Treatment of paracoccidioidomycosis
- Marcio Nucci, MD
Marcio Nucci, MD
- Associate Professor, Department of Internal Medicine Federal University of Rio de Janeiro
- Head, Mycology Laboratory
- Hospital Universitario Clementino Fraga Filho
- Arnaldo L Colombo, MD
Arnaldo L Colombo, MD
- Professor of Medicine, Division of Infectious Diseases
- Head, Special Mycology Laboratory
- Federal University of São Paulo
Paracoccidioidomycosis is a systemic endemic mycotic disease caused by the thermally dimorphic fungi of the genus Paracoccidioides. Two species are recognized to cause paracoccidioidomycosis: Paracoccidioides brasiliensis and Paracoccidioides lutzii. The fungus has a geographic distribution limited to Central and South America, and paracoccidioidomycosis is the most frequent systemic endemic mycosis in this region. Primary infection is usually transient and almost always devoid of clinical manifestations. If the infection is not contained by the host, the disease may evolve into one of two patterns: the chronic form, which represents reactivation of the primary infection and is most common, and the acute/subacute form .
The treatment of paracoccidioidomycosis will be reviewed here. The mycology, epidemiology, clinical manifestations and diagnosis of paracoccidioidomycosis are discussed separately. (See "Mycology and epidemiology of paracoccidioidomycosis" and "Clinical manifestations and diagnosis of acute/subacute paracoccidioidomycosis" and "Clinical manifestations and diagnosis of chronic paracoccidioidomycosis".)
Paracoccidioides spp are sensitive to most antifungal agents, including amphotericin B, the azoles (ketoconazole, fluconazole, itraconazole, voriconazole and posaconazole), terbinafine, and even sulfonamides . Of these agents, itraconazole has been studied most extensively and is used most commonly. Sulfonamides, such as trimethoprim-sulfamethoxazole, are used in some cases but require prolonged therapy to prevent relapse. Amphotericin B is reserved for patients with severe disease.
Despite the fact that paracoccidioidomycosis has a high incidence and morbidity in Central and South America, few studies have been conducted to define its optimal treatment. Only two randomized trials have been published, neither of which had sufficient power to assess response or cure rates [3,4].
Itraconazole — Itraconazole has been used extensively in the treatment of paracoccidioidomycosis and results in high response rates.
- Travassos LR, Taborda CP, Colombo AL. Treatment options for paracoccidioidomycosis and new strategies investigated. Expert Rev Anti Infect Ther 2008; 6:251.
- Menezes VM, Soares BG, Fontes CJ. Drugs for treating paracoccidioidomycosis. Cochrane Database Syst Rev 2006; :CD004967.
- Shikanai-Yasuda MA, Benard G, Higaki Y, et al. Randomized trial with itraconazole, ketoconazole and sulfadiazine in paracoccidioidomycosis. Med Mycol 2002; 40:411.
- Queiroz-Telles F, Goldani LZ, Schlamm HT, et al. An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis. Clin Infect Dis 2007; 45:1462.
- Naranjo MS, Trujillo M, Munera MI, et al. Treatment of paracoccidioidomycosis with itraconazole. J Med Vet Mycol 1990; 28:67.
- McGinnis MR, Pasarell L, Sutton DA, et al. In vitro evaluation of voriconazole against some clinically important fungi. Antimicrob Agents Chemother 1997; 41:1832.
- Barraviera B, Mendes RP, Machado JM, et al. Evaluation of treatment of paracoccidioidomycosis with cotrimazine (combination of sulfadiazine and trimetoprim). Preliminary report. Rev Inst Med Trop Sao Paulo 1989; 31:53.
- Queiroz-Telles, F, Colombo, AL, Nucci, M. Comparative efficacy of cotrimoxazole and itraconazole in the treatment of paracoccidioidomycosis. Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Diego) Washington, DC: American Society for Microbiology, 1998.
- Cavalcante Rde S, Sylvestre TF, Levorato AD, et al. Comparison between itraconazole and cotrimoxazole in the treatment of paracoccidiodomycosis. PLoS Negl Trop Dis 2014; 8:e2793.
- Borges SR, Silva GM, Chambela Mda C, et al. Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200 patients with paracoccidioidomycosis. Med Mycol 2014; 52:303.
- Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP, et al. [Guidelines in paracoccidioidomycosis]. Rev Soc Bras Med Trop 2006; 39:297.
- Dillon NL, Sampaio SA, Habermann MC, et al. Delayed results of treatment of paracoccidioidomycosis with amphotericin B plus sulfamides versus amphotericin B alone. Rev Inst Med Trop Sao Paulo 1986; 28:263.
- de Campos EP, Sartori JC, Hetch ML, de Franco MF. Clinical and serologic features of 47 patients with paracoccidioidomycosis treated by amphotericin B. Rev Inst Med Trop Sao Paulo 1984; 26:212.
- 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.
- Dietze R, Fowler VG Jr, Steiner TS, et al. Failure of amphotericin B colloidal dispersion in the treatment of paracoccidioidomycosis. Am J Trop Med Hyg 1999; 60:837.
- Martinez R, Malta MH, Verceze AV, Arantes MR. Comparative efficacy of fluconazole and amphotericin B in the parenteral treatment of experimental paracoccidioidomycosis in the rat. Mycopathologia 1999; 146:131.
- Hahn RC, Fontes CJ, Batista RD, Hamdan JS. In vitro comparison of activities of terbinafine and itraconazole against Paracoccidioides brasiliensis. J Clin Microbiol 2002; 40:2828.
- Quagliato Júnior R, Grangeia Tde A, Massucio RA, et al. Association between paracoccidioidomycosis and tuberculosis: reality and misdiagnosis. J Bras Pneumol 2007; 33:295.
- Vidal MS, Del Negro GM, Vicentini AP, et al. Serological diagnosis of paracoccidioidomycosis: high rate of inter-laboratorial variability among medical mycology reference centers. PLoS Negl Trop Dis 2014; 8:e3174.
- Del Negro GM, Pereira CN, Andrade HF, et al. Evaluation of tests for antibody response in the follow-up of patients with acute and chronic forms of paracoccidioidomycosis. J Med Microbiol 2000; 49:37.
- de Camargo ZP. Serology of paracoccidioidomycosis. Mycopathologia 2008; 165:289.
- Sylvestre TF, Franciscone Silva LR, Cavalcante Rde S, et al. Prevalence and serological diagnosis of relapse in paracoccidioidomycosis patients. PLoS Negl Trop Dis 2014; 8:e2834.
- Restrepo A, Tobon AM, Agudelo CA. Paracoccidioidomycosis. In: Diagnosis and Treatment of Human Mycoses, 1st edition, Hospenthal, DR, Rinaldi, MG (Eds), Humana Press, Totowa, NJ 2008. p.331.
- Tobón AM, Agudelo CA, Osorio ML, et al. Residual pulmonary abnormalities in adult patients with chronic paracoccidioidomycosis: prolonged follow-up after itraconazole therapy. Clin Infect Dis 2003; 37:898.
- Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: an update. Clin Microbiol Rev 1993; 6:89.
- Morejón KM, Machado AA, Martinez R. Paracoccidioidomycosis in patients infected with and not infected with human immunodeficiency virus: a case-control study. Am J Trop Med Hyg 2009; 80:359.
- Gryschek RC, Pereira RM, Kono A, et al. Paradoxical reaction to treatment in 2 patients with severe acute paracoccidioidomycosis: a previously unreported complication and its management with corticosteroids. Clin Infect Dis 2010; 50:e56.
- Pereira RM, Bucaretchi F, Barison Ede M, et al. Paracoccidioidomycosis in children: clinical presentation, follow-up and outcome. Rev Inst Med Trop Sao Paulo 2004; 46:127.
- ANTIFUNGAL AGENTS
- - Efficacy
- - Toxicity
- - Pharmacokinetics
- - Toxicity
- - Efficacy
- - Toxicity
- Amphotericin B
- - Efficacy
- - Toxicity
- Other drugs
- CHOICE OF THERAPY
- Mild to moderate
- Central nervous system involvement
- DURATION AND MONITORING
- Serologic testing
- Laboratory studies
- PARADOXICAL REACTIONS
- SUMMARY AND RECOMMENDATIONS