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Biomedical subjects

M G Rinaldi

Publications and source records attributed to M G Rinaldi.

At least 199 records · Page 11Linked to original sources
PubMed1991

Treatment of murine cryptococcal meningitis with an SCH 39304-amphotericin B combination.

Cryptococcal meningitis was induced in BALB/c mice by intracerebral infection with Cryptococcus neoformans. Drug therapy was initiated 1 day later, with mice receiving amphotericin B (AMB), SCH 39304, combination therapy, or no drug therapy (controls). Most, but not all, combinations showed additive benefits, significantly prolonging survival and reducing organism counts in tissues compared with those in controls and groups which received the drugs independently. Optimum protection was obtained when a single dose of 10 mg of AMB per kg of body weight was combined with a fairly narrow SCH 39304 dose range. AMB antagonism did not occur with any regimen tested. AMB-azole combinations may be reasonable alternatives for patients who fail standard cryptococcosis therapeutic regimens.

Amphotericin B↗
PubMed1991

Demonstration of a cell wall antigen cross-reacting with cryptococcal polysaccharide in experimental disseminated trichosporonosis.

Patients with disseminated infections caused by Trichosporon beigelii have a circulating antigen that cross-reacts with the polysaccharide capsule of Cryptococcus neoformans. We studied the localization of this antigen by immunoelectron microscopy in a rabbit model of experimental disseminated trichosporonosis. Deparaffinized lung sections were examined by using a murine monoclonal anti-cryptococcal polysaccharide antibody and colloidal gold particles coated with goat antibody to murine immunoglobulin G. Antigen that cross-reacted with the monoclonal antibody was observed in the T. beigelii cell wall and in a fibrillar matrix extending from the cell wall.

Animals↗
PubMed1991

Normally saprobic cryptococci isolated from Cryptococcus neoformans infections.

We report two cases in which Cryptococcus laurentii was isolated from surgically resected pulmonary lesions but the cryptococcal cells is tissue reacted positively with a specific fluorescent antibody (FA) conjugate for Cryptococcus neoformans. Both patients had no apparent host defense defects. In both cases, multiple cryptococcal isolates were obtained from tissue, and yeastlike cells consistent with C. neoformans were seen in direct histology. The isolates were identified by assimilation patterns and standard procedures including phenoloxidase reactions. Since C. laurentii was consistently isolated by using stringent procedures, it was considered unlikely that the fungus represented surgical or laboratory contamination. Its presence may be the result of dual infection not detected by FA, but other possible explanations exist. The results show the value of the FA test in diagnostic mycology and call into question previous reports of cryptococci other than C. neoformans as agents of infection.

Adult↗
PubMed1990

Cutaneous phaeohyphomycosis caused by a rare fungal pathogen, Hormonema dematioides: successful treatment with ketoconazole.

Annular, fungating, ulcerated lesions developed on both hands of a 64-year-old immunocompetent man 2 months after he was cut with barbed wire. A dematiaceous mold, Hormonema dematioides, heretofore not definitively associated with human disease, was grown from two separate tissue specimens during a period of 9 days. Histopathologic examination demonstrated rare small, periodic acid-Schiff-positive, hyaline, yeastlike organisms in tissue. Twelve weeks of empiric therapy with ketoconazole, 400 mg/day, was curative.

Dermatomycoses↗
PubMed1990

Itraconazole treatment of phaeohyphomycosis.

Nineteen patients with phaeohyphomycosis were treated with itraconazole. Of these, 17 were assessable for clinical outcome. Of these, two had received no prior therapy, five had failed amphotericin B therapy, four had failed ketoconazole or miconazole therapy, and five had failed both amphotericin B and azole therapy. One patient had received only prior surgical intervention. Fungi of seven different genera caused disease of the skin in nine patients, soft tissue in nine, sinuses in eight, bone in five, joints in two, and lungs in two. Itraconazole was given in dosages ranging from 50 to 600 mg/day for 1 to 48 months. Clinical improvement or remission occurred in nine patients. Two patients have had stabilization of disease. Six patients failed treatment, one had a relapse after initially successful treatment. Itraconazole appears to be highly effective in some patients with phaeohyphomycosis, including patients refractory to other antifungal agents.

Adult↗
PubMed1990

Itraconazole therapy for nonmeningeal coccidioidomycosis: clinical and laboratory observations.

Itraconazole, a new oral triazole antifungal agent, was administered in 75 courses to patients with chronic coccidioidomycosis at dosages of 50 to 400 mg/day for a median duration of 10 months. Assessment of efficacy was made with a standardized scoring system. Responses were seen in 42 of 58 assessable courses (72%). Nonresponse occurred exclusively in patients who had failed previous therapy and was most common in pulmonary disease. Toxicity was minimal at the doses studied. Pharmacokinetic analysis of itraconazole in serum at steady state showed negligible circadian variation; differences in serum concentrations among patients were large. Clinical isolates of Coccidioides immitis showed uniform in vitro susceptibility to itraconazole. Itraconazole shows impressive activity in this series of patients with refractory coccidioidomycosis. Further evaluation of itraconazole in this and in other systemic mycoses is in order.

Adolescent↗
PubMed1990

Endocarditis and hip arthritis associated with Scedosporium inflatum.

A 30-year-old man had endocarditis and hip arthritis associated with the recently recognized fungus, Scedosporium inflatum. Inhibition, and possibly cure, of endocarditis occurred with medical therapy alone. Data from in vitro susceptibility testing did not predict clinical response. This case also illustrates the need to standardize fungal susceptibility testing and to remain vigilant for emerging pathogens.

Adult↗
PubMed1990

In vitro and in vivo activities of Sch 39304, fluconazole, and amphotericin B against Histoplasma capsulatum.

The antifungal activities of amphotericin B and two triazoles, Sch 39304 and fluconazole, were tested against Histoplasma capsulatum. In this study Sch 39304 compared favorably with amphotericin B in treating histoplasmosis in normal and leukopenic mice, whereas fluconazole was much less active. The differences in the efficacies of the triazoles appeared to be due to differences in their pharmacokinetics and the dosage schedule that was used. For amphotericin B there was a good correlation between in vitro and in vivo efficacy, but this was not true of the triazole derivatives. These results further demonstrate that, with the methods used in this study, in vitro susceptibility testing of triazoles may not be predictive of in vivo activity against isolates of H. capsulatum.

Amphotericin B↗
PubMed1990

Penetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates.

We characterized the cerebrospinal fluid (CSF) penetration and pharmacokinetics of SCH-39304 in adult rhesus monkeys receiving a single oral dose of SCH-39304 (2.0 mg/kg of body weight). The mean CSF-to-plasma area under the curve ratio was 0.63 (+/- 0.18, standard error of the mean); maximum concentrations were 1.34 micrograms/ml (+/- 0.18) in CSF and 1.96 micrograms/ml (+/- 0.43) in plasma. The mean plasma half-life was 45.7 h (+/- 11), and mean CSF half-life was 38.7 h (+/- 3.5). The mean levels of SCH-39304 at 24 h were 1.48 micrograms/ml (+/- 0.3) in plasma and 0.96 microgram/ml (+/- 0.12) in CSF. We conclude that SCH-39304 effectively penetrates into CSF and achieves concentrations considered active against many opportunistic yeasts and that these concentrations are sustained in CSF for greater than or equal to 24 h.

Animals↗
PubMed1990

Collaborative investigation of variables in susceptibility testing of yeasts.

A multicenter study was performed to evaluate the effect of medium, incubation time (24 and 48 h), and temperature (30 and 35 degrees C) on intra- and interlaboratory variations in MICs of flucytosine, amphotericin B, and ketoconazole for yeasts. Testing was performed on coded isolates of Candida species (11 strains) and Cryptococcus neoformans (2 strains) by using a standard macrodilution protocol 11 laboratories. Four chemically defined media buffered to pH 7.0 with morpholinepropanesulfonic acid were evaluated, including buffered yeast nitrogen base, synthetic amino acid medium-fungal, RPMI 1640 medium, and high-resolution antifungal assay medium. Intralaboratory variability was less than or equal to fourfold for 97% of the replicate sets of data. The highest level of interlaboratory agreement, irrespective of antifungal agent or incubation conditions, was observed with RPMI 1640 medium. Intralaboratory variability was less than or equal to fourfold for 93% of the determinations with ketoconazole and 100% with flucytosine tested in RPMI 1640 medium at 35 degrees C for 24 h. Variability in amphotericin B results was less than or equal to fourfold for 81% of the determinations in RPMI 1640 medium at 35 degrees C for 48 h. The rank order of MICs within each antifungal test group was similar among the various laboratories and was generally in agreement with the reference rank order regardless of the test medium that we used.

Amphotericin B↗
PubMed1990

Patterns of morphologic variation among isolates of Trichosporon beigelii.

We observed considerable variability in colony and microscopic morphology among isolates of Trichosporon beigelii. Deeply invasive clinical isolates showed four distinct morphotypes and spontaneous conversions among certain morphotypes and grew well at 37 degrees C. In contrast, superficial clinical and environmental isolates did not demonstrate such morphotypes or conversions, and most grew poorly at 37 degrees C. Thus, the morphologic and physiologic features of invasive clinical isolates of T. beigelii follow certain patterns distinct from those of superficial clinical and environmental isolates.

Genetic Variation↗
PubMed1990

Trichosporon beigelii, an emerging pathogen resistant to amphotericin B.

Trichosporon beigelii caused fatal disseminated infections that were resistant to amphotericin B in two granulocytopenic patients. In vitro susceptibility studies demonstrated that both index strains of T. beigelii were inhibited but not killed by amphotericin B at achievable concentrations in serum. The minimum lethal concentration for both isolates was greater than or equal to 18 micrograms/ml. Five of seven other isolates were found to have a similar pattern of amphotericin B resistance. The fact that the minimum lethal concentration of T. beigelii was many times greater than its MIC was consistent with a resistance pattern of tolerance. We concluded that T. beigelii may be resistant in vitro to amphotericin B and that this in vitro resistance was correlated with refractory, disseminated trichosporonosis in granulocytopenic patients. T. beigelii should be included in the expanding list of amphotericin B-resistant fungi.

Adolescent↗
PubMed1990

Pulmonary aspergillosis in mice: treatment with a new triazole SCH39304.

The triazole SCH39304 was compared with amphotericin B and fluconazole for the treatment of pulmonary aspergillosis in corticoid-immunosuppressed mice intranasally challenged with 5 x 10(6) conidia of Aspergillus fumigatus. In vitro, the minimum inhibitory concentration (MIC) for fluconazole was greater than 80 micrograms/ml, for SCH39304 40 micrograms/ml, and for amphotericin B 0.29 micrograms/ml. Beginning 1 day after challenge, groups of 10 mice were treated orally, twice daily, for 15 days with Noble agar (control), SCH39304, fluconazole, or amphotericin B at various doses. For lung tissue counts of A. fumigatus, mice were similarly challenged and treated only for 5 days with SCH39304, fluconazole, or amphotericin B. Only SCH39304 significantly reduced the number of A. fumigatus in the lung. SCH39304 at doses of 5 mg/kg or higher significantly prolonged the survival of mice, as did amphotericin B at 3 mg/kg. Fluconazole did not significantly prolong survival at doses of 15 or 30 mg/kg. SCH39304 appears to be as effective as amphotericin B in murine pulmonary aspergillosis and warrants further evaluation for aspergillosis in humans.

Amphotericin B↗
PubMed1989

Emerging fungal pathogens.

Fungi such as Fusarium spp., Curvularia spp., Alternaria spp. or Trichosporon beigelii, had been thought to represent contamination or harmless colonization when isolated from humans. More recently, the role of these and other newly recognized fungi as serious pathogens has been clearly established. Three diverse groups of fungi are responsible for these infections: the agents of phaeohyphomycosis and hyalohyphomycosis and certain yeasts. These infections, which have been encountered in both presumably healthy and immuno-compromised individuals, tend to be localized in the former, and disseminated and frequently fatal in the latter group of patients. A major concern is that these organisms are not uniformly susceptible to amphotericin B. Standardization of antifungal susceptibility testing may, therefore, be helpful in determining the antifungal drug of choice for each infection. It is also hoped that the advent of newer antifungals and biologic response modifiers will have a significant impact on the morbidity and mortality of these emerging infections.

Alternaria↗
PubMed1989

Bipolaris hawaiiensis-caused phaeohyphomycotic orbitopathy. A devastating fungal sinusitis in an apparently immunocompetent host.

The authors present a case report of a devastating bilateral optic neuropathy and orbitopathy initiated by a contiguous fungal sinusitis, in an apparently immunocompetent young man. The causative organism, Bipolaris hawaiiensis, and other species classified in the genus Bipolaris, are being recognized with increased frequency as causes of several ophthalmic and systemic disorders in both immunocompromised and normal hosts. A literature review demonstrates the variety of clinical presentations with emphasis on those cases which may present to the ophthalmologist.

Adult↗
PubMed1989

Phaeohyphomycotic cutaneous disease caused by Pleurophoma in a cardiac transplant patient.

A 56-y-old female cardiac transplant patient treated with cyclosporine and prednisone noted the onset of three nontender red nodules on the legs and arms after gardening. Biopsy of all lesions revealed inflammatory cells and hyphal elements in the dermis. The dematiaceous fungus cultured from biopsy tissue was a pycnidial-forming organism of the genus Pleurophoma. The lesions responded to the topical application of miconazole.

Female↗