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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↗

Blastomycosis in nondomestic felids.

Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.

Acinonyx↗

Pulmonary blastomycosis: findings on chest radiographs in 63 patients.

Posteroanterior and lateral chest radiographs of 63 patients with proved pulmonary blastomycosis were evaluated to determine the most common findings. Included in the analysis were the location of the pulmonary infiltrates, the distribution and parenchymal patterns of disease, and the prevalence of adenopathy, pleural effusions, and/or cavity formation. Blastomycosis pneumonitis involved more than one pulmonary lobe in 21 patients and a single upper lobe in 27 of 63 patients. Forty-eight of the 63 patients had air-space consolidation. In nine of the 63 patients, a pulmonary mass was the major abnormality seen on radiographs. Approximately one fifth of the patients had associated pleural effusions and/or mediastinal or hilar adenopathy. Twenty-three patients (37%) had cavitation within the area of pulmonary consolidation. These findings suggest that blastomycosis should be considered when chest radiographs show air-space infiltrate in the upper lobes or in more than one lobe of the lung, especially when the infiltrate is associated with pleural effusions, cavitation, lymphadenopathy, and/or a paramediastinal mass.

Adult↗

Pulmonary blastomycosis in children: findings on chest radiographs.

OBJECTIVE: The purpose of this study was to identify characteristic radiographic findings in children with pulmonary blastomycosis. SUBJECTS AND METHODS: We reviewed the charts and radiographs of 18 children with culture-proven acute pulmonary blastomycosis. The 10 boys and eight girls were from 1 to 16 years old. Sixteen were Native Canadian Indians, and two were white. All available chest radiographs, including those obtained in follow-up after treatment was terminated, were reviewed by a pediatric radiologist. Consolidation was classified by location and extent, and other abnormalities were noted. RESULTS: Initial chest radiographs showed consolidation in 16 patients. Seven patients had single lobe involvement, most commonly of the left lower lobe. Nine patients had multiple lobe involvement. The left lower lobe was most commonly involved in these cases, but the middle lobe was most severely affected. The upper lobes were involved only in children with multiple lobe disease and were only mildly affected. Cavitation developed in two patients, followed by bronchogenic spread of the disease. Pleural effusions were seen in three patients; two also had rib lesions. Hilar adenopathy developed in two children. Five patients had radiographs available, which had been obtained more than a year after onset, and three of these were abnormal. CONCLUSION: The most common radiologic finding in children with pulmonary blastomycosis is pulmonary consolidation in one or several lobes, which may undergo cavitation. Lymphadenopathy and pleural effusions are uncommon. Chronic abnormalities may develop.

Acute Disease↗

Blastomycosis in Ontario, 1994-2003.

We describe a case of blastomycosis in an 8-year-old boy with Blastomyces-associated osteomyelitis and possible pulmonary involvement. We also identify 309 cases of blastomycosis in Ontario that were seen during a 10-year period, 57% of which occurred from 2001 to 2003. The overall incidence during the study period was 0.30 cases per 100,000 population. Most patients were from north Ontario (n = 188), where the incidence was 2.44 cases per 100,000. The incidence in the Toronto region was 0.29 per 100,000. Thirteen percent of cases occurred in children <19 years of age. These findings substantially increase the number of known cases in Ontario and Canada. Clinicians may encounter persons infected with Blastomyces dermatitidis and must be familiar with its signs and symptoms and be aware of locations, such as northwestern Ontario, where disease is endemic or hyperendemic. We advocate resuming blastomycosis as a reportable disease in Ontario to facilitate tracking cases.

Adolescent↗

Calcinosis cutis associated with systemic blastomycosis in three dogs.

Three dogs treated for systemic blastomycosis with intravenous amphotericin B (one case) or amphotericin B lipid complex (two cases) developed mild to severe calcinosis cutis two to six weeks after the initiation of treatment. Abnormalities in serum calcium and phosphorus during treatment for blastomycosis or at the time of diagnosis of calcinosis cutis were slight or absent. The calcification was not associated with lesions of cutaneous blastomycosis. Calcification was limited to the skin in two cases and may have also involved the kidneys in one. The calcinosis cutis resolved completely in all three dogs with no (two cases) or only palliative (one case) therapy.

Animals↗

Ketoconazole therapy for endemic blastomycosis.

Amphotericin B is effective in therapy for blastomycosis but causes a number of serious adverse reactions. Because ketoconazole has in-vitro activity against Blastomyces dermatitidis, we administered this agent in a dosage of 400 mg/d to 46 patients with blastomycosis, with 43 patients receiving at least 1 month of therapy. Thirty-five patients had cure without relapse over a mean follow-up of 17 months. Six had a relapse of infection but 4 of these had been noncompliant with therapy. Two patients improved initially but ultimately had progression of disease despite maintenance of adequate serum levels. Adverse effects were common but not severe. Three patients with extensive infection died--2 had received only one dose of ketoconazole and 1 had received therapy for only 2 weeks. The cure rate in these patients suggests that ketoconazole may replace amphotericin B as the initial treatment of blastomycosis that is not overwhelming.

Adult↗

Cutaneous blastomycosis in New Brunswick: case report.

Blastomycosis is a fungal infection of immunocompetent hosts. We present a case of cutaneous blastomycosis acquired in New Brunswick, which provides evidence that this disease is endemic in Atlantic Canada. This case also demonstrates that the diagnosis of blastomycosis may be elusive. Perseverance, a high index of clinical suspicion and close cooperation with the microbiology laboratory may be required to diagnose this uncommon condition.

Blastomycosis↗

Acquired immunodeficiency syndrome-related blastomycosis in an unusual geographic location.

Blastomycosis is a fungal infection acquired via inhalation of Blastomyces dermatitidis. The majority of cases occur in central, southeastern, and mid-Atlantic areas of the United States. We report the case of a 42-year-old veteran infected with the human immunodeficiency virus who presented in E1 Paso, Texas, with a dry cough, fever, and recent weight loss. We review the clinical and epidemiologic features of blastomycosis. Diagnostic criteria and pharmacologic management are discussed. Active duty personnel are at high risk of exposure to B. dermatitidis. Military providers should maintain an index of suspicion for blastomycosis in endemic and nonendemic regions.

AIDS-Related Opportunistic Infections↗

Cutaneous blastomycosis without evidence of pulmonary involvement.

Blastomycosis is an infection that is often associated with recent military, occupational, or recreational activities near damp soil in various endemic regions, including the Great Lakes and major river valleys in the Midwest as well as various overseas regions. In the great majority of cases, the disease presents as a primary pulmonary disease with or without extrapulmonary involvement. We present a case of cutaneous blastomycosis with no evidence of pulmonary or other systemic involvement. With such presentations, the disease is presumed to have spread hematogenously with the asymptomatic or minimal primary pulmonary infection having resolved spontaneously. The patient's diagnosis was made with positive cultures and histologic examinations revealing features that are quite characteristic of blastomycosis. The patient responded to treatment with itraconazole for 6 months with no recurrence after 1 year. A high index of suspicion must be maintained when evaluating patients with progressive ulcerating or verrucous lesions that do not respond to traditional antibiotic therapy, especially with a history of recent activities in the endemic regions.

Adult↗

Blastomycosis presenting as recurrent tender cutaneous nodules.

Blastomycosis is caused by inhalation of airborne spores from Blastomyces dermatitidis, a dimorphic fungus found in soil. It is endemic in the southeastern, Midwestern, and south central states of North America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and disseminated disease. Definitive diagnosis is based on identification of the characteristic thick-walled, broad-based budding yeasts by direct examination of tissue or the isolation of Blastomyces in culture. Itraconazole is the treatment of choice for mild to moderate pulmonary disease. Amphotericin B is the first line agent in life-threatening disseminated disease, central nervous system involvement, acute respiratory distress syndrome, pregnancy, immunocompromised states, and in those who cannot tolerate or fail azole therapy. We report a case of blastomycosis presenting as a fever of unknown etiology and recurrent skin nodules.

Adult↗

Peritoneal blastomycosis.

Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis. Involvement of the peritoneum is unusual, with only two previously reported cases that occurred in association with disseminated disease. A single case of histopathologically proven blastomycosis involving the peritoneum is presented, as well as a short overview of previously published cases on gastrointestinal and peritoneal blastomycosis. The case is unique in that chronic peritonitis was the only manifestation of disease. The diagnosis was made by laparoscopy.

Adult↗

North American blastomycosis.

Pulmonary blastomycosis may present as a mass that resembles a lung tumor on radiographs. Blastomycosis should be suspected if the patient has an associated skin lesion and known risk factors, such as living in or visiting endemic areas or participating in activities that involve frequent contact with soil. If these risk factors are kept in mind, the diagnosis of blastomycosis may be established before a thoracotomy is performed unnecessarily.

Amphotericin B↗

Treatment of blastomycosis and histoplasmosis with ketoconazole. Results of a prospective randomized clinical trial. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

In a multicenter prospective randomized trial, the efficacy and toxicity of low-dose (400 mg/d) and high-dose (800 mg/d) oral ketoconazole were compared in 80 patients with blastomycosis and in 54 with histoplasmosis. Among 65 patients with blastomycosis treated for 6 months or more, high-dose treatment was more effective (100% success rate compared with 79%; p = 0.001). Among 19 patients with chronic cavitary histoplasmosis treated for 6 months or more, both regimens were equally effective (overall success rate, 84%). In 20 patients with localized or disseminated histoplasmosis treated for 6 months or more, low-dose treatment was more effective (100% success rate compared with 57%; p = 0.03). The success rate for all patients with histoplasmosis treated for 6 months or more was 85%. Adverse effects occurred in 81 of 134 patients (60%) and were commoner with the high-dose regimen. Ketoconazole is effective for immunocompetent patients with non-life-threatening, nonmeningeal forms of blastomycosis and histoplasmosis. Because of the higher frequency of side effects associated with the high dose, ketoconazole therapy should be initiated with the low dose.

Adult↗

Systemic fungal infections: diagnosis and treatment. I. Blastomycosis.

Blastomycosis is a rare systemic fungal infection caused by Blastomyces dermatitidis, which is often difficult to diagnose because of its spectrum of manifestations, varying severity, and unusual occurrence in most geographic areas. Because routine serologic methods and skin tests are not reliable for this pathogen, diagnosis is made by visualization of the organism in tissue, sputum, or exudate, or by culture. Once blastomycosis is diagnosed, therapeutic options include treatment with amphotericin B or ketoconazole, or simple observation if spontaneous resolution is anticipated. The purpose of this discussion is to review the features of blastomycosis that relate to the clinical practice of medicine.

Antifungal Agents↗

Blastomycosis in a ferret.

An 18-month-old female ferret with an ulcerated metacarpal pad and signs of respiratory illness was diagnosed as having blastomycosis by visualization of organisms on a tissue imprint, an agarose gel immunodiffusion test, and thoracic radiography. The ferret was treated intravenously with amphotercin B at 0.4 to 0.8 mg/kg and orally with ketoconazole at 8 mg/kg for approximately 1 month, during which time clinical and radiographic improvement was noted. A change to SC amphoterocin B therapy resulted in relapse of clinical signs despite continuation of ketoconazole therapy, and necessitated euthanasia. Necropsy revealed granulomatous lesions typical of Blastomyces dermatitidis infection in the lungs, thoracic pleura, spleen, meninges, and brain. Comparisons between this case and canine blastomycosis cases are made and alternative treatment regimes for mustelid blastomycosis are suggested.

Amphotericin B↗

Treatment of canine blastomycosis with ketoconazole.

Four dogs with blastomycosis were treated with ketoconazole, and good results were obtained in 3 of the 4 cases. Dogs that responded to treatment had manifested a variety of the clinical forms of blastomycosis (osseous, pulmonary, lymphatic, and ocular), and all lesions in the dogs abated. There were no clinical signs or clinicopathologic evidence of adverse drug reaction or toxicosis. The results of the study suggested that ketoconazole is effective for the treatment of canine blastomycosis.

Animals↗

The epidemiology and ecology of blastomycosis, coccidioidomycosis and histoplasmosis.

Blastomycosis, coccidioidomycosis and histoplasmosis are the major pulmonary mycoses of humans. Each is considered to be a primary pulmonary disease acquired by inhalation of infectious spores from the environment. Blastomycosis occurs predominantly in the Mississippi River Valley and Southeastern portions of the U.S.A. Clinical cases have also been noted from a few other areas of the world. The etiologic agent, Blastomyces dermatitidis, is not readily recoverable from nature, but the disease is not contagious and must be acquired from some exogenous source poorly defined at present. Blastomycosis is common in dogs but unusual in other species although a wide variety of animals can be infected experimentally. The disease is more common in middle age, in blacks, and in males. Coccidioidomycosis is restricted to the Western Hemisphere where most cases occur in the semiarid regions of Southwestern U.S. and contiguous areas of Mexico. Limited endemic foci are found in South and Central American locations. The arthroconidia of Coccidioides immitis occur in the soil of endemic areas from whence they are inhaled by humans and other animals. The disease is not customarily contagious. Handling cultures in the laboratory is a serious biohazard. The basis for an apparent racial predisposition to develop disseminated disease is unknown. Two clinical entities distinguishable by their etiologic agents are recognized to comprise histoplasmosis. Histoplasmosis caused by Histoplasma capsulatum var. capsulatum is a cosmopolitan disease with the greatest known concentration of cases located in the eastern half of the U.S. and most of Latin America.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗