Paracoccidioidomycosis Treatment & Management

Updated: Apr 04, 2018
  • Author: Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH; Chief Editor: Michael Stuart Bronze, MD  more...
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Treatment

Approach Considerations

Systemic antifungal medications are the mainstay of medical management in paracoccidioidomycosis. Supportive measures and hospitalization may be warranted for patients with severe disease. If present, anemia and nutritional deficiencies should be treated.

Pregnancy

Paracoccidioidomycosis is uncommon in women of childbearing age. In one case of paracoccidioidomycosis in pregnancy, P brasiliensis was found in the placenta, but the child was not infected.

Amphotericin B is the only antifungal medication in pregnancy category B that is effective against P brasiliensis. All of the other medications that are currently used are category C or D.

Patients with HIV/AIDS

Patients with AIDS acquire a form of paracoccidioidomycosis that resembles the subacute juvenile type. Widespread disease quickly develops, and the meninges are more commonly involved in patients with AIDS than in patients who do not have AIDS.

Paracoccidioidomycosis is an AIDS-associated opportunistic infection. However, the incidence is lower than that expected by comparison to other endemic fungal infections. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) for Pneumocystis jiroveci pneumonia prophylaxis and azoles (eg, fluconazole, itraconazole, ketoconazole) for oropharyngeal candidiasis prophylaxis in HIV-infected patients may aid in the reduction in disseminated paracoccidioidomycosis.

AIDS is seen primarily in urban areas, whereas paracoccidioidomycosis is found mainly in rural areas, possibly contributing to the fact that the rate of paracoccidioidomycosis occurrence is lower than expected.

The paracoccidioidin skin test is frequently negative in infected patients with AIDS.

Supportive care

Supportive care among patients with paracoccidioidomycosis includes the following:

  • Treatment of anemia

  • Improvement of diet

  • Ensuring patient rest

  • Advising the patient to stop smoking and consuming alcohol

Surgery

Occasionally, specific surgical treatments are warranted for life- or organ-threatening disease, such as neurosurgical procedures to relieve granuloma-induced spinal cord compression or hydrocephalus. Reconstructive surgery is sometimes needed to alleviate fibrotic sequelae.

Deterrence/prevention

No vaccine against Paracoccidioides has been developed, although several peptide vaccines have been studied. No known control measures prevent paracoccidioidomycosis.

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Antifungal Treatment

Triazoles (itraconazole, voriconazole, posaconazole)

Itraconazole is considered the drug of choice for paracoccidioidomycosis, with a reported effectiveness of 95%. The course of therapy is typically 200 mg/day for 6 months. Itraconazole is considered superior to ketoconazole because of shorter treatment course, lower toxicity profile, and lower relapse rate (3-5%). Fluconazole is not typically used, because of its lower response rates and more frequent relapse.

Voriconazole, a newer azole agent, has in vitro activity against the yeast cells of P brasiliensis and has been shown in open-label trials to be an effective agent. [31] Another newer azole, posaconazole, has been used with reported success in this disease.

Imidazoles (ketoconazole)

Ketoconazole is also an effective agent for paracoccidioidomycosis, with a cure rate of 85-90% and an associated relapse rate of less than 10%. A dose of 200-400 mg/day in adults or 5 mg/kg/day in children for 6-18 months is required. Ketoconazole is associated with significant toxicities, including hepatic dysfunction and sex hormone alterations, as well as with many drug-drug interactions.

Sulfonamides (sulfadiazine, trimethoprim-sulfamethoxazole)

The maximum dose of sulfadiazine is 4 g/day in adults and 60-100 mg/kg/day in divided doses in children. Once clinical and mycologic response is evident, this dose can be cut in half. For long-acting compounds, the dosing is 0.5 g/day, following an initial dose of 1 g/day for 2-3 weeks. Patients should be treated for 3-5 years. This results in a 70% cure rate, but there is also a 30% relapse rate.

Trimethoprim-sulfamethoxazole (TMP-SMX) is typically dosed as one double-strength tablet (160 mg trimethoprim, 800 mg sulfamethoxazole) twice daily (8-10 mg/kg/day [based on trimethoprim] for children). Compared to itraconazole in a recent study, TMP-SMX treatment was associated with a 51% cure rate (versus 86% for itraconazole) with a median treatment time of 23 months (versus 12 months for itraconazole). [32]

Amphotericin B

Reserve this drug for severe cases of paracoccidioidomycosis that are refractory to other forms of therapy. Cumulative doses range from 1-2 g based on clinical response. The drug is not curative; therefore, maintenance therapy with a sulfonamide or an azole is subsequently required. Only the intravenous formulation of this drug is effective, but its use is limited because of associated toxicities. The associated rate of improvement and relapse rate are similar to those of sulfonamide.

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Consultations

Consult an infectious disease specialist for difficult diagnoses, especially in nonendemic areas, and for patients who require long-term treatment with potentially toxic medications (eg, amphotericin B).

Consider the following consultations as well, depending on organ involvement and severity of disease:

  • Pulmonologist

  • Internal medicine specialist

  • Dermatologist

  • Surgeon

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Long-Term Monitoring

During and after treatment for paracoccidioidomycosis with antifungal medications, patients must be regularly evaluated to ensure an adequate response to therapy and monitor for relapse.

Complement fixation tests can be used to track the response to therapy; antibody levels decrease with improvement. Complement fixation also can be used to detect relapse because antibody levels increase again. The new antibody tests directed against P brasiliensis antigenic glycoproteins may prove useful in monitoring disease activity and response to therapy.

Absence of symptoms for 2 years after antifungal therapy is considered by some to indicate a cure. Others believe that mycologically negative results in 3 specimens after the cessation of therapy indicate a cure.

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