieved with one patient with African histoplasmosis and one with candiduria. A case of cerebral phaeohyphomycosis due to Cladosporium sp. showed some improvement but the patient later developed meningitis and died.

Adolescent↗

Paranasal sinus mycoses in north India.

Recognizing the high incidence of paranasal sinus mycoses in north India, we analysed retrospectively the clinical, mycological and management aspects of 178 patients with proven disease attending our institute. On the basis of clinical, radiological, histopathological and mycological findings, the patients could be categorized into those with allergic (8), non-invasive (92) and invasive (78) disease types. Bony erosion without mucosal invasion by fungi was seen in 16 patients with non-invasive disease. Young men from rural areas were the most commonly affected. Rhinorrhoea with nasal polyposis (45.8%) and proptosis (46.4%) was the most common presentation. Concurrent involvement of the maxillary and ethmoid sinuses was common in these patients, whereas isolated sphenoid and frontal sinuses were involved in the invasive variety only. Orbital and intracranial extensions were detected in 100% and 13.2%, respectively, of patients with the invasive type of disease. Aspergillus flavus (79.7%) was the most common isolate. Surgical debridement and sinus ventilation were adequate for the effective management of the non-invasive disease. However, adjuvant medical therapy was included in treatment of the semi-invasive and invasive varieties of the disease. Itraconazole was found to be most useful in prevention of recurrence in the invasive type. Mortality was highest (33.3%) among patients with zygomycotic infection. Invasive fungal granuloma with orbital and intra-cranial invasion is a distinct entity in terms of its clinical course and treatment compared with non-invasive fungal sinusitis, and it needs to be treated aggressively with surgical excision and postoperative itraconazole.

Adolescent↗

[Blood coagulation in domestic deep-seated mycoses].

Activation of blood coagulation to a varying extent affect the course of domestic invasive mycoses. Upon invasion of blood vessels by Candida or aspergilli, occasionally thrombi are formed, which may cause septic embolism. In the course of mucormycosis (syn. zygomycosis) thrombotic occlusion of afflicted blood vessels and subsequent necrosis of dependent tissue regularly occurs. Coagulation during candidosis or aspergillosis may be triggered by secreted aspartic proteinases which are able to activate factor X as has been shown previously [1, 2]. During mucormycosis, severe blood coagulation apparently is due to paracoagulation of fibrinogen which is triggered by low concentrations of extracellular fungal subtilisin-like proteinase (Arp). The enzyme is also able to inactivate the major inhibitor of blood coagulation (antithrombin III). Recent findings on the action of Arp are discussed.

Blood Coagulation↗

Superficial mycoses in Saudi Arabia.

Between June 1988 and December 1990, 1018 cases of superficial mycoses were investigated. Diagnosis was confirmed by microscopic examination in 503 cases and the causal agent was isolated in 490 cases. Tinea capitis accounted for 47.7% (92.5% in children below 10 years of age). The frequency of other clinical types in descending order was pityriasis versicolor 25.8%, tinea corporis 9%, onychomycosis 5.8%, tinea pedis 4%, intertrigo 3.9% and tinea cruris 2.8%. Erythrasma was encountered three times and mixed piedra and trichomycosis axillaris once. Microsporum canis was the commonest aetiological agent, responsible for 46.9% of ringworm infections. Malassezia furfur was the next most common agent (26.5%) followed by Candida albicans (8.6%) and Trichophyton violaceum (8.2%). Other species were found less frequently. T.simii was isolated from four cases of tinea cruris and one each of tinea capitis and tinea corporis, and Piedraia hortae and Trichosporon beigelii from a case of mixed piedra infection.

Adolescent↗

Enzyme immunohistochemistry with mono- and polyclonal antibodies in the pathological diagnosis of systemic bovine mycoses.

To improve the immunohistopathological diagnosis of systemic bovine mycoses, we have evaluated the utility of antifungal polyclonal and monoclonal antibodies, and peroxidase and alkaline phosphatase staining techniques. A rabbit polyclonal antibody to mannan from Candida albicans was specific for candidosis. The diagnosis of aspergillosis was accomplished using a rat monoclonal antibody to the galactofuran side chains of Aspergillus galactomannan. A murine monoclonal antibody reacting with weakly Con-A binding 41 and 46 kDa somatic antigens from Absidia corymbifera was used for immunostaining of zygomycetic hyphae. Peroxidase antiperoxidase (PAP) and alkaline phosphatase antialkaline phosphatase (APAAP) complexes were visualized using aminoethylcarbazole and fast red substrates. A green staining of PAP reactions with dioctyl sulfosuccinate sodium and 3,3',5,5'-tetramethylbenzidine (DONS/TMB) was effective for the demonstration of fungi in dual and triple infections. Tissue sections of experimentally infected mice were used to determine the sensitivity and specificity of the antibodies. Tissues obtained from 161 bovine mycotic lesions previously studied by indirect immunofluorescence staining were further evaluated using the three antibodies. In all of 45 lesions solely affected by aspergillosis and in three solely affected by candidosis the diagnoses were confirmed by the new evaluation. In 85 of 96 cases of single infections with zygomycetes the diagnosis was confirmed, while none of the antibodies reacted with fungal elements in the remaining 11 lesions. Aspergillus hyphae were detected in all three lesions with dual aspergillosis and zygomycosis, whereas zygomycetic material was confirmed in only two of these cases. A mixed infection of candidosis and zygomycosis in a lymph node was confirmed too. In 13 cases in which a diagnosis had not hitherto been obtained, aspergillosis and zygomycosis were recorded each in three cases.

Animals↗

Diagnosis of systemic mycoses by specific immunohistochemical tests.

Immunohistochemistry has proved to be a powerful tool for the accurate diagnosis of a number of important mycoses in humans and animals, such as aspergillosis, candidosis, cryptococcosis, blastomycosis, coccidioidomycosis, histoplasmosis capsulati and duboisii, paracoccidioidomycosis, fusariosis, pseudallescheriosis (scedosporiosis), sporotrichosis, trichosporonosis, penicilliosis, and zygomycosis (mucormycosis). These techniques are also applicable to pneumocystosis and to non-mycotic infections caused by algae such as protothecosis. Apart from the specificity of immunohistochemistry, the application of fluorochromes is highly effective for the localization of typical or atypical fungal elements in lesions with only few organisms present. Occasionally, a dual aetiology of fungal infections may be suspected on the basis of morphological study, and dual staining techniques have the capacity for resolving this question by simultaneous and differential staining of two fungal species present in a tissue specimen.

Animals↗

Activity of MS-8209, a nonester amphotericin B derivative, in treatment of experimental systemic mycoses.

The in vitro and in vivo toxicities and activities of MS-8209, a new hydrosoluble amphotericin B (deoxycholate-amphotericin B [D-AmB]; Fungizone) derivative, were studied. In vitro, MS-8209 was less toxic than AmB against renal tubular cells in primary culture and less active against Candida albicans and Cryptococcus neoformans. However, at 10-fold the AmB concentration, MS-8209 in vitro antifungal activity paralleled that of AmB. Fifty-percent lethal doses of MS-8209 and D-AmB in OF1 noninfected mice were 26 and 2.3 mg/kg, respectively. Therapeutic efficacy of MS-8209 was assessed in murine candidiasis, cryptococcosis, and aspergillosis. In each model of infection, we determined the maximum tolerated dosages of MS-8209 and D-AmB, i.e., the dosage inducing less than 15% mortality due to toxicity; the efficacies of MS-8209 and D-AmB at their respective maximum tolerated dosages were compared. In candidiasis, MS-8209 (15 mg/kg) significantly increased the survival time compared with D-AmB (0.5 mg/kg). Both compounds were equally effective at reducing CFU counts in the kidney. MS-8209 was the most effective agent for increasing the survival time in cryptococcal meningoencephalitis and for reducing CFU counts in spleen, brain, and lung during both cryptococcal pneumonia and meningoencephalitis. In aspergillosis, MS-8209 and D-AmB similarly prolonged the survival of treated mice compared with controls. These results show that when MS-8209 and D-AmB were used at the maximum tolerated dosage, MS-8209 was as effective as or more effective than D-AmB for the treatment of systemic mycoses. These findings warrant further experiments to study the pharmacokinetic properties and toxicity of MS-8209 under conditions of chronic administration.

Amphotericin B↗

Mycoses imported from the West Indies. A report of three cases.

There have been isolated case reports of deep fungal infections from the Caribbean area but little is known about the distribution of mycoses there. Three cases, one of mycetoma, one of chromomycosis, one of histoplasmosis, are described. Their management and the advantages and disadvantages of treatment outside the area of origin are discussed.

Adult↗

Mammary mycoses.

Since 1969 we have had at our hospital a special consulting room for mammary gland diseases in which we have so far seen more than 17,000 patients. Mycoses are a rare disease of the mammary glands. We are reporting below on the incidence of this disease, the mode of infection and the diagnostic possibilities within the framework of our special clinic.

Adult↗

In vitro antifungal spectrum of itraconazole and treatment of systemic mycoses with old and new antimycotic agents.

Itraconazole is a lipophilic triazole with potent in vitro activity. It is also effective after topical, oral and parenteral administration. The antifungal activity of itraconazole has been evaluated against more than 6,500 different strains, belonging to more than 260 fungal species, using the serial decimal dilution test in fluid broth medium (brain-heart infusion broth). Candida spp., Torulopsis spp., Cryptococcus neoformans, Pityrosporum spp. (Dixon broth), various other yeasts, dermatophytes, Aspergillus spp., Penicillium spp., Sporothrix schenckii, dimorphic fungi (mycelium phase and yeast phase), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive. Most strains of Fusarium and Zygomycetes are poorly sensitive. Itraconazole was administered orally and parenterally in normal and immunocompromised guinea-pigs infected with C. albicans, Cr. neoformans, Histoplasma duboisii, S. schenckii, P. marneffei and A. fumigatus. It was effective in terms of both survival of the animals and elimination of the fungi from the various tissues. Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, and to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis. No comparative studies have yet been undertaken for other deep mycoses. The results of combination therapy with itraconazole and fluconazole in cryptococcosis were indifferent; with flucytosine or amphotericin B, additive or synergistic effects were seen in systemic candidosis, cryptococcosis and aspergillosis. No drug-related side-effects were observed after oral or parenteral administration of itraconazole.

Amphotericin B↗

Pathological studies on systemic mycoses in calves.

Systemic mycoses were found in 19 (4.7%) of 406 calves less than 6 months old which were autopsied during the past 10 years. Alimentary mycosis occurred in 12 (63.2%) of 19 cases. In alimentary mycosis, mucormycosis showed the highest rate of occurrence (91.7%, 11/12 calves) followed by aspergillosis 41.7% and candidiasis was 9.3%. Mucormycosis and aspergillosis were characterized by focal hemorrhagic necroses with hyphal proliferation and thrombi in the mucosa and muscular layers of the forestomach, abomasum, and small intestine. Candidiasis was characterized by hyperkeratosis with pseudohyphae and microconidia in the mucosa of the omasum. Four of 12 calves (33.3%) had mixed infections of the alimentary tract consisting of Mucorales and Aspergillus species. Pulmonary aspergillosis was found in 10 (52.6%) of 19 calves. There were micro-abscesses with hyphal proliferation or asteroid bodies in the lungs. Infections involving both the alimentary tract and respiratory organs were noted in 3 (10.5%) of 19 calves. Disseminated mycosis was found only in one calf. In alimentary mycosis, administration of antibiotics for the treatment of diarrhea and early weaning were thought to be an important predisposing factor.

Animals↗

[New developments in therapy of deep mycoses].

Over the past two decades the incidence of deep mycoses caused by several major groups of fungal pathogens such as Candida spp., aspergilli, Cryptococcus neoformans and zygomycetes has risen steadily. Moreover, opportunistic fungal infections due to Fusarium spp., Trichosporon spp., Pseudallescheria boydii and other emerging pathogens, as well as fluconazole-resistant Candida albicans, all of which are often resistant to existing antifungal drugs, are also encountered more and more frequently. This makes it more difficult for the clinician to achieve successful treatment. Thus there is an urgent need to develop new antifungal agents or formulations with advantages over and/or complimentary to existing drugs. This review focuses on current approaches to antifungal chemotherapy with special reference to the clinical development of new drugs, including (ii) lipid formulations of amphotericin B, (i) second-generation azoles and (iii) antifungal lipopeptides.

Amphotericin B↗

[Mycoses and their treatment in malignant hemopathies].

In the last 50 years, the incidence of invasive fungal infections in patients with hematologic malignancies, particularly acute leukemias, has increased from 3 to 30%. Changing epidemiology and the limited advances in the non invasive diagnostic tools contributed to increase the difficulties in the clinical and therapeutic approach. Not only the incidence of invasive mycoses has increased, but they are frequently occurring also in the early phases of the hematologic disease and new fungal pathogens are emerging. In the last years, important progresses have been obtained in the treatment of invasive fungal infections thanks to the use of new antifungal agents and to the new employ of old antifungal drugs. However, considering that the prognosis of these severe complications is related to the early antifungal treatment, the improvement of the diagnostic procedures seems to importantly contribute to the therapeutic progresses.

Antifungal Agents↗

[Variation in mycoses frequency in Mexico].

We show the records about diagnosed mycoses in a hospital in Mexico City in two periods of time: from 1967 to 1977 and from 1993 to 1997. In the former 15,429 patients were studied and in the latter, 5,998. Striking differences among frequency, etiological agents and clinical outcome, were observed. The most frequent infections in both lapses were the superficial ones, however the most recent scores showed a notorious increase in opportunistic infections. We diagnosed only one histoplasmosis case during the period from 1993 to 1997. Etiological agents have also changed, dermatophytes frequency like Trichophyton mentagrophytes and T. tonsurans have diminished while T. rubrum increased from 60% to 80% of the whole dermatophytoses cases. Even though Criptococcus neoformans used to be the only agent causing criptococosis, in the most recent report we found that C. laurentii, C. terreus and C. unigutulatus were also isolated. Another important difference was mortality in rhinocerebral mucormicosis: twenty years ago it was fairly 80%, nowadays it has decreased to 20%.

Cryptococcus↗