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PubMed1998

Neck mass resulting from local extension of pulmonary blastomycosis.

Blastomycosis is an endemic systemic fungal infection that usually involves the lungs and superficial skin. Although head and neck involvement has been reported in the literature, no previous cases of neck mass resulting from direct extension of a pulmonary lesion have been published. We encountered an immunocompetent 31-year-old woman with a rapidly enlarging subcutaneous neck mass and a chronic upper lung infiltrate. Imaging studies showed contiguity between both lesions. Blastomyces dermatitidis was recovered from the sputum, and typical yeast was observed in fungal stains of needle aspirate from the neck mass. The patient responded favorably to a 6-month course of itraconazole. Blastomycosis should be considered in patients with subcutaneous neck masses in areas where this disease is endemic.

Adult↗
PubMed2006

Recurrent central nervous system blastomycosis in an immunocompetent child treated successfully with sequential liposomal amphotericin B and voriconazole.

Central nervous system involvement in infection with Blastomyces dermatitidis is uncommon, except in immunocompromised patients. We report a case of central nervous system blastomycosis occurring 18 months after treatment of pulmonary blastomycosis in an immunocompetent child. Our patient was successfully treated sequentially with liposomal amphotericin B followed by oral voriconazole without need for surgical resection.

Adolescent↗
PubMed2006

Disseminated blastomycosis in an infant.

Blastomycosis is an uncommon life-threatening disease caused by the dimorphic fungus Blastomyces dermatitidis. Estimates of the percentage of cases occurring in children range from 2% to 11%, and it is exceedingly rare in individuals less than 1 year of age. We present the case of an otherwise healthy infant with disseminated blastomycosis acquired in Northern Ontario and a brief review of the pediatric literature.

Amphotericin B↗
PubMed1989

Blastomycosis in Namibia--report of a case successfully treated with itraconazole.

The clinical, histological, mycological, radiological and scintigraphic features of a 42-year-old Namibian male with blastomycosis are described. This appears to be the first documented incidence of blastomycosis in Namibia. Leucocyte myeloperoxidase deficiency was evident. Treatment with itraconazole led to dramatic resolution of lesions. A reactive xanthogranulomatous response was present in a healed clavicular lesion.

Adult↗
PubMed1980

Laryngeal presentation of blastomycosis.

Systemic blastomycosis may rarely involve the larynx, and it most likely is a result of hematogenous dissemination or direct inoculation from a currently or previously active pulmonary infection. Often, laryngeal blastomycosis has been confused with squamous cell carcinoma because of the clinical and histopathologic similarities, and this confusion has led to inaccurate diagnosis and inappropriate therapy. The etiologic agent, Blastomyces dermatiditis, may be seen in infected tissue with routine and special stains; however, cultural proof remains the sine qua non for diagnosis.

Adult↗
PubMed2004

Localized blastomycosis-like pyoderma with good response to cotrimoxazol and cryotherapy.

Blastomycosis-like pyoderma is an unusual, exaggerated, vegetative-tissue reaction to a prolonged primary or secondary bacterial infection. It is a rare disease, usually seen in immunocompromized patients. We report a case of localized blastomycosis-like pyoderma responding poorly to classic treatments, but that gave a dramatic response to a combination treatment of cotrimoxazol and cryotherapy.

Aged↗
PubMed2005

Blastomycosis-like pyoderma: successful treatment with low-dose acitretin.

Blastomycosis-like pyoderma typically presents as verrucous plaque(s) with a purulent discharge through multiple sinuses. Two patients with blastomycosis-like pyoderma developing on significantly sun-damaged skin are presented: an 84-year-old man with multiple painful nodules and plaques, and a 92-year-old woman with a solitary plaque on the left calf. Histopathology showed pseudoepitheliomatous hyperplasia with dermal foci of suppuration. Staphylococcus aureus was isolated from a biopsy specimen in the first patient, whereas the latter patient had Prevotella and Corynebacterium species. Investigations for fungi and mycobacteria yielded negative results. These microbiological findings further supported the clinicopathological diagnosis. Both patients failed to respond to oral doxycycline despite the in vitro susceptibility of the organisms. Treatment with low-dose oral acitretin was successful in both patients after 3-4 months.

Acitretin↗
PubMedDate not supplied

Chronic disseminated cutaneous blastomycosis in an 11-year old, with a brief review of the literature.

Chronic disseminated cutaneous blastomycosis is rare in children. We discuss an 11-year-old immunocompetent boy who presented with a history of persistent and multiple skin lesions of >1 year's duration. These lesions proved to be secondary to chronic Blastomyces dermatitidis infection. Complete resolution of clinical disease occurred after a 6-month course of oral itraconazole. We also present a brief review of the literature focusing on the epidemiology, manifestations, diagnosis, and treatment of pediatric blastomycosis.

Blastomycosis↗
PubMedDate not supplied

Treatment of blastomycosis with itraconazole in 112 dogs.

One hundred twelve client-owned dogs with blastomycosis were treated with itraconazole, 5 or 10 mg/kg/d. The first group of 70 dogs treated in 1987 and 1988 received 10 mg/kg/d (group 1), and the second group of 42 dogs treated after October 1988 received 5 mg/kg/d (group 2). Even though the groups were treated at different times, the dogs were similar in age and gender distribution, number of sites involved, and percent and severity of pulmonary involvement. The proportion of dogs cured with a 60-day course of itraconazole was similar for both groups (53.6% versus 54.3%) and for a second historical control group treated with amphotericin B (57%); the recurrence rate was also similar, 20%, 21.4%, and 20%, respectively. Dogs treated with itraconazole had similar mortality rates (25.7% at 5 mg/kg/d; 25% at 10 mg/kg/day) to those treated with amphotericin B (23%). Seventeen of the 23 dogs that died (74%), did so during the first week of treatment; these early deaths were usually attributed to respiratory failure. The only site of infection that was significantly associated with failure (death or recurrence) was the brain. There was a marked difference in survival times between dogs without lung disease or with mild lung disease compared with dogs with moderate or severe lung disease. Serum itraconazole concentrations reached steady state by 14 days of treatment. Dogs receiving 5 mg/kg/d of itraconazole (group 2) had mean serum concentrations of 3.55 +/- 2.81 mg/mL (range, 0.67 to 10.8 micrograms/mL), whereas dogs receiving 10 micrograms/kg/d (group 1) had mean concentrations of 13.46 +/- 8.49 micrograms/mL (range, 1.8 to 28 micrograms/mL) (P < or = .001). There was no association between cure and serum itraconazole concentrations. Dogs in group 1 had significantly more adverse effects than dogs in group 2 (P = .046). Anorexia was the most common adverse effect, occurring in 14.9% of dogs in group 1. Only 8% of dogs in group 2 had adverse effects. Serum concentrations of itraconazole were positively correlated with serum alkaline phosphatase and alanine aminotransferase activities. Our findings indicate that itraconazole administered at a dose of 5 mg/kg/d is the drug of choice for blastomycosis in dogs.

Alanine Transaminase↗
PubMedDate not supplied

Comparison of enzyme immunoassay and immunodiffusion for the detection of canine blastomycosis.

Two Blastomyces dermatitidis commercial immunodiffusion antigens, Meridian Diagnostics and Nolan-Scott Laboratories, and two B. dermatitidis yeast phase lysate antigens, T-58 and K-Le, prepared in our laboratory were utilized in an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies in 61 serum specimens from dogs with blastomycosis. All antigens used in the ELISA were diluted to 50 ng of protein ml-1. Immunodiffusion (ID) tests were also performed on the sera using a Nolan-Scott ID antigen. Greater reactivity, based on the ELISA index value, was evidenced with the two yeast phase lysate antigens over the two commercial reagents in the ELISA. In addition the sensitivity of the ELISA with the T-58, K-Le and Meridian antigens was considerably greater than that of the ID test. The Nolan-Scott antigen, however, was able to detect more positive specimens when used in the ID procedure than in the ELISA. Therefore encouraging results were obtained with respect to the continued development and optimization of the ELISA using B. dermatitidis cell lysate antigens for the diagnosis of blastomycosis.

Animals↗
PubMed1990

Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis.

Nikkomycins X and Z, competitive inhibitors of fungal chitin synthase, were evaluated as therapeutic agents in vitro and in mouse models of coccidioidomycosis, histoplasmosis, and blastomycosis. In vitro, the nikkomycins were found to be most effective against the highly chitinous, dimorphic fungi Coccidioides immitis and Blastomyces dermatitidis, were less effective against yeasts, and were virtually without effect on the filamentous fungus Aspergillus fumigatus. Additionally, by transmission electron microscopy, nikkomycin Z was highly disruptive to the cell wall and internal structure of the spherule-endospore phase of C. immitis in vitro. In vivo, nikkomycin Z was more effective than nikkomycin X, was also found to be superior on a milligram per milligram basis to the majority of azoles tested in the models of coccidioidomycosis and blastomycosis, and was moderately effective in histoplasmosis. A study of the pharmacokinetics in mice showed that nikkomycin Z was rapidly eliminated after intravenous infusion but that absorption after oral administration was sufficiently slow to allow inhibitory levels to persist for more than 2 h. Results of limited toxicology tests suggest that nikkomycin Z was well tolerated at the dosages employed.

Administration, Oral↗
PubMed1990

Therapeutic effect of the triazole Bay R 3783 in mouse models of coccidioidomycosis, blastomycosis, and histoplasmosis.

A new triazole, Bay R 3783, was compared with ketoconazole, itraconazole, and fluconazole, which were given via the alimentary tract at three dosages, and amphotericin B, which was given at 1 mg/kg intraperitoneally, in murine models of the systemic mycoses coccidioidomycosis, histoplasmosis, and blastomycosis. In a pulmonary coccidioidomycosis model, Bay R 3783, fluconazole, and itraconazole were essentially equally efficacious and more active than ketoconazole in protecting mice against death; but they were inferior to amphotericin B. In a short-term organ load experiment, Bay R 3783 and amphotericin B were equally effective and were more effective than the other drugs in reducing the amount of Coccidioides immitis in the lungs. Against meningocerebral coccidioidomycosis, Bay R 3783, itraconazole, and fluconazole at 25 mg/kg and amphotericin B prevented death only during therapy, with mortalities ensuing shortly thereafter. In mice with systemic histoplasmosis, Bay R 3783 and itraconazole at 25 mg/kg and amphotericin B prevented death in all mice through a 44-day observation period. Clearance of Histoplasma capsulatum from organs was similar in mice treated with Bay R 3783 and itraconazole; this clearance was greater than that in mice treated with ketoconazole and fluconazole but less than that in mice treated with amphotericin B. In mice with systemic blastomycosis, Bay R 3783 at 25 mg/kg yielded 90% survivors at 60 days, which was greater than that achieved with amphotericin B (60%) or itraconazole (30%). Clearance of Blastomyces dermatitidis from the lungs was greatest with Bay R 3783, followed by that with amphotericin B, itraconazole, fluconazole, and ketoconazole, in that order. Therefore, Bay R 3783 showed effectiveness comparable to or exceeding those of itraconazole and fluconazole and exceeding that of ketoconazole against these systemic mycoses in mice.

Animals↗
PubMed1991

Comparative efficacies of amphotericin B lipid complex and amphotericin B deoxycholate suspension against murine blastomycosis.

Amphotericin B as a lipid complex and as a deoxycholate suspension (Fungizone) was tested against murine blastomycosis. All doses of each form prolonged survival (P less than 0.05 to 0.001). Fungizone was more effective than lipid complex at doses of 0.8 mg/kg of body weight. However, lipid complex at 12.8 mg/kg was not toxic and superior in efficacy (P less than 0.001) to 2.0 mg of Fungizone per kg (a toxic dose), and it cleared all animals of infection. Lipid complex is an effective therapy for murine blastomycosis.

Amphotericin B↗
PubMed1995

Treatment of murine pulmonary blastomycosis with SCH 51048, a broad-spectrum triazole antifungal agent.

The in vitro and in vivo activities of a new broad-spectrum triazole derivative, SCH 51048, against Blastomyces dermatitidis were evaluated. As determined by using the new National Committee for Clinical Laboratory Standards proposed standard for susceptibility testing of yeasts, SCH 51048 was the most active of the four agents tested in vitro against 13 strains of B. dermatitidis. In a well-described murine model of acute pulmonary blastomycosis, SCH 51048 was comparable to amphotericin B and at least 30 times more active than itraconazole. On the basis of these experiments, clinical evaluation of SCH 51048 for the use in treatment of human blastomycosis should proceed.

Animals↗
PubMed1997

Efficacy of nikkomycin Z against experimental pulmonary blastomycosis.

Nikkomycin Z is a chitin synthetase inhibitor. In vitro, nikkomycin Z had good activity against Blastomyces dermatitidis, with an MIC of 0.78 microg/ml and a minimal fungicidal concentration of 3.1 microg/ml. The efficacies of various treatment durations (3, 5, or 10 days) and doses (200, 400, or 1,000 mg/kg of body weight) of nikkomycin Z given twice daily were compared with those of itraconazole at 200 mg/kg given twice daily and amphotericin B at 6.25 mg/kg in a murine model of pulmonary blastomycosis. All treatments prolonged survival compared with untreated controls (P < 0.05 to 0.01); 100% survival was achieved with 5 or 10 days of any nikkomycin Z dose or with amphotericin B. Amphotericin B and nikkomycin Z, but not itraconazole, reduced infection compared with controls. Amphotericin B and the 10-day regimens of all nikkomycin Z doses were equivalent and superior to itraconazole or nikkomycin Z for < or = 5 days at any dose (P < 0.05 to 0.01). Increased duration and/or dosage improved the efficacy of nikkomycin Z, with 10 days of each dose curing 50 to 90% of the animals. Only a 1,000-mg/kg/day dose of nikkomycin Z was curative when treatment lasted less than 10 days. In contrast, itraconazole cured no mice, while amphotericin B cured all mice. Based on the total amount of drug given, amphotericin B was estimated to be 32 times as active as nikkomycin Z and nikkomycin Z was estimated to be 3 times as active as itraconazole. Overall, nikkomycin Z given orally was well tolerated, had good activity against blastomycosis, and could result in biological cure, thus producing results equivalent to those of parenteral amphotericin B.

Aminoglycosides↗
PubMed2001

Efficacy of voriconazole in treatment of murine pulmonary blastomycosis.

We evaluated the efficacy of voriconazole, a new broad-spectrum triazole antifungal compound, in the treatment of murine pulmonary blastomycosis. Since mice metabolize voriconazole rapidly, we took advantage of our previous observation that administration of grapefruit juice to mice resulted in suitable serum voriconazole concentrations so that treatment studies with mice could be done (A. M. Sugar and X.-P. Liu, Med. Mycol. 38:209-121, 2000). Our results show that voriconazole prolonged survival in a dose-dependent fashion and that the fungal burden in the lungs was decreased by voriconazole administered at 40 mg/kg of body weight/day. Voriconazole should be studied in humans with blastomycosis.

Animals↗
PubMed1985

Evolution of inflammatory response and cellular immune responses in a murine model of disseminated blastomycosis.

A reproducible model of disseminated blastomycosis was established in C57BL/6 mice by intravenous injection of 10(6) yeast-phase Blastomyces dermatiditis organisms. The infection progressed over 5 weeks to involve lungs, brains, superficial fascia, livers, and spleens of mice. By week 5, there was a greater number of organisms in lungs and brains than in livers and spleens. The tissue response in lungs, brains, and livers progressed from acute neutrophilic invasion before week 1 to pyogranuloma formation by week 5. Lymph nodes and spleens were remarkably spared. By week 5, infected mice became anergic to intradermal challenge with both specific Blastomyces antigen and a nonspecific antigen (sheep erythrocytes). At this time, the response to concanavalin A or phytohemagglutinin by splenocytes was markedly less than that of normal controls. Likewise, the plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice was diminished. In coculture studies, splenocytes from 5-week-infected mice reduced the plaque-forming cell response by normal splenocytes. The development of this murine model should prove useful for elucidating the perturbations of immunoregulation associated with disseminated blastomycosis.

Animals↗
PubMed2000

Correlation of susceptibility of immature mice to fungal infection (blastomycosis) and effector cell function.

Immature mice are highly susceptible to blastomycosis, which is similar to other mycoses and has parallels in humans. The murine susceptibility is noteworthy in that it persists beyond the development of resistance to other, nonfungal pathogens and the maturation of most immune functions. As the susceptibility to blastomycosis appeared to be related to an early event after infection, primary effector cell function was studied. We found that peritoneal inflammatory cells, enriched for neutrophils, from immature (3-week-old) mice killed nonphagocytizable Blastomyces dermatitidis cells less (25%) than did cells from mature (8-week) mice (70%) (P<0.01), a defect intrinsic to the neutrophils. This correlated with an impaired immature cell oxidative burst. Killing of phagocytizable Candida albicans was not significantly different, 73 versus 87%. Thioglycolate-elicited cells were more impaired; killing of B. dermatitidis was insignificant, and killing of C. albicans was more impaired in immature (16% killing) than in mature (45%) cells (P<0.02). Peripheral blood neutrophils from mature animals killed B. dermatitidis (41%) more than did those from immature animals (10%) (P<0.02); C. albicans was killed efficiently by both. Resting or activated peritoneal macrophages from both types of animals showed no differences in B. dermatitidis killing. These results suggest that the susceptibility of immature mice is related at least in part to the depressed capacity of their neutrophils to kill B. dermatitidis.

Age Factors↗