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Paracoccidioidomycosis Medication

  • Author: Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
 
Updated: Mar 23, 2015
 

Medication Summary

Antifungal medications are the mainstay of treatment for paracoccidioidomycosis. These include the following:

  • Itraconazole - The drug of choice [27, 29]
  • Ketoconazole
  • Fluconazole - Not as effective as either itraconazole or ketoconazole; its main advantages are that it is available in oral and intravenous forms and that it penetrates into the CSF well
  • Amphotericin B - Used in patients with severe disease; it is the only medication in this list in pregnancy category B; all of the other medications are in pregnancy category C or D.
  • Trimethoprim-sulfamethoxazole (TMP-SMZ) – Continues to be used because of low cost
  • Sulfadiazine - Also still used because of its low cost

Historically, the sulfonamides have been the most widely used medications for the treatment of paracoccidioidomycosis; their advantage is their low cost. However, relapses are more common with the sulfonamides than with other mediations, and longer courses of therapy may be required.

Reports have documented successful treatment of paracoccidioidomycosis with voriconazole, posaconazole, and terbinafine.[30] The following guidelines may be helpful: Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America.

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Antifungal agents

Class Summary

The mechanism of action may involve an alteration of RNA or DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Itraconazole (Sporanox, Onmel)

 

Itraconazole, a triazole antifungal agent, is preferred over the previously used agent ketoconazole because of reduced length of therapy and relapse rate. Adverse effects are also less frequent with itraconazole. This is a synthetic fungistatic triazole that inhibits cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

An intravenous formulation is available but no intravenous dose has been established for P brasiliensis treatment.

Ketoconazole

 

Imidazole is a broad-spectrum antifungal agent that inhibits the synthesis of ergosterol, a key fungal cell membrane component. This causes cellular components to leak, resulting in fungal cell death.

Amphotericin B, conventional

 

Amphotericin B is indicated for the treatment of life-threatening fungal infections or when oral antifungal medications cannot be tolerated. The drug is produced from a strain of Streptomyces nodosus. The antifungal activity of amphotericin B results from its ability to insert itself into the fungal cytoplasmic membrane at sites that contain ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium).

At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity. At higher concentrations, however, pores of 40-105 nm in are produced in the cytoplasmic membrane, leading to large losses of ions and other molecules.

A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Indeed, this may be the main fungicidal activity of amphotericin B.

Amphotericin B is not curative by itself; all patients treated with this drug require maintenance treatment with sulfonamide or an azole. Improvement occurs in 65-70% of patients treated with this agent.

Fluconazole (Diflucan)

 

Fluconazole has fungistatic activity. It is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents the conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. It is not considered the drug of choice in the treatment of paracoccidioidomycosis.

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Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Trimethoprim and sulfamethoxazole (Septra DS, Bactrim, Bactrim DS)

 

Sulfamethoxazole competes with para-aminobenzoic acid (PABA) and thereby inhibits microbial synthesis of dihydrofolate. Trimethoprim binds to and reversibly inhibits the enzyme dihydrofolate reductase, thereby blocking the production of tetrahydrofolic acid from dihydrofolic acid. Thus, 2 consecutive steps in the synthesis of essential nucleic acids and proteins are blocked. TMP-SMZ is used to treat paracoccidioidomycosis in Central and South America primarily because of its low cost, but it is not the drug of choice.

Sulfadiazine

 

Therapy with sulfa agents is long term (3-5 y) and is associated with a high relapse rate (20-25%). Paracoccidioidomycosis is the only mycosis amenable to treatment with sulfa drugs.

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Contributor Information and Disclosures
Author

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH Adjunct Professor of Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Infectious Diseases, International Society of Travel Medicine, Medical Mycological Society of the Americas, Armed Forces Infectious Diseases Society, International Society for Human and Animal Mycology, American College of Physicians, American Society for Microbiology, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Coauthor(s)

Kendall M Egan, MD, FAAD Dermatologist, Veteran's Affairs Medical Center; Dermatologist, Spruce Health, Dermatologist, DermOne

Kendall M Egan, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists

Disclosure: Nothing to disclose.

Chief Editor

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Asgar A Boxwalla, MD Staff Physician, Department of Internal Medicine, Division of Infectious Diseases, St John Detroit Riverview Hospital

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Department of Internal Medicine, Director of Infectious Disease Fellowship, Harper Hospital, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Julie E Dixon, MD, FAAD Private Practice, Ironwood Dermatology, Tucson, Arizona

Julie E Dixon, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Ronald A Greenfield, MD Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

Norman Levine, MD Private Practice, Tucson, AZ

Norman Levine is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Christina M Schofield, MD Instructor of Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Infectious Disease, Wilford Hall Medical Center, Lackland Air Force Base

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acknowledgments

The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Navy, Department of the Army, Department of Defense, or the U.S. Government.

References
  1. Marques-da-Silva SH, Rodrigues AM, de Hoog GS, Silveira-Gomes F, Camargo ZP. Occurrence of Paracoccidioides lutzii in the Amazon region: description of two cases. Am J Trop Med Hyg. 2012 Oct. 87(4):710-4. [Medline]. [Full Text].

  2. Lupi O, Tyring SK, McGinnis MR. Tropical dermatology: fungal tropical diseases. J Am Acad Dermatol. 2005 Dec. 53(6):931-51, quiz 952-4. [Medline].

  3. Brazão-Silva MT, Andrade MF, Franco T, Ribeiro RI, Silva Wdos S, Faria G, et al. Paracoccidioidomycosis: a series of 66 patients with oral lesions from an endemic area. Mycoses. 2011 Jul. 54(4):e189-95. [Medline].

  4. Bagagli E, Sano A, Coelho KI, Alquati S, Miyaji M, de Camargo ZP, et al. Isolation of Paracoccidioides brasiliensis from armadillos (Dasypus noveminctus) captured in an endemic area of paracoccidioidomycosis. Am J Trop Med Hyg. 1998 Apr. 58(4):505-12. [Medline].

  5. de Farias MR, Condas LA, Ribeiro MG, Bosco Sde M, Muro MD, Werner J, et al. Paracoccidioidomycosis in a dog: case report of generalized lymphadenomegaly. Mycopathologia. 2011 Aug. 172(2):147-52. [Medline].

  6. Trejo-Chávez A, Ramírez-Romero R, Ancer-Rodríguez J, Nevárez-Garza AM, Rodríguez-Tovar LE. Disseminated paracoccidioidomycosis in a Southern two-toed sloth (Choloepus didactylus). J Comp Pathol. 2011 Feb-Apr. 144(2-3):231-4. [Medline].

  7. Benard G, Kavakama J, Mendes-Giannini MJ, Kono A, Duarte AJ, Shikanai-Yasuda MA. Contribution to the natural history of paracoccidioidomycosis: identification of the primary pulmonary infection in the severe acute form of the disease--a case report. Clin Infect Dis. 2005 Jan 1. 40(1):e1-4. [Medline].

  8. Bellissimo-Rodrigues F, Bollela VR, Da Fonseca BA, Martinez R. Endemic paracoccidioidomycosis: relationship between clinical presentation and patients' demographic features. Med Mycol. 2013 Apr. 51(3):313-8. [Medline].

  9. Paniago AM, de Freitas AC, Aguiar ES, Aguiar JI, da Cunha RV, Castro AR, et al. Paracoccidioidomycosis in patients with human immunodeficiency virus: review of 12 cases observed in an endemic region in Brazil. J Infect. 2005 Oct. 51(3):248-52. [Medline].

  10. Corti M, Villafañe MF, Negroni R, Palmieri O. Disseminated paracoccidioidomycosis with peripleuritis in an AIDS patient. Rev Inst Med Trop Sao Paulo. 2004 Jan-Feb. 46(1):47-50. [Medline].

  11. Azenha MR, Caliento R, Brentegani LG, de Lacerda SA. A retrospective study of oral manifestations in patients with paracoccidioidomycosis. Braz Dent J. 2012. 23(6):753-7. [Medline].

  12. Mayr A, Kirchmair M, Rainer J, Rossi R, Kreczy A, Tintelnot K, et al. Chronic paracoccidioidomycosis in a female patient in Austria. Eur J Clin Microbiol Infect Dis. 2004 Dec. 23(12):916-9. [Medline].

  13. Blotta MH, Mamoni RL, Oliveira SJ, Nouér SA, Papaiordanou PM, Goveia A, et al. Endemic regions of paracoccidioidomycosis in Brazil: a clinical and epidemiologic study of 584 cases in the southeast region. Am J Trop Med Hyg. 1999 Sep. 61(3):390-4. [Medline].

  14. Maluf ML, Pereira SR, Takahachi G, Svidzinski TI. [Prevalence of paracoccidioidomycosis infection determined by sorologic test in donors' blood in the Northwest of Paraná, Brazil]. Rev Soc Bras Med Trop. 2003 Jan-Feb. 36(1):11-6. [Medline].

  15. Cabral-Marques O, Schimke LF, Pereira PV, Falcai A, de Oliveira JB, Hackett MJ, et al. Expanding the clinical and genetic spectrum of human CD40L deficiency: the occurrence of paracoccidioidomycosis and other unusual infections in Brazilian patients. J Clin Immunol. 2012 Apr. 32(2):212-20. [Medline].

  16. Nogueira LM, Santos M, Ferreira LC, Talhari C, Rodrigues RR, Talhari S. AIDS-associated paracoccidioidomycosis in a patient with a CD4+ T-cell count of 4 cells/mm³. An Bras Dermatol. 2011 Jul-Aug. 86(4 Suppl 1):S129-32. [Medline].

  17. Desjardins CA, Champion MD, Holder JW, Muszewska A, Goldberg J, Bailão AM, et al. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis. PLoS Genet. 2011 Oct. 7(10):e1002345. [Medline]. [Full Text].

  18. Shankar J, Restrepo A, Clemons KV, Stevens DA. Hormones and the resistance of women to paracoccidioidomycosis. Clin Microbiol Rev. 2011 Apr. 24(2):296-313. [Medline]. [Full Text].

  19. Coutinho ZF, Silva Dd, Lazera M, Petri V, Oliveira RM, Sabroza PC, et al. Paracoccidioidomycosis mortality in Brazil (1980-1995). Cad Saude Publica. 2002 Sep-Oct. 18(5):1441-54. [Medline].

  20. Pereira RM, Tresoldi AT, da Silva MT, Bucaretchi F. Fatal disseminated paracoccidioidomycosis in a two-year-old child. Rev Inst Med Trop Sao Paulo. 2004 Jan-Feb. 46(1):37-9. [Medline].

  21. de Almeida SM, Queiroz-Telles F, Teive HA, Ribeiro CE, Werneck LC. Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings. J Infect. 2004 Feb. 48(2):193-8. [Medline].

  22. Moreto TC, Marques ME, de Oliveira ML, Moris DV, de Carvalho LR, Mendes RP. Accuracy of routine diagnostic tests used in paracoccidioidomycosis patients at a university hospital. Trans R Soc Trop Med Hyg. 2011 Aug. 105(8):473-8. [Medline].

  23. Hahn RC, Rodrigues AM, Fontes CJ, Nery AF, Tadano T, Queiroz Lde P Jr. Fatal fungemia due to Paracoccidioides lutzii. Am J Trop Med Hyg. 2014 Aug. 91(2):394-8. [Medline].

  24. Kalmar EM, Alencar FE, Alves FP, et al. Paracoccidioidomycosis: an epidemiologic survey in a pediatric population from the Brazilian Amazon using skin tests. Am J Trop Med Hyg. 2004 Jul. 71(1):82-6. [Medline].

  25. Freitas RM, Prado R, Prado FL, Paula IB, Figueiredo MT, Ferreira CS, et al. Pulmonary paracoccidioidomycosis: radiology and clinical-epidemiological evaluation. Rev Soc Bras Med Trop. 2010 Nov-Dec. 43(6):651-6. [Medline].

  26. Reis F, Collier PP, Souza TF, Lopes GP, Bronzatto E, Silva Junior NA, et al. Neuroparacoccidioidomycosis (NPCM): magnetic resonance imaging (MRI) findings. Mycopathologia. 2013 Feb. 175(1-2):181-6. [Medline].

  27. Queiroz-Telles F, Goldani LZ, Schlamm HT, Goodrich JM, Espinel-Ingroff A, Shikanai-Yasuda MA. An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis. Clin Infect Dis. 2007 Dec 1. 45(11):1462-9. [Medline].

  28. Borges SR, Silva GM, Chambela Mda C, Oliveira Rde V, Costa RL, Wanke B, et al. Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200 patients with paracoccidioidomycosis. Med Mycol. 2014 Apr. 52(3):303-10. [Medline].

  29. Travassos LR, Taborda CP, Colombo AL. Treatment options for paracoccidioidomycosis and new strategies investigated. Expert Rev Anti Infect Ther. 2008 Apr. 6(2):251-62. [Medline].

  30. Ollague JM, de Zurita AM, Calero G. Paracoccidioidomycosis (South American blastomycosis) successfully treated with terbinafine: first case report. Br J Dermatol. 2000 Jul. 143(1):188-91. [Medline].

 
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Approximate distribution of paracoccidioidomycosis in North, Central, and South America, based on case reports.
Granulomatous lesion involving the nose in patient with paracoccidioidomycosis; note the resemblance to cutaneous leishmaniasis.
Potassium hydroxide (KOH) preparation from pus; note the multiple budding and variation in cell size with Paracoccidioides.
Crusted plaques over the central part of the face in a man with paracoccidioidomycosis. Courtesy of Rolando Vasquez, MD, Professor of Dermatology, Guatemala.
Ulcerated nodule on the tongue in a man with paracoccidioidomycosis. Courtesy of Heidi Logemann, Professor of Mycology, Universidad de San Carlos, Guatemala.
 
 
 
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