PubMed Health⌕ Search

Biomedical subjects

W A Schell

Publications and source records attributed to W A Schell.

At least 19 recordsLinked to original sources
PubMed2004

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Aged, 80 and over↗
PubMed2004

In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans.

The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in vivo in a rabbit model of cryptococcal meningitis. Albaconazole was 100-fold more potent in vitro than fluconazole on a per-weight basis and was fungicidal at potentially relevant concentrations for two isolates. MICs ranged from </=0.0012 to 1.25 micro g/ml, with the MICs for most isolates being between 0.039 and 0.156 micro g/ml. Isolates were from human immunodeficiency virus (HIV)-infected and non-HIV-infected patients and were of serotypes A, B, and C; and the fluconazole MICs for some of the isolates were elevated. Infected rabbits were treated with either fluconazole or albaconazole at dosages ranging from 5 to 80 mg/kg of body weight/day. The peak concentrations of albaconazole in serum and cerebrospinal fluid (CSF) averaged 4.14 and 0.62 micro g/ml, respectively, in animals receiving 80 mg/kg/day. Comparison of the concentrations in serum and CSF suggested a level of CSF penetration of approximately 15%. Despite limited penetration into the subarachnoid space, at all three doses tested albaconazole was as effective as fluconazole for the treatment of cryptococcal meningitis in rabbits.

Animals↗
PubMed2001

Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents.

Dicationic 2,5-bis(4-guanidinophenyl)furans 5a-5f, 2,5-bis[4-(arylimino)aminophenyl]furans 6a-6b and 6e-6k, and 2,5-bis[4-(alkylimino)aminophenyl]furans 6c-6d have been synthesized starting from 2,5-bis[tri-n-butylstannyl]furan. Thermal melting studies with poly dA*dT and the duplex oligomer d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for a number of the compounds. The binding affinities are highly dependent on structure and are significantly affected by substituents both on the phenyl rings of the 2,5-diphenylfuran nucleus and on the cationic centers. Of the 17 novel dicationic compounds synthesized, six (6a, 6b, 5b, 6f, 6h, 6i) exhibited MICs of 2 microg/mL or less versus Mycobacterium tuberculosis. Of the compounds screened against Candida albicans, three gave MICs of 2 microg/mL or less (5b, 6h, 6i), and two (5b, 6i) were fungicidal, unlike a standard antifungal drug fluconazole, which was fungistatic. In addition, one of the tested compounds (6i) exhibited a MIC of <1 microg/mL against Aspergillus fumigatus, while also being a fungicidal against this organism. Finally, when evaluated against an expanded fungal panel, compound 6h showed good activity against Cryptococcus neoformans and Rhizopus arrhizus.

Amidines↗
PubMed2000

Histopathology of fungal rhinosinusitis.

Treatments for the various kinds of fungal rhinosinusitis are fundamentally different, and it is essential to obtain an accurate diagnosis of the particular syndrome in a given case. Microscopic examination of specimens is the most definite and rapid means of establishing a diagnosis of fungal rhinosinusitis. This article compares the utility of various staining and microscopy methods, presents two keys for the algorithmic evaluation of fungal cells as seen in clinical specimens, discusses practical aspects of fungal spore formation within clinical specimens, and reevaluates the role of Candida albicans in rhinosinus disease.

Algorithms↗
PubMed2000

Unusual fungal pathogens in fungal rhinosinusitis.

Approximately 300 fungal species are known to cause mycotic disease in humans and other animals. More than 50 of these species are documented as agents of rhinosinusitis. Most such infections are caused by species of Aspergillus, Rhizopus, Alternaria, Bipolaris, and Curvularia. A growing number, however, has been attributed to lesser known fungi. Here, 38 fungi that are unusual causes of rhinosinusitis are tabulated and referenced in conjunction with their associated symptoms.

Fungi↗
PubMed1998

Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology.

Nontraditional human pathogenic fungi, including Fusarium, Paecilomyces, and Acremonium species, have been increasingly documented as agents of infection in immunocompromised patients and, occasionally, in normal hosts. Although definitive identification of these fungi requires culture, they often can be identified provisionally in tissue sections by a combination of histologic features, including hyaline septate hyphae and characteristic reproductive structures known as phialides and phialoconidia. These morphologic characteristics, although familiar to mycologists, are easily overlooked by histopathologists; as a result, Fusarium species and Paecilomyces lilacinus are frequently misidentified in tissue sections as Aspergillus or Candida species. We identified 19 culture-proved cases of infection with species of Fusarium, Paecilomyces, or Acremonium; retrospectively reviewed histologic specimens stained by routine hematoxylin and eosin, Gomori methenamine silver, and/or periodic acid-Schiff stains; and delineated morphologic criteria that will help pathologists make a preliminary identification of these fungi by histopathology. Adventitious sporulation was found in 9 of 9 infections caused by Paecilomyces species, 7 of 10 infections caused by Fusarium species, and in the single case of infection caused by Acremonium strictum. Histologic recognition of these morphologies may help clinicians select appropriate initial antifungal treatment and manage the infection.

Acremonium↗
PubMed1998

Structure-in vitro activity relationships of pentamidine analogues and dication-substituted bis-benzimidazoles as new antifungal agents.

Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against C. albicans had an MIC80 of </=0.09 microg/ml, and the most potent compound against C. neoformans had an MIC80 of 0.19 microg/ml. Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential.

Antifungal Agents↗
PubMed1998

In vitro antifungal activities of a series of dication-substituted carbazoles, furans, and benzimidazoles.

Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 microg/ml, and it was the most potent compound against C. neoformans (MIC, </=0.09 microg/ml). Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

Antifungal Agents↗
PubMed1998

In vitro and in vivo efficacy of the triazole TAK-187 against Cryptococcus neoformans.

Multiple isolates of Cryptococcus neoformans, including those with fluconazole resistance, were tested to assess the in vitro activity of the new triazole TAK-187. MICs of TAK-187 were at least eightfold lower than those of fluconazole, and fungicidal concentrations for most isolates were 4 microg/ml or less. TAK-187 also was evaluated as intermittent therapy using two dosages in a rabbit model of experimental cryptococcal meningitis. Compared to daily treatment with fluconazole, as little as two doses of TAK-187 given 7 days apart were found to be effective. Plasma and cerebrospinal fluid TAK-187 concentrations were many times higher than MICs and fungicidal concentrations. Based upon its therapeutic efficacy and long half-life in the rabbit model, TAK-187 should be investigated for intermittent dosing in treatment or suppression of cryptococcal infections in humans.

Animals↗
PubMed1997

In vitro antifungal activity of pneumocandin L-743,872 against a variety of clinically important molds.

The in vitro activity of the new antifungal drug pneumocandin L-743,872 against 55 isolates of clinically important molds was examined by an adapted macrobroth dilution method for yeasts. Pneumocandin L-743,872 exhibited in vitro antifungal activity against Alternaria sp., Aspergillus flavus, Aspergillus fumigatus, Curvularia lunata, Exophiala jeanselmei, Fonsecaea pedrosoi, Paecilomyces variotii, and Scedosporium apiospermum. The drug appeared to lack significant in vitro inhibitory activity against Fusarium oxysporum, Fusarium solani, Rhizopus arrhizus, Paecilomyces lilacinus, and Scedosporium prolificans.

Anti-Bacterial Agents↗
PubMed1996

The new fungal opportunists are coming.

Frequent and prolonged exposure of immunocompromised patients to a variety of environmental conditions has resulted in the recognition of infections with new fungal opportunists. Infections with fungi such as Fusarium species, Paecilomyces lilacinus, Acremonium species, Trichosporon beigelii, Blastoschizomyces capitatus, Malassezia furfur, Penicillium marneffei, Scedosporium prolificans, and other dematiaceous species have become significant problems in the treatment of immunocompromised hosts. This discussion addresses several issues of pathogenesis, epidemiology, diagnosis, and treatment with regard to these new opportunists, through a review of both general and specific concepts. The growing need for training in clinical mycology is also summarized.

AIDS-Related Opportunistic Infections↗
PubMed1996

Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy.

OBJECTIVE: To examine the impact of continuous versus intermittent fluconazole therapy on fungal colonization and fluconazole resistance in the oropharynx of HIV-infected patients. DESIGN: Case-control study. SETTING: Duke University Adult Infectious Diseases Clinic, a tertiary referral center in North Carolina which provides care for 700 HIV-infected persons. PATIENTS: Nineteen HIV-infected patients on daily continuous fluconazole for a minimum of 6 months and eleven HIV-infected patients on intermittent fluconazole for a minimum of 6 months were matched by sex and CD4 cell count to HIV-infected patients who had not received fluconazole in the preceding 6 months. MAIN OUTCOME MEASURES: Fungal isolation and fluconazole susceptibility testing were performed on oral saline rinses from each patient. RESULTS: The patients taking continuous fluconazole were more likely than matched controls to have had sterile mouth rinses (14 out of 19 versus five out of 19; P < 0.001), and the yeasts that were isolated were more likely than matched controls to be non-Candida albicans species and to have minimum inhibitory concentrations (MIC) to fluconazole > or = 16 micrograms/ml. None of these isolates were associated with symptoms. In contrast, none of the patients in the intermittent fluconazole group had sterile cultures. When this group was compared to controls, they were more likely to have had non-C. albicans species, and the C. albicans isolates obtained had higher MIC to fluconazole. CONCLUSIONS: Long-term continuous therapy with fluconazole may prevent the appearance of Candida in the oral cavity. This finding may reduce recurrence rates and might favorably impact on the clinical appearance of mucosal candidiasis with resistant C. albicans.

Adult↗
PubMed1996

In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.

Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug were determined, and minimum fungicidal concentrations of SCH56592 and amphotericin B were measured. MICs of SCH56592 were lower than those of amphotericin B and fluconazole but not those of itraconazole. Minimum fungicidal concentrations of SCH56592 were lower than those of amphotericin B. SCH56592 in the presence of human serum produces an in vitro fungicidal effect for Cryptococcus neoformans. The data indicate that SCH56592 might exert fungicidal as well as inhibitory properties in vivo. On the basis of these results, SCH56592 was evaluated with a rabbit model of experimental cryptococcal meningitis; SCH56592 treatment was compared with treatment with fluconazole. Despite no detectable drug concentrations in the cerebrospinal fluid, the activity of SCH56592 against C. neoformans infection was equivalent to that of fluconazole. SCH56592 has potent in vitro activity against C. neoformans and compares favorably to treatment with fluconazole for a central nervous system infection. SCH56592 should be studied for use in humans with cryptococcal infections.

Amphotericin B↗
PubMed1996

Fatal, disseminated Acremonium strictum infection in a neutropenic host.

Disseminated Acremonium strictum infection in a neutropenic patient is reported. Positive fecal cultures preceded positive cutaneous and blood cultures by 18 and 21 days, respectively, which suggests gastrointestinal colonization and invasion as initiating events. Microscopic examination of cutaneous biopsy and pulmonary specimens revealed hyphae, phialides, and phialoconidia in vivo. These adventitious forms also can occur in infections due to other phialidic fungi such as Fusarium and Paecilomyces species and can be misdiagnosed as Candida species. Budding cells also can occur in vivo for species of Fusarium, Paecilomyces, and apparently Acremonium, further adding to the potential for misdiagnosis. The occurrence of adventitious forms in infections caused by species of Acremonium, Fusarium, Paecilomyces, Scedosporium, and Blastoschizomyces is suggested as a mechanism for dissemination of infection and as an explanation of the relatively higher frequency of positive blood cultures in these cases.

Acremonium↗
PubMed1995

Cutaneous infection caused by Curvularia pallescens: a case report and review of the spectrum of disease.

A 75-year-old woman being treated with prednisone and methotrexate had a 5.5 x 2.2 cm ulcer on the leg. A biopsy specimen revealed suppurative, granulomatous dermal inflammation with necrotic areas of septate, branching hyphae containing brown pigment. Cultures grew Curvularia pallescens. Oral ketoconazole therapy was started and the lesion was excised. The site healed after multiple excisions and grafts, and ketoconazole therapy was stopped after 7 months. This is the first reported case of invasive cutaneous infection by C. pallescens.

Aged↗
PubMed1995

New aspects of emerging fungal pathogens. A multifaceted challenge.

This article describes adventitious morphologic forms for species of Fusarium, Paecilomyces, Acremonium, and Scedosporium that can be easily mistaken on histologic, cytologic, and microbiologic examination for Candida species. These forms appear to be correlated with, and may provide explanation for, positive blood cultures in disseminated infections with these species. Adventitious histologic forms also are illustrated for Blastoschizomyces capitatus. Data from culture-proven mycoses for a 15-month period at one medical center are reviewed, and species are listed for which an increase is anticipated. These and other aspects of emerging fungal pathogens are related to the need for strengthened support of mycology training and for federal funding of a mycoses reporting program.

AIDS-Related Opportunistic Infections↗