Treatment of blastomycosis
- Robert W Bradsher, Jr, MD
Robert W Bradsher, Jr, MD
- Professor of Medicine
- University of Arkansas for Medical Sciences
Blastomycosis is a systemic pyogranulomatous infection, primarily involving the lungs, which arises after inhalation of the conidia of Blastomyces dermatitidis. Blastomycosis of the lung can be asymptomatic or manifest as acute or chronic pneumonia. Hematogenous dissemination occurs frequently; extrapulmonary disease of the skin, bones, and genitourinary system is common, but almost any organ can be involved.
Unlike acute histoplasmosis, for which treatment often is not necessary, most patients with blastomycosis require therapy. (See "Diagnosis and treatment of pulmonary histoplasmosis".)
The antifungal agents proven to be useful in the treatment of blastomycosis will be reviewed here. The approach is generally in keeping with the 2008 Infectious Diseases Society of America clinical practice guidelines for the treatment of blastomycosis (table 1) [1,2]. The mycology, pathogenesis, epidemiology, and clinical manifestations of blastomycosis are discussed separately. (See "Mycology, pathogenesis, and epidemiology of blastomycosis" and "Clinical manifestations and diagnosis of blastomycosis".)
Treatment options for patients with blastomycosis include amphotericin B or one of the azole drugs (usually itraconazole) . Several factors must be considered when deciding upon the appropriate regimen:
●The clinical form and severity of disease – All patients with extrapulmonary disease or progressive pulmonary disease require therapy:
- Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 2008; 46:1801.
- http://www.idsociety.org/Content.aspx?id=9088 (Accessed on May 22, 2008).
- Parker JD, Doto IL, Tosh FE. A decade of experience with blastomycosis and its treatment with amphotericin B. A National Communicable Disease Center Cooperative Mycoses Study. Am Rev Respir Dis 1969; 99:895.
- Clemons KV, Stevens DA. Comparative efficacies of amphotericin B lipid complex and amphotericin B deoxycholate suspension against murine blastomycosis. Antimicrob Agents Chemother 1991; 35:2144.
- Cook PP. Amphotericin B lipid complex for the treatment of recurrent blastomycosis of the brain in a patient previously treated with itraconazole. South Med J 2001; 94:548.
- Perfect JR. Treatment of non-Aspergillus moulds in immunocompromised patients, with amphotericin B lipid complex. Clin Infect Dis 2005; 40 Suppl 6:S401.
- Panicker J, Walsh T, Kamani N. Recurrent central nervous system blastomycosis in an immunocompetent child treated successfully with sequential liposomal amphotericin B and voriconazole. Pediatr Infect Dis J 2006; 25:377.
- Chowfin A, Tight R, Mitchell S. Recurrent blastomycosis of the central nervous system: case report and review. Clin Infect Dis 2000; 30:969.
- Bradsher RW. Histoplasmosis and blastomycosis. Clin Infect Dis 1996; 22 Suppl 2:S102.
- Chapman SW, Lin AC, Hendricks KA, et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect 1997; 12:219.
- Abernathy RS. Amphotericin therapy of North American blastomycosis. Antimicrob Agents Chemother (Bethesda) 1966; 6:208.
- Groll AH, Giri N, Petraitis V, et al. Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis 2000; 182:274.
- Treatment of blastomycosis and histoplasmosis with ketoconazole. Results of a prospective randomized clinical trial. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Ann Intern Med 1985; 103:861.
- Bradsher RW, Rice DC, Abernathy RS. Ketoconazole therapy for endemic blastomycosis. Ann Intern Med 1985; 103:872.
- US Food and Drug Administration. Nizoral (ketoconazole): Drug Safety Communication - Potentially fatal liver injury, risk of drug interactions and adrenal gland problems. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm362672.htm?source=govdelivery (Accessed on July 26, 2013).
- Dismukes WE, Bradsher RW Jr, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med 1992; 93:489.
- Bradsher RW. Blastomycosis. Clin Infect Dis 1992; 14 Suppl 1:S82.
- Pappas PG, Bradsher RW, Chapman SW, et al. Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1995; 20:267.
- Pappas PG, Bradsher RW, Kauffman CA, et al. Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1997; 25:200.
- Li RK, Ciblak MA, Nordoff N, et al. In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. Antimicrob Agents Chemother 2000; 44:1734.
- Sugar AM, Liu XP. Efficacy of voriconazole in treatment of murine pulmonary blastomycosis. Antimicrob Agents Chemother 2001; 45:601.
- Freifeld A, Proia LA, Andes D, et al. Voriconazole use for endemic fungal infections [abstract 572]. In: Program and abstracts of the 44th Annual Meeting of the Infectious Diseases Society of America (Toronto, Canada). Alexandria, VA, Infectious Diseases Society of America, 2006:157.
- Bakleh M, Aksamit AJ, Tleyjeh IM, Marshall WF. Successful treatment of cerebral blastomycosis with voriconazole. Clin Infect Dis 2005; 40:e69.
- Borgia SM, Fuller JD, Sarabia A, El-Helou P. Cerebral blastomycosis: a case series incorporating voriconazole in the treatment regimen. Med Mycol 2006; 44:659.
- Lutsar I, Roffey S, Troke P. Voriconazole concentrations in the cerebrospinal fluid and brain tissue of guinea pigs and immunocompromised patients. Clin Infect Dis 2003; 37:728.
- Bariola JR, Perry P, Pappas PG, et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis 2010; 50:797.
- Sugar AM, Liu XP. In vitro and in vivo activities of SCH 56592 against Blastomyces dermatitidis. Antimicrob Agents Chemother 1996; 40:1314.
- Proia LA, Harnisch DO. Successful use of posaconazole for treatment of blastomycosis. Antimicrob Agents Chemother 2012; 56:4029.
- Miceli MH, Kauffman CA. Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent. Clin Infect Dis 2015; 61:1558.
- Espinel-Ingroff A. Comparison of In vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol 1998; 36:2950.
- Zhanel GG, Karlowsky JA, Harding GA, et al. In vitro activity of a new semisynthetic echinocandin, LY-303366, against systemic isolates of Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus species. Antimicrob Agents Chemother 1997; 41:863.
- Nakai T, Uno J, Ikeda F, et al. In vitro antifungal activity of Micafungin (FK463) against dimorphic fungi: comparison of yeast-like and mycelial forms. Antimicrob Agents Chemother 2003; 47:1376.
- Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183:96.
- Meyer KC, McManus EJ, Maki DG. Overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome. N Engl J Med 1993; 329:1231.
- Lemos LB, Baliga M, Guo M. Acute respiratory distress syndrome and blastomycosis: presentation of nine cases and review of the literature. Ann Diagn Pathol 2001; 5:1.
- Lahm T, Neese S, Thornburg AT, et al. Corticosteroids for blastomycosis-induced ARDS: a report of two patients and review of the literature. Chest 2008; 133:1478.
- Castillo CG, Kauffman CA, Miceli MH. Blastomycosis. Infect Dis Clin North Am 2016; 30:247.
- Sarosi GA, Davies SF, Phillips JR. Self-limited blastomycosis: a report of 39 cases. Semin Respir Infect 1986; 1:40.
- Johnson MD, Perfect JR. Fungal Infections of the Bones and Joints. Curr Infect Dis Rep 2001; 3:450.
- Lentnek AL, Lentnek IA. Successful management of Blastomyces dermatitidis meningitis. Infect Med 2006; 23:39.
- Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994; 330:263.
- Taillan B, Ferrari E, Cosnefroy JY, et al. Favourable outcome of blastomycosis of the brain stem with fluconazole and flucytosine treatment. Ann Med 1992; 24:71.
- Pearson GJ, Chin TW, Fong IW. Case report: treatment of blastomycosis with fluconazole. Am J Med Sci 1992; 303:313.
- Harley WB, Lomis M, Haas DW. Marked polymorphonuclear pleocytosis due to blastomycotic meningitis: case report and review. Clin Infect Dis 1994; 18:816.
- Szeder V, Ortega-Gutierrez S, Frank M, Jaradeh SS. CNS blastomycosis in a young man working in fields after Hurricane Katrina. Neurology 2007; 68:1746.
- Pappas PG, Pottage JC, Powderly WG, et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1992; 116:847.
- Pappas PG, Threlkeld MG, Bedsole GD, et al. Blastomycosis in immunocompromised patients. Medicine (Baltimore) 1993; 72:311.
- Serody JS, Mill MR, Detterbeck FC, et al. Blastomycosis in transplant recipients: report of a case and review. Clin Infect Dis 1993; 16:54.
- Recht LD, Davies SF, Eckman MR, Sarosi GA. Blastomycosis in immunosuppressed patients. Am Rev Respir Dis 1982; 125:359.
- Butka BJ, Bennett SR, Johnson AC. Disseminated inoculation blastomycosis in a renal transplant recipient. Am Rev Respir Dis 1984; 130:1180.
- Linden P, Williams P, Chan KM. Efficacy and safety of amphotericin B lipid complex injection (ABLC) in solid-organ transplant recipients with invasive fungal infections. Clin Transplant 2000; 14:329.
- Greene NB, Baughman RP, Kim CK, Roselle GA. Failure of ketoconazole in an immunosuppressed patient with pulmonary blastomycosis. Chest 1985; 88:640.
- Goldman M, Zackin R, Fichtenbaum CJ, et al. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis 2004; 38:1485.
- Schutze GE, Hickerson SL, Fortin EM, et al. Blastomycosis in children. Clin Infect Dis 1996; 22:496.
- Morris SK, Brophy J, Richardson SE, et al. Blastomycosis in Ontario, 1994-2003. Emerg Infect Dis 2006; 12:274.
- GENERAL APPROACH
- STUDIES OF ANTIFUNGALS
- Amphotericin B
- - Ketoconazole
- - Itraconazole
- - Fluconazole
- - Voriconazole
- - Other azoles
- CHOICE OF THERAPY
- Pulmonary blastomycosis
- - Moderately severe to severe
- - Mild to moderate
- Disseminated blastomycosis
- - Moderately severe to severe disseminated
- - Mild to moderate disseminated
- - Central nervous system
- Immunocompromised hosts
- SUMMARY AND RECOMMENDATIONS