Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America.

Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening non-CNS blastomycosis.

Vertebral blastomycosis with paravertebral abscess: report of eight cases and review of the literature.

Bone is the third most frequent site of disease in patients with blastomycosis, and the vertebrae are among the bones affected most often. We describe the clinical features and treatment of eight patients with vertebral blastomycosis and review the literature regarding this disease. All eight patients had destructive vertebral lesions evident on radiographs, and all had clinical or radiographic evidence of a contiguous abscess. The lower thoracic or lumbar regions were affected most often. Fever and skin lesions typical of blastomycosis were variably present. All but one patient had an abnormal chest radiograph. Treatment included long-term antifungal therapy and drainage of large fluid collections. Five of the eight patients were cured of their disease. Of the other 3 patients, 1 is still receiving therapy and is probably cured, 1 died of blastomycosis, and the status of 1 is unknown. In areas of endemicity, blastomycosis should be a diagnostic consideration for any patient with a destructive vertebral lesion.

Clinical features of blastomycosis.

Blastomycosis is a uncommonly diagnosed but important fungal infection in the south-central and midwestern United States. Epidemics related to a point-source exposure includes patients of all ages and both sexes, but endemic cases are usually in young to middle-aged adults, more reported commonly in men than women. The infection may mimic many other more common illnesses. Pneumonia is the most common manifestation, and the lung is almost always the organ initially infected. Infection in the lung may present either mimicking a short term bacterial pneumonia or a more indolent and long-term condition like tuberculosis or lung cancer. Cutaneous disease is the most common site of extrapulmonary involvement and may present with verrucous or ulcerative lesions. Osseous, prostatic, and central nervous system involvement are next most frequent in descending order. In a patient from the proper endemic area, blastomycosis should be on the differential diagnostic list for lung, skin, and other organ system infection.

Therapy of blastomycosis.

Blastomycosis is a rare but important fungal infection that is diagnosed primarily in the south-central and midwestern United States. Although some patients have subclinical infection and are not treated, the majority of patients with a clinical diagnosis of blastomycosis are treated with antifungal agents. Amphotericin B is curative but, because of toxicity, oral agents have been examined as therapy. Ketoconazole was shown to be effective for less than overwhelming blastomycosis, but adverse effects were relatively common. Itraconazole is a triazole agent that is more effective than ketoconazole, because it is often effective when ketoconazole fails or after relapse of infection following a response to ketoconazole. Fluconazole is not as effective therapy for blastomycosis based on the need for much higher doses than with itraconazole. In a patient with lifethreatening or central nervous system blastomycosis, amphotericin B should be given.

Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

Recent clinical data suggest that fluconazole at daily doses of 200 to 400 mg for at least 6 months is moderately effective therapy for non-life-threatening blastomycosis. To examine the usefulness of higher doses of fluconazole therapy for this disorder, we conducted a multicenter, randomized, open-label study to determine the efficacy and safety of two different daily doses of fluconazole (400 and 800 mg) in the treatment of non-life-threatening blastomycosis. Of 39 patients evaluable for efficacy analysis, 34 (87%) were successfully treated, including 89% and 85% of patients who received 400 and 800 mg, respectively. Five (83%) of six patients for whom prior antifungal therapy had failed were successfully treated. The mean duration of therapy was 8.9 months for successfully treated patients. Nineteen patients (48%) reported adverse events, although most were minor. We conclude that fluconazole at daily doses of 400 to 800 mg for at least 6 months is effective therapy for non-life-threatening blastomycosis.

Histoplasmosis and blastomycosis.

Histoplasmosis and blastomycosis are caused by dimorphic fungi, can be epidemic or endemic, and can produce a spectrum of illness, from subclinical infection to progressive disseminated disease. Diagnosis of both is best made by visualization of yeast in tissue or by culture. Itraconazole is the drug of choice for treatment of both histoplasmosis and blastomycosis, except in cases of life-threatening infection, for which amphotericin B is indicated. A heavy inoculum of Histoplasma capsulatum may cause acute pulmonary infection in an otherwise healthy host, resulting in fever, hypoxia, and pulmonary infiltrates. Opportunistic histoplasmosis develops as chronic pulmonary histoplasmosis in those with a structural defect in the lung (emphysema) or as disseminated histoplasmosis in patients with cellular immune deficiency (due to immunosuppressants or AIDS). Blastomyces dermatitidis causes both pulmonary and extrapulmonary disease. Lung involvement may mimic bacterial pneumonia, while chronic presentations mimic lung cancer or tuberculosis. Skin is the most common extrapulmonary site of disease, followed by bone, prostate, and central nervous system.

Detection of specific antibodies in human blastomycosis by enzyme immunoassay.

Serologic tests for the diagnosis of blastomycosis have had inadequate sensitivity, but results are improved with enzyme immunoassay (EIA) with A-antigen of Blastomyces dermatitidis. The Premier Blastomyces EIA kit (Meridian Diagnostics Inc, Cincinnati, Ohio) detected antibody against the B dermatitidis A-antigen in sera from 104 of 125 patients (83%) with culture-proven blastomycosis. Semiquantitative index values (positivity multiplied by the dilution) ranged from 1.0 to 423.3; the degree of positivity correlated with disease activity. Immunodiffusion bands were infrequently detected, with positive specimens from only 19 (21%) of 92 patients with blastomycosis. In 8 of 24 patients with histoplasmosis, 24 of 51 specimens (47%) were positive for Blastomyces antibody by EIA; index values were lower, with a mean of 3.8 versus 24.3 for sera from patients with blastomycosis. Only 1 of 13 patients with other fungal infections had positive results with EIA. This EIA system provided better sensitivity than previously available commercial systems for serodiagnosis of blastomycosis.

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.

Safe administration of iron dextran to a patient who reacted to the test dose.

Parenteral iron therapy is infrequently required but generally well tolerated. We present a case in which intravenous iron dextran was successfully given to a patient who had an anaphylactoid reaction to the test dose. After pretreatment with methylprednisolone, diphenhydramine, ephedrine, and dextran 1, 2 g of iron dextran were safely given over several days; pretreatment was administered only on day 1. In the rare cases in which an anaphylactic agent must be given to a patient with a history of a life-threatening reaction to the agent, pretreatment along with slow escalation of dose may allow safe administration of the offending drug.

Haemophilus influenzae epididymo-orchitis and bacteremia in a man infected with the human immunodeficiency virus.

Haemophilus influenzae is a major bacterial pathogen in patients infected with the human immunodeficiency virus (HIV), although most infections with this organism occur in the respiratory tract. We describe an adult with HIV infection who presented with epididymo-orchitis due to H. influenzae. Eleven prior cases of H. influenzae epididymo-orchitis have been published, but all of these cases occurred in pediatric patients. Little is known about the prevalence of genitourinary tract infections caused by H. influenzae among adults. H. influenzae is a relatively rare cause of bacteremia in adults, but the frequency of H. influenzae bacteremia has been increasing among the HIV-positive population.

A clinician's view of blastomycosis.

In summary, blastomycosis is a rarely reported but important infection in certain endemic areas. Better understanding of the number with subclinical infection is dependent on studies with more reliable and specific immunologic testing. The illness may mimic several other conditions but particularly neoplastic disease. Therefore, fungal cultures and smears, which will allow a firm diagnosis, should be obtained during invasive procedures aimed at the diagnosis of cancer. Therapy of blastomycosis has been broadened with the addition of ketoconazole. Itraconazole appears to have even greater efficacy while fluconazole remains to be confirmed as an effective agent for this infection. The role of amphotericin B or itraconazole depends on comparative clinical trials.

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.

Blastomycosis.

Blastomycosis is a rare but important fungal infection that occurs primarily in the south central and midwestern United States. Epidemics of blastomycosis related to a point-source exposure include patients of all ages and both sexes; however, cases of endemic blastomycosis are usually in young to middle-aged adults and are reported more for men than for women. Pneumonia is the most common manifestation of blastomycosis, and the lungs are almost always the organ initially infected. Skin, bone, prostate, and central nervous system are the next most frequently infected organs in descending order. Amphotericin B is curative, but because of its toxic effects, oral agents have been investigated as therapy for blastomycosis. ketoconazole should replace amphotericin B as therapy for blastomycosis that is not life threatening. Itraconazole is an experimental agent that is perhaps even more effective than ketoconazole. The therapeutic usefulness of fluconazole for blastomycosis remains unproven. For patients with life-threatening or central nervous system blastomycosis, amphotericin B remains the treatment of choice.

Otitis media due to blastomycosis: report of two cases.

Blastomycosis as a causative agent in cases of otitis media has not previously been reported. Two patients recently presented with otitis media and head and neck masses due to Blastomyces dermatitidis. Initial evaluation suggested neoplastic disease, but biopsy confirmed a fungal etiology for the masses in both patients. Relapse after administration of ketoconazole was noted in one patient, who was an adult; the other patient was a child. Otitis media and masses of the head and neck are unusual features of blastomycosis. Blastomycosis should be considered in the differential diagnosis for patients with such mass lesions and for patients with otitis media.

Comparison of acridine orange stain with culture and gram stain of needle aspirate in experimental Pseudomonas pneumonia.

The sensitivity and specificity of culture, acridine orange stain, and Gram stain were determined using needle aspiration (NA) material obtained from 82 rats with acute Pseudomonas aeruginosa pneumonia and 18 control rats. Lungs were then processed for either bacterial quantitation or histopathologic examination. NA culture proved to be the most sensitive and specific (55 and 100%, respectively). Sensitivity of acridine orange stain was 40%, whereas Gram stain was only 29%. The specificity of each stain was at least 94%. Lung bacterial concentrations influenced the sensitivities of all three techniques, with better sensitivity found in NA samples obtained from lung with bacterial concentration of at least 10(4) colony-forming units (cfu) of P. aeruginosa. Acridine orange and Gram stain results were similar except in NA samples from lung with bacterial concentration of less than 10(4) cfu in which acridine orange stain was more sensitive. The presence of stains identifying bacteria collected from animals with sterile NA culture was found in a small but significant number of samples, suggesting the presence of nonviable though stainable organisms. Use of all three techniques (culture, acridine orange stain, and Gram stain) increased sensitivity to approximately 70% with minimal decrease of specificity.

Evidence of subclinical blastomycosis in forestry workers in northern Minnesota and northern Wisconsin.

PURPOSE: To investigate the incidence of remote subclinical blastomycosis in a high-risk population of forestry workers. PATIENTS AND METHODS: The study consisted of 39 male forestry workers from northern Minnesota and northern Wisconsin, areas endemic for blastomycosis but not for histoplasmosis. All subjects were histoplasmin skin test-negative, and none had ever been diagnosed with blastomycosis or pneumonia. An antigen-specific lymphocyte stimulation assay was performed to determine the presence of blastomycosis. RESULTS: Peripheral blood lymphocytes from 12 of 39 subjects demonstrated specific antigen-induced proliferation when stimulated with a purified alkali- and water-soluble antigen derived from the cell wall of Blastomyces dermatitidis. CONCLUSION: The finding that 30% of these men had evidence of previous blastomycosis suggests that subclinical cases do occur sporadically, and are probably more common than diagnosed symptomatic cases. This is similar to histoplasmosis, in which the majority of infections are subclinical. However, the reservoir of persons with previous undiagnosed blastomycosis is probably small compared to the huge number of persons (perhaps 30 million) with prior histoplasmosis.