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PubMed1989

[In vivo and in vitro suppression of lymphocyte function in paranasal sinus mycoses].

In about 10% of patients operated on a chronic sinusitis, an aspergilloma is found in the paranasal sinus. To detect possible underlying immunodeficiencies, patients with aspergilloma were subjected to an immunological screening programme. The data were compared with those of patients suffering from non-mycotic chronic sinusitis and healthy controls. Totale lymphocyte counts and immunological levels were normal in both groups of sinusitis. Leukocyte subset analyses by membrane fluorescence revealed a significant decrease of CD11+ cells, i.e. macrophages/monocytes and NK cells, in both types of sinusitis. Furthermore, a markedly enhanced frequency of CD25+-cells, i.e. IL 2-receptor bearing cells, was observed in patients with aspergilloma. Peripheral blood lymphocytes of both groups of patients showed a significant reduction in the proliferative response to both T and B-cell mitogens, the values for the mitogens ConA and PWM being significantly lower in aspergilloma patients than in those with non-mycotic sinusitis. This lack of lymphocyte stimulation in the aspergilloma group was also manifest in skin tests to recall antigens. These first data suggest an immunodeficiency in association with chronic sinusitis caused by Aspergillus fumigatus. Further studies are needed to clarify if this defect is cause or result of the mycotic infection.

Adult↗
PubMed1992

Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group.

BACKGROUND: Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS: In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS: Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS: Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.

Acquired Immunodeficiency Syndrome↗
PubMed1992

A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group.

BACKGROUND: After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS: We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS: Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS: Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.

BACKGROUND: Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization. METHODS: In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks. RESULTS: At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P=0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization. CONCLUSIONS: For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.

AIDS-Related Opportunistic Infections↗
PubMed2000

The usefulness of blood culture in diagnosing HIV-related systemic mycoses: evaluation of a manual lysis centrifugation method.

The results of 5034 blood cultures, implementing a lysis-centrifugation method with saponin, are summarized in this paper. Three hundred and twenty-two blood samples (6.3%) obtained from a pool of human immunodeficiency virus (HIV)-positive patients yielded fungi. Cryptococcus neoformans was isolated in 199 samples (3.95%), Histoplasma capsulatum in 95 (1.89%). Candida parapsilosis in 12 (0.23%), C. albicans in 7 (0.13%), C. tropicalis in 2, C. krusei in 1, C. guillermondii in 1, and Prototheca wickerhamii in 4 (0.07%). Blood cultures were positive for C. neoformans in 76.23% of patients having a diagnosis of cryptococcosis and in 89.65% of those who had histoplasmosis. The blood culture was the first means of confirming the diagnosis in 23.8% of the patients with cryptococcosis and in 54% with histoplasmosis. In the four patients in whom P. wickerhamii was isolated, a diagnosis of disseminated protothecosis was not achieved by other findings. Catheter infections were responsible for the majority of recovered Candida spp.

AIDS-Related Opportunistic Infections↗
PubMed2002

Chrysosporium anamorph of Nannizziopsis vriesii associated with fatal cutaneous mycoses in the salt-water crocodile (Crocodylus porosus).

The Chrysosporium anamorph of Nannizziopsis vriesii, recently identified as the cause of cutaneous infections in chameleons and brown tree snakes, was associated with skin infections and deaths in salt-water crocodile (Crocodylus porosus) hatchlings on two separate occasions 3 years apart. In all, 48 animals died from the infection. All hatchlings came from the same farm in northern Queensland, Australia.

Alligators and Crocodiles↗
PubMed2000

Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents. We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days. In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P<.001), with higher eradication rates among patients completing 14 days of therapy (P<.0001), including 33 (52%) of 64 catheterized and 42 (78%) of 54 noncatheterized patients. Pretreatment serum creatinine levels were inversely related to candiduria eradication. Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients. Oral fluconazole was safe and effective for short-term eradication of candiduria, especially following catheter removal. Long-term eradication rates were disappointing and not associated with clinical benefit.

Aged↗
PubMed2000

Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups.

This study was undertaken to characterize the laboratory and clinical course of patients with AIDS and cryptococcal meningitis who had normal or elevated cerebrospinal fluid (CSF) pressure. Data were obtained retrospectively from a randomized multicenter quasifactorial phase III study comparing amphotericin B with or without flucytosine in primary treatment of cryptococcal meningitis. CSF pressure was measured before treatment and at 2 weeks. Repeated lumbar punctures were done to drain CSF and to reduce pressure. Patients with the highest baseline opening pressures (> or = 250 mm H2O) were distinguished by higher titers of cryptococcal capsular polysaccharide antigen in CSF; more frequently positive India ink smears of CSF; and more frequent headache, meningismus, papilledema, hearing loss, and pathological reflexes. After receiving antifungal therapy, those patients whose CSF pressure was reduced by >10 mm or did not change had more frequent clinical response at 2 weeks than did those whose pressure increased >10 mm (P<.001). Patients with pretreatment opening pressure <250 mm H2O had increased short-term survival compared with those with higher pressure. We recommend that opening pressures >/=250 mm H2O be treated with large-volume CSF drainage.

AIDS-Related Opportunistic Infections↗
PubMed2000

Practice guidelines for the management of patients with sporotrichosis. For the Mycoses Study Group. Infectious Diseases Society of America.

UNLABELLED: The recommendations for the treatment of sporotrichosis were derived primarily from multicenter, nonrandomized treatment trials, small retrospective series, and case reports; no randomized, comparative treatment trials have been reported. Most cases of sporotrichosis are non life-threatening localized infections of the skin and subcutaneous tissues that can be treated with oral antifungal agents. The treatment of choice for fixed cutaneous or lymphocutaneous sporotrichosis is itraconazole for 36 months. The preferred treatment for osteoarticular sporotrichosis also is itraconazole, but therapy must be continued for at least 12 months. Pulmonary sporotrichosis responds poorly to treatment. Severe infection requires treatment with amphotericin B; mild to moderate infection can be treated with itraconazole. Meningeal and disseminated forms of sporotrichosis are rare and usually require treatment with amphotericin B. AIDS patients most often have disseminated infection and require life-long suppressive therapy with itraconazole after initial use of amphotericin B. OVERVIEW: Sporotrichosis is caused by the dimorphic fungus Sporothrix schenckii, which is found throughout the world in decaying vegetation, sphagnum moss, and soil. The usual mode of infection is by cutaneous inoculation of the organism. Pulmonary and disseminated forms of infection, although uncommon, can occur when S. schenckii conidia are inhaled. Infections are most often sporadic and usually associated with trauma during the course of outdoor work. Infection can also be related to zoonotic spread from infected cats or scratches from digging animals, such as armadillos. Outbreaks have been well-described and often are traced back to activities that involved contaminated sphagnum moss, hay, or wood. Most cases of sporotrichosis are localized to the skin and subcutaneous tissues. Dissemination to osteoarticular structures and viscera is uncommon and appears to occur more often in patients who have a history of alcohol abuse or immunosuppression, especially AIDS. Spontaneous resolution of sporotrichosis is rare, and treatment is required for most patients. Although sporotrichosis localized to skin and subcutaneous tissues is readily treated, management of osteoarticular, other localized visceral, and disseminated forms of sporotrichosis is difficult. OBJECTIVE: The objective of these guidelines is to provide recommendations for the treatment of various forms of sporotrichosis. OUTCOMES: The desired outcomes of treatment include eradication of S. schenckii from tissues, resolution of symptoms and signs of active infection, and return of function of involved organs. In persons with AIDS, eradication of the organism may not be possible, but clinical resolution should be attained and subsequently maintained with suppressive antifungal therapy. EVIDENCE: The English-language literature on the treatment of sporotrichosis was reviewed. Although randomized, blinded, controlled treatment trials were sought, none were found to have been performed for the treatment of sporotrichosis. Therefore, most weight was placed on those reports that were derived from multicenter trials of specific treatment modalities for sporotrichosis. Small series from a single institution and individual case reports were accorded less importance. VALUES: The highest value was placed on clinical efficacy and the ability of the antifungal regimen to eradicate the organism, but safety, tolerability, and cost of therapy were also valued. BENEFITS AND COSTS: The benefits of successfully treating sporotrichosis accrue primarily for the patient. Because this infection is not spread from person-to-person, public health aspects of treatment are of minor importance. Most forms of sporotrichosis are not life-threatening; thus, therapy is aimed at decreasing morbidity, improving quality of life, and allowing the patient to return to occupational and familial pursuits. (ABSTRACT TRUNCATED)

AIDS-Related Opportunistic Infections↗