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W E Dismukes

Publications and source records attributed to W E Dismukes.

At least 19 recordsLinked to original sources
PubMed1995

Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

There are few clinical data concerning the use of fluconazole, a triazole antifungal agent with in vitro activity against Blastomyces dermatitidis, in the treatment of human blastomycosis. We conducted a multicenter, randomized, open-label pilot trial comparing two daily doses of fluconazole (200 mg and 400 mg) in the treatment of non-life-threatening, non-CNS blastomycosis. Twenty-four patients were enrolled in the study, and 23 patients were evaluable for efficacy analysis. Overall, treatment of 15 (65%) of 23 patients was successful, including eight (62%) of 13 who received 200 mg daily and seven (70%) of 10 who received 400 mg daily. The mean duration of therapy for successfully treated patients was 6.7 months. Of the six patients whose prior antifungal therapy had failed, all six eventually responded to fluconazole treatment. We conclude that fluconazole (200 mg to 400 mg daily) given for at least 6 months is moderately effective treatment for blastomycosis.

Adolescent↗
PubMed1995

Cryptococcal empyema: case report and review.

A 28-year-old male infected with the human immunodeficiency virus (HIV) developed a pleural empyema caused by Cryptococcus neoformans. He responded well to chest-tube drainage and antifungal therapy; he received fluconazole as maintenance therapy for 1 year and has not relapsed. We reviewed the English-language literature on cryptococcal pleural effusions in patients with and without AIDS. Only three other cases of empyema, one of them in an HIV-infected patient, have been reported. A pleural-fluid cryptococcal antigen test was diagnostic in our case and should be included in the diagnostic evaluation of unexplained pleural empyema/effusion in immunocompromised patients.

AIDS-Related Opportunistic Infections↗
PubMed1993

Management of cryptococcosis.

Cryptococcosis is a common opportunistic fungal disease in immunocompromised patients and also may occur in normal hosts. Cryptococcal disease most frequently involves the lungs and central nervous system. Management remains controversial, especially in patients with life-threatening disease and those with underlying T-cell dysfunction due to AIDS, neoplasia, or corticosteroid therapy. While amphotericin B, usually in combination with flucytosine, generally is recommended as primary therapy for patients with severe forms of disease, especially cryptococcal meningitis, alternative treatment regimens have been developed or are under investigation. These include the use of an oral triazole alone (fluconazole or itraconazole), an all-oral combination of fluconazole and flucytosine, and a novel induction-consolidation regimen using several drugs. Patients with AIDS are at high risk of relapse; consequently, chronic maintenance therapy is indicated. For patients with cryptococcal meningitis who have hydrocephalus or other central nervous system complications, aggressive adjunctive measures such as ventricular shunting must be employed.

AIDS-Related Opportunistic Infections↗
PubMed1992

Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group.

OBJECTIVE: To assess the efficacy and toxicity of orally administered itraconazole in the treatment of nonmeningeal, nonlife-threatening forms of blastomycosis and histoplasmosis. DESIGN: Prospective, nonrandomized, open trial. SETTING: Multicenter trial at 14 university referral centers. PATIENTS: Eighty-five patients with culture or histopathologic evidence of blastomycosis (48 patients) or histoplasmosis (37 patients). Patients receiving other systemic antifungal therapy were excluded. INTERVENTIONS: Itraconazole was administered orally at doses of 200 to 400 mg/d. Patients in whom treatment was considered a success were treated for a median duration of 6.2 months (blastomycosis) and 9.0 months (histoplasmosis). Disease activity was assessed at baseline; drug efficacy and toxicity were evaluated at monthly intervals during therapy, and efficacy was evaluated at regular follow-up visits after completion of therapy. The median duration of posttreatment evaluation for successfully treated patients was 11.9 months (blastomycosis) and 12.1 months (histoplasmosis). MEASUREMENTS AND MAIN RESULTS: Among the 48 patients with blastomycosis, success was documented in 43 (90%). The success rate for patients treated for more than 2 months was 95% (38 of 40). Among the 37 patients with histoplasmosis, success was documented in 30 (81%). The success rate for patients treated for more than 2 months was 86% (30 of 35). All patients with histoplasmosis in whom treatment failed had chronic cavitary pulmonary disease. Toxicity was minor; only 25 (29%) patients experienced any side effects, and itraconazole toxicity necessitated stopping therapy in only 1 patient. CONCLUSIONS: Itraconazole is a highly effective therapy for nonmeningeal, nonlife-threatening blastomycosis and histoplasmosis. The drug is associated with minimal toxicity.

Adult↗
PubMed1992

Evaluation of new antifungal drugs for the treatment of systemic fungal infections. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines are applicable to all fungal pathogens that produce systemic infections in humans. Specific examples are provided whenever they might clarify special issues. Systemic fungal infections usually are divided into two broad categories: endemic systemic fungal diseases, which occur classically in healthy hosts, and opportunistic fungal diseases, which occur almost exclusively in patients with impaired host defenses. Both the increasing frequency of disseminated histoplasmosis and coccidioidomycosis in patients with AIDS and the occurrence of candidemia due to vascular-line infections have begun to blur this distinction. The fungi included in these guidelines are Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Candida species, Cryptococcus neoformans, Aspergillus species, and Sporothrix schenckii. Diagnosis of infections caused by these fungi should be based on culture of infected body fluids or tissues whenever possible. Cryptococcal and coccidioidal meningitis are exceptions. Amphotericin B remains the standard comparative agent for most new agents. Further studies of the efficacy of new oral agents used alone or after a hospital course of amphotericin B are needed. The agents currently available are usually inadequate for eradication of fungal infections in patients with AIDS, who may need prolonged treatment. Final assessment for these patients may need to be classified as clinical cure with presumed microbiologic persistence.

Antifungal Agents↗
PubMed1991

In vitro comparison of cilofungin alone and in combination with other antifungal agents against clinical isolates of Candida species.

Cilofungin, a lipopeptide antifungal agent, was tested for in vitro activity alone and in combination with ketoconazole, itraconazole, flucytosine and amphotericin B against 102 clinical isolates of Candida species. At 48 hours all isolates of Candida albicans, Candida tropicalis, Candida paratropicalis and Candida glabrata were inhibited by less than or equal to 5 meg/ml of cilofungin. In contrast, the MIC90 for Candida krusei was 10 mcg/ml and for Candida parapsilosis greater than 40 mcg/ml. The interaction of combinations of cilofungin with amphotericin B, itraconazole, ketoconazole and flucytosine was additive or indifferent at 48 hours for 100%, 88%, 78% and 70% of all Candida species isolates, respectively. Overall, cilofungin demonstrated good activity in vitro against most Candida species isolates.

Amphotericin B↗
PubMed1990

A randomized, double-blind trial of nystatin therapy for the candidiasis hypersensitivity syndrome.

BACKGROUND: Candida albicans infection has been proposed to cause a chronic hypersensitivity syndrome characterized by fatigue, premenstrual tension, gastrointestinal symptoms, and depression. Long-term antifungal therapy has been advocated as treatment for the syndrome, which is most often diagnosed in women with persistent or recurrent candida vaginitis. METHODS: To determine the efficacy of nystatin therapy for presumed candidiasis hypersensitivity syndrome, we conducted a 32-week randomized, double-blind, cross-over study using four different combinations of nystatin or placebo given orally or vaginally in 42 premenopausal women who met present criteria for the syndrome and had a history of candida vaginitis. The outcomes studied were the changes from base line in scores for vaginal, systemic, and overall symptoms and in the results of standardized psychological tests. RESULTS: The three active-treatment regimens (oral and vaginal nystatin, oral nystatin and vaginal placebo, and oral placebo and vaginal nystatin) and the all-placebo regimen significantly reduced both vaginal and systemic symptoms (P less than 0.001), but nystatin did not reduce the systemic symptoms significantly more than placebo. On average, the scores for systemic symptoms improved 25 percent with the three active-treatment regimens and 23 percent with the all-placebo regimen, a difference of only 2 percent (95 percent confidence interval, -3 to 7 percent). As expected, the three active-treatment regimens were more effective than placebo in relieving vaginal symptoms (P less than 0.001). All four regimens reduced psychological symptoms and global indexes of distress; there were no significant differences among the treatment regimens. CONCLUSIONS: In women with presumed candidiasis hypersensitivity syndrome, nystatin does not reduce systemic or psychological symptoms significantly more than placebo. Consequently, the empirical recommendation of long-term nystatin therapy for such women appears to be unwarranted.

Administration, Oral↗
PubMed1990

Itraconazole treatment of coccidioidomycosis. NAIAD Mycoses Study Group.

PURPOSE: The purpose of this study was to assess the tolerance and efficacy of itraconazole in the treatment of coccidioidomycosis. PATIENTS AND METHODS: Fifty-one patients with nonmeningeal coccidioidomycosis were considered for treatment with intraconazole. Forty-nine patients who met study criteria were treated with itraconazole given orally in doses of 100 to 400 mg/day for periods up to 39 months. Of these patients, 12 had osteoarticular disease, 23 had chronic pulmonary disease, and 14 had skin or soft tissue disease. Clinical response was evaluated using a scoring system accounting for lesion number and size, symptoms, culture, and serologic titer. Remission was defined as reduction of the pretreatment score by 50% or more. RESULTS: Patients with osteoarticular, chronic pulmonary, and soft tissue disease improved at similar rates. Because two patients had no scoring assessment for efficacy, they were considered inassessable for efficacy. Forty-seven patients are evaluable. Of these patients, 44 have completed therapy, and three are still receiving itraconazole. Of the 44 patients no longer receiving therapy, 25 (57%) achieved remission. Of the 25 patients achieving remission, four later experienced a relapse. Therapy failed in 19 patients (43%). Of these cases, 16 (36%) were clinical failures and three (7%) developed drug intolerance that precluded continuation of treatment. Evaluation of culture conversions was of limited value in the osteoarticular patients, fewer than half of whom had follow-up biopsies. However, culture conversions were a useful index of response in patients with chronic pulmonary disease. During the course of treatment, serologic titers declined in the two groups with extrapulmonary disease, but not in patients with pulmonary coccidioidomycosis. Possible toxicities were generally mild. CONCLUSION: Itraconazole appears efficacious and very well tolerated in patients with coccidioidomycosis.

Adolescent↗
PubMed1990

Comparison of cilofungin and amphotericin B for therapy of murine candidiasis.

We compared the efficacies of cilofungin and amphotericin B treatment in a murine model of disseminated candidiasis. Three different dosages of each drug plus controls were evaluated. Statistically improved survival was noted only among mice treated with 1 mg of amphotericin B per kg of body weight (P less than 0.05). While all amphotericin B regimens and the two lower-dosage cilofungin regimens significantly reduced yeast cell counts in kidneys compared with the controls, the amphotericin B-treated mice had a significantly higher percentage of sterile kidneys following therapy compared with those treated with cilofungin (P = 0.0001).

Amphotericin B↗
PubMed1988

Ketoconazole therapy of progressive coccidioidomycosis. Comparison of 400- and 800-mg doses and observations at higher doses.

One hundred and twelve patients with progressive pulmonary, skeletal, or soft tissue infections caused by Coccidioides immitis were randomly assigned to treatment with 400 or 800 mg per day dosages of ketoconazole. During therapy, if response was unsatisfactory, the protocol provided for treatment with higher doses. With 400 mg, ketoconazole resulted in 23.2 percent successes, which was similar to 32.1 percent successes with 800-mg treatments (p = 0.29). An additional six of 23 patients in whom initial therapy failed and who later received 1,200 or 1,600 mg per day of ketoconazole also showed improvement. However, among patients completing successful courses of therapy, relapses were more frequent in those requiring higher than 400-mg dosages for their success. From these studies, it is concluded that ketoconazole in doses above those currently recommended offer little or no benefit for most patients with non-meningeal forms of coccidioidomycosis.

Adult↗
PubMed1988

Cryptococcal meningitis in patients with AIDS.

The Cryptococcus has become a major cause of meningitis in patients infected with the human immunodeficiency virus (HIV), and the expression of cryptococcal infection in this population of patients is quite unique. Often the infection is devoid of inflammatory response and is associated with very high antigen and fungal titers. Response to amphotericin therapy is erratic, and relapse is common. We have asked Dr. William E. Dismukes, principal investigator of the NIAID Mycoses Study Group, to discuss the following clinical questions: When and how does cryptococcal infection in HIV-infected patients present? How does it differ in HIV-infected and non-HIV-infected individuals? How is the diagnosis established? What is the sensitivity of the CSF cryptococcal antigen test? Is the serum antigen test of any value? What is the best way to treat patients--the recommended drugs, dosages, and duration of therapy? Is maintenance therapy necessary, and finally, what drugs are available for it? [Please note that an AIDS training program is now available for members of the Infectious Diseases Society of America and that details of this program appear in the Notices section of this Journal issue (pages 859-60).]

Acquired Immunodeficiency Syndrome↗
PubMed1988

Ketoconazole treatment of coccidioidal meningitis.

Fifteen patients with coccidioidal meningitis were treated with high doses of ketoconazole for up to 4 years. Five patients were treated with ketoconazole alone. One clinically failed, one developed hepatotoxicity, and three achieved remission of meningitis. One patient received intrathecal AMB in addition to ketoconazole for only 2 weeks before continuing on ketoconazole alone. He improved, but discontinued ketoconazole because of nausea and vomiting, and suffered a lethal relapse. Nine patients received ketoconazole in combination with prolonged courses of intrathecal AMB. Two patients were failures from nausea and vomiting, and the remaining seven either improved or experienced remission. The clinical responses appeared to be similar in patients receiving high-dose ketoconazole, either alone or combined with AMB, suggesting that there is no clinically significant antagonism of the drugs. Nausea and vomiting are significant limitations of high-dose ketoconazole. Ketoconazole alone is effective in some patients with coccidioidomycotic meningitis.

Amphotericin B↗
PubMed1988

Azole antifungal agents: emphasis on new triazoles.

Many advances have been made in antifungal therapy over the last three decades. Itraconazole and fluconazole, two investigational triazole agents, are the most recent additions to the list of antifungal drugs. This review has focused primarily on their mechanisms of action, favorable pharmacologic properties, and spectra of activity against a broad range of systemic pathogens. Itraconazole and fluconazole show much promise as orally active agents, with less potential for toxicity than the currently available azoles. Fluconazole and, to a lesser degree, itraconazole are especially promising therapies for cryptococcal meningitis. In addition, fluconazole may prove to be highly effective in urinary tract infections caused by Candida species and other fungi. Ongoing and future clinical trials will more clearly define the specific roles of itraconazole and fluconazole in the treatment of systemic mycoses.

Animals↗
PubMed1988

Treatment of histoplasmosis and blastomycosis.

Prior to the development of ketoconazole, the treatment of systemic histoplasmosis and blastomycosis was limited to AMB. The convenience of oral dosing, combined with avoidance of the significant toxicities associated with AMB, make ketoconazole an attractive alternative for the treatment of selected forms of histoplasmosis and blastomycosis. Although high-dose (800 mg/day) ketoconazole is generally more effective than low-dose (400 mg/day), therapy should be initiated at the lower dose due to significantly more adverse effects at higher doses; the daily dose should be increased in patients with progressive disease. Caution should be exercised when ketoconazole is used to treat patients with GU tract disease and in patients with naturally occurring or pharmacologically induced achlorhydria. Thus, AMB remains the drug of choice for difficult to treat cases of histoplasmosis and blastomycosis; however, recent studies have established ketoconazole as the drug of choice in immunocompetent patients with non-life-threatening, non-meningeal H capsulatum and B dermatitidis disease.

Amphotericin B↗