Abstract
Blastomyces dermatitidis, a dimorphic fungus endemic to the Midwestern, South Central and Northeastern United States, causes the disease blastomycosis. Aerosolized spores from the environment are inhaled into the lungs where primary infection may be asymptomatic or subclinical. Pneumonia, the most common presentation of symptomatic blastomycosis, can be acute, subacute or chronic. Cutaneous, osteoarticular, genitourinary or central nervous system involvement may result from extra-pulmonary dissemination. The Infectious Diseases Society of America has published treatment guidelines for blastomycosis Chapman (Clin Infect Dis 46:1801-1812, 2008). Oral itraconazole has been the mainstay of therapy for mild to moderate infection, while amphotericin B, or alternatively a lipid formulation, is reserved for more severe infection. Newer triazoles, such as voriconazole and posaconazole, have shown clinical potential and expand available treatment options.
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Cleary JH. A case of generalized blastomycosis. Cook County Hospital Reports. 1904: 293-299.
Sarosi GA, Davies SF. Blastomycosis: state of the art. Am Rev Respir Dis. 1979;120:911–38.
Chu JH, Feudtner C, Heydon K, Walsh TJ, Zaoutis TE. Hospitalizations for endemic mycoses: a population-based national study. Clin Infect Dis. 2006;42:822–5.
Crampton TL, Light RB, Berg GM, et al. Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals. Clin Infect Dis. 2002;34:1310–6.
Meyer KC, McManus EJ, Maki DG. Overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome. New Engl J Med. 1993: 1231-1236.
Vasquez JE, Mehta JB, Agrawal R, Sarubbi FA. Blastomycosis in northeast Tennessee. Chest. 1998;114:436–43.
• Reed KD, Meece JK, Archer JR, Peterson AT. Ecologic niche modeling of Blastomyces dermatitidis in Wisconsin. PLOS One. 2008; 3: e2034. A fascinating look at the epidemiology of blastomycosis, including the effects of geography and climate, by experts in this field.
Klein BS, Vergeront JM, Weeks RJ, et al. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin. New Engl J Med. 1986;314:529–34.
Pfister JR, Archer JR, Hersil S, et al. Non-rural point source outbreak near a yard waste collection site. Clin Med Res. 2011;9:57–65.
Dworkin MS, Duckro AN, Proia L, Semel JD, Huhn G. The epidemiology of blastomycosis in Illinois and factors associated with death. Clin Infect Dis. 2005;41(12):e107–11.
Hussein R, Khan S, Levy F, Mehta JB, Sarubbi FA. Blastomycosis in the mountainous region of northeast Tennessee. Chest. 2009;135:1019–23.
Graham Carlos W, Rose AS, Wheat LJ, et al. Blastomycosis in Indiana: digging up more cases. Chest. 2010;138:1377–82.
Farber ER, Leahy MS, Meadows TR. Endometrial blastomycosis acquired by sexual contact. Obstet Gynecol. 1968;32:1950199.
Kralt D, Light B, Cheang M, et al. Clinical characteristics and outcomes in patients with pulmonary blastomycosis. Mycopathologia. 2009;167:115–24.
Witorsch P, Utz JP. North American blastomycosis: a study of 40 patients. Medicine. 1968;47:169–200.
Chapman SW, Lin AC, Hendricks KA, et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect. 1997;12:219–28.
Cherniss EI, Waisbren BA. North American blastomycosis: a clinical study of 40 cases. Ann Intern Med. 1956;44:105–23.
Kaplan W, Clifford MK. Blastomycosis: a review of 198 collected cases in veterans administration hospitals. Am Rev Respir Dis. 1964;89:659–72.
Pappas PG, Pottage JC, Powderly WG, et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Annals Intern Med. 1992;116(10):847–53.
Pappas PG, Threlkeld MG, Bedsole GD, et al. Blastomycosis in immunocompromised patients. Medicine. 1993;72(5):311–25.
Grim SA, Proia LA, Miller R, et al. A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation. Transpl Infect Dis. 2012;14:17–23.
McCann DA, Smith HL. Infliximab associated Blastomyces dermatitidis in treatment of ulcerative colitis. Colorectal Dis. 2012, In press.
Gruszka S. Associations of genetic variation and clinical characteristics of Blastomyces dermatitidis infections in Wisconsin. 2010. Accessed at http://www.minds.wisconsin.edu
• Bariola J, Perry P, Pappas P et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010; 50: 797-804. The most comprehensive review of CNS blastomycosis to date.
Bradsher RW, Chapman SW, Pappas PG. Blastomycosis. Infect Dis Clin N Am. 2003;17:21–40.
Harris JR, Blaney DD, Lindsley MD, et al. Blastomycosis in man after kinkajou bite. Emerg Infect Dis. 2011;17:268–70.
Lin MY, Chihara S, Smith KY, et al. Classic pyomyositis of the extremities as an unusual manifestation of Blastomyces dermatitidis: a report of two cases. Mycoses. 2010;53:356–9.
Inoshita T, Youngberg GA, Boelen LJ, Langston J. Blastomycosis presenting with prostatic involvement: report of 2 cases and review of the literature. J Urol. 1983;130:160–2.
Murray JJ, Clark CA, Lands RH. Reactivation blastomycosis presenting as a tubo-ovarian abscess. Obstet Gynecol. 1984;64:828–30.
Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23:367–81.
Merz WG, Roberts GD. Algorithms for detection and identification of fungi. In Manual of Clinical Microbiology. Edited by Murray PR. Washington, DC: ASM Press; 1999; 1167-1183.
Vyas KS, Bariola JR, Bradsher RW. Advances in the serodiagnosis of blastomycosis. Curr Fung Infect Rep. 2008;2:227–31.
Durkin M, Witt J, LeMonte A, et al. Antigen assay with the potential to aid in diagnosis of blastomycosis. J Clin Microbiol. 2004;42:4873–5.
Connolly P, Hage CH, Bariola JR, et al. Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay. Clin Vaccine Immunol. 2011;19:53–6.
Wheat J, Wheat H, Connolly P, et al. Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses. Clin Infect Dis. 1997;24:1169–71.
Sidamonidze K, Peck MK, Perez M, et al. Real-time PCR assay for identification of Blastomyces dermatitidis in culture and in tissue. J Clin Microbiol. 2012;50:1783–6.
• 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; 46:1801-1812. This is an essential read for clinicians who manage blastomycosis and if only one article can be read, it should be this one. It provides a comprehensive overview of the treatment of blastomycosis.
Recht LD, Philips JR, Eckman MR, Sarosi GA. Self-limited blastomycosis: a report of thirteen cases. Am Rev Respir Dis. 1979;120:1109–12.
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27–72.
Dismukes WE, Bradsher RW, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. Am J Med. 1992;93:489–97.
Itraconazole package insert. In: Ortho-McNeil-Janssen Pharmaceuticals, April 2008.
Barone JA, Koh JG, Bierman RH, et al. Food interaction and steady state pharmacokinetics of itraconazole capsules in healthy male volunteers. Antimicrob Agents Chemother. 1993;37:778–84.
Stein AG, Daneshmend TK, Warnock DW, et al. The effects of H2-receptor antagonists on the pharmacokinetics of itraconazole, a new oral antifungal. Br J Clin Pharmacol. 1989;27:105–6.
Jaruratanasirikul S, Sriviriyajan S. Effect of omeprazole on the pharmacokinetics of itraconazole. Eur J Clin Pharmacol. 1998;54:159–61.
Barone JA, Moskovitz BL, Gaurnieri J, et al. Enhanced bioavailability of itraconazole in hydroxypropyl-ß-cyclodextrin solution versus capsules in healthy volunteers. Antimicrob Agnets Chemother. 1998;42:1862–5.
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;44:1734–6.
Poirier M, Cheymol G. Optimisation of itraconazole therapy using target drug concentrations. Clin Pharmacokinet. 1998;35:461–73.
Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother. 2009;53:24–34.
Lestner JM, Roberts SA, Moore CB, et al. Toxicodynamics of Itraconazole: implications for therapeutic drug monitoring. Clin Infect Dis. 2009;49:928–30.
Saad AH, DePestel DD, Carver PL. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants. Pharmacotherapy. 2006;26:1730–44.
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;182:274–82.
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;37:728–32.
Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal. Clin Infect Dis. 2003;36:630–7.
Sugar AM, Liu XP. Efficacy of voriconazole in treatment of murine pulmonary blastomycosis. Antimicrob Agents Chemother 2001; 601-604.
Freifeld A, Proia L, Andes D, et al. Voriconazole use for endemic fungal infections. Antimicrob Agents Chemother. 2009;53:1648–51.
Ta M, Flowers SA, Rogers PD. The role of voriconazole in the treatment of central nervous system blastomycosis. Ann Pharmacother. 2009;43:1696–700.
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;20:267–71.
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;36:2950–6.
Sugar AM, Liu XP. In vitro and in vivo activities of SCH56592 against Blastomyces dermatitidis. Antimicrob Agents Chemother. 1996;40:1314–6.
Pascual A, Calandra T, Bolay S. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008;46:201–11.
• Smith J, Safdar N, Knasinski V et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006; 50: 1570-1572. Any clinician who prescribes voriconazole will benefit from understanding its complicated pharmacokinetics and the necessity of TDM.
Krishna G, Ma L, Martinho M, O’Mara E. Single-dose phase I study to evaluate the pharmacokinetics of posaconazole in new tablet and capsule formulations relative to oral suspension. Antimicrob Agents Chemother. 2012;56:4196–201.
Nagappan V, Deresinski S. Posaconazole: a broad spectrum triazole antifungal agent. Clin Infect Dis. 2007;45:1610–7.
Krishna G, Moton A, Ma L, Medlock MM, McLeod J. Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother. 2009;53:958–66.
Proia LA, Harnisch DO. Successful use of posaconazole for treatment of blastomycosis. Antimicrob Agents Chemother. 2012;56:4029.
Thompson GR, Wiederhold NP. Isavuconazole: a comprehensive review of spectrum of activity of a new triazole. Mycopathologia. 2010;170:291–313.
• Smith JA, Kauffman CA. Endemic fungal infections in patients receiving tumor necrosis factor-α inhibitor therapy. Drugs. 2009; 69: 1403-1415. A well-written overview of endemic mycoses associated with TNF antagonists and recommendations for management.
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Proia, L.A. How I Treat Blastomycosis. Curr Fungal Infect Rep 7, 21–28 (2013). https://doi.org/10.1007/s12281-012-0121-y
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DOI: https://doi.org/10.1007/s12281-012-0121-y