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• Histoplasmosis Return to Top

• 1. Adult treatment:

• 1.1 Pulmonary

• 1.1.1 Acute pulmonary histoplasmosis

• 1.1.1.1 Moderate severe or severe

• Preferred regimen (1): Lipid formulation of Amphotericin B (3.0–5.0 mg/kg IV q12h for 1–2 weeks) THEN Itraconazole (200 mg tid for 3 days THEN 200 mg bid for a total of 12 weeks).
• Alternative regimen (2): The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg q24h IV) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity (A-III)
• Preferred regimen (3): Methylprednisolone (0.5–1.0 mg/kg daily intravenously) during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress (B-III).
• Note (1): In severe cases, cases accompanied by respiratory insufficiency, or hypoxemia, anecdotal reports [49] suggest that corticosteroid therapy may hasten recovery
• Note (2): The pulmonary infiltrates should be resolved on the chest radiograph before antifungal therapy is stopped.

• 1.1.1.2 Mild to moderate:

• Treatment is usually unnecessary
• Patients who continue to have symptoms for >1 month: Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks)
• Note (1): Antifungal treatment is unnecessary in patients with mild symptoms caused by acute pulmonary histoplasmosis

• 1.1.2 Chronic cavitary pulmonary histoplasmosis:

• Preferred regimen: Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for at least 1 year) is recommended
• Note (1): Blood levels of itraconazole should be obtained after the patient has been receiving this agent for at least 2 weeks to ensure adequate drug exposure
• Note (2): Patients with underlying emphysema often develop progressive pulmonary disease, which is characterized by cavities with surrounding inflammation, after infection with Hysotplasma capsulatum

• 1.1.3 Broncholithiasis

• Antifungal treatment is not recommended **
• Note: Bronchoscopic or surgical removal of the broncholith is recommended

• 1.1.4 Pulmonary nodules

• Antifungal treatment is not recommended**
• Note: Lung parenchymal sites of infection may contract and then persist indefinitely as lung nodules or histoplasmomas.... (what about this large comment)

• 1.2 Mediastinitis (alphabetic order?)

• 1.2.1 Mediastinal lymphadenitis
• Treatment is usually unnecessary (if asympthomatic)**

• 1.2.1.1Patients who have symptoms that warrant treatment with corticosteroids and in those who continue to have symptoms for >1 month

• Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks)

• 1.2.1.2 Severe cases with obstruction or compression of contiguous structures

• Preferred regimen: Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks)
• Note (1): Antifungal treatment is unnecessary in most patients with symptoms due to mediastinal lymphadenitis
• Note (2): Itraconazole is recommended for 6–12 weeks to reduce the risk of progressive disseminated disease caused by corticosteroid-induced immunosuppression in patients who are given corticosteroids and in patients whose symptoms last longer than 1 month.

• 1.2.2 Mediastinal Granuloma
• Treatment is usually unnecessary **
• 1.2.2.1 Symptomatic cases
• Preferred regimen: Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks)

• Note: Itraconazole is appropriate for symptomatic cases, but there are no controlled trials to prove its efficacy.
• Note (2): There is no evidence that mediastinal granuloma evolves into mediastinal fibrosis. Thus, treatment with either surgery or itraconazole should not be used to prevent the development of mediastinal fibrosis

• 1.2.3 Mediastinal Fibrosis
• Antifungal treatment is not recommended**
• 1.2.3.1 If clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma No differentiate from mediastinal fibrosis and granuloma ***
• Preferred regimen: Itraconazole (200 mg once or twice daily for 12 weeks)

• Note: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
• Note (2): Mediastinal fibrosis is characterized by invasive fibrosis that encases mediastinal or hilar nodes and that is defined by occlusion of central vessels and airways

• 1.3 Pericarditis:

• 1.3.1 Mild cases

• Preferred regimen: Nonsteroidal anti-inflammatory therapy

• 1.3.2 Patients with evidence of hemodynamic compromise or unremitting symptoms after several days of therapy with nonsteroidal anti-inflammatory therapy

• Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks)

• 1.3.3 If corticosteroids are administered

• Preferred regimen: Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks)
• Note (1): Pericardial fluid removal is indicated for patients with hemodynamic compromise
• Note (2): Pericarditis occurs as a complication of inflammation in adjacent mediastinal lymph nodes in patients with acute pulmonary histoplasmosis.

• 1.4 Central nervous system histoplasmosis

• Preferred regimen: Liposomal amphotericin B (5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks) followed by itraconazole (200 mg 2 or 3 times daily) for at least 1 year and until resolution of CSF abnormalities, including Histoplasma antigen levels.
• Note: Blood levels of itraconazole should be obtained to ensure adequate drug exposure

• 1.5 Rheumatologic syndromes

• 1.5.1 Mild cases

• Preferred regimen: Nonsteroidal anti-inflammatory therapy

• 1.5.2 Severe cases

• Preferred regimen: Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks)

• 1.5.3 Corticosteroids administration

• Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks)
• Note (1): If corticosteroids are used, concurrent itraconazole treatment is recommended to reduce the risk of progressive infection
• Note (2): Bone or joint involvement is very rare in progressive disseminated histoplasmosis, but it should not be overlooked.

• 1.6 Progressive disseminated histoplasmosis

• 1.6.1 Moderately severe to severe disease

• Preferred regimen: Liposomal amphotericin B (3.0 mg/kg daily) is recommended for 1–2 weeks, followed by oral itraconazole (200 mg 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months)
• Note (1): Substitution of another lipid formulation at a dosage of 5.0 mg/kg daily may be preferred in some patients because of cost or tolerability
• Note (2): The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity

• 1.6.2 Immunosupressed patients

• Lifelong suppressive therapy with itraconazole (200 mg daily)

• 1.6.3 Mild to moderate disease

• Itraconazole (200 mg 3 times daily for 3 days and then twice daily for at least 12 months)
• Note (1): Lifelong suppressive therapy with itraconazole (200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed and in patients who relapse despite receipt of appropriate therapy
• Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
• Note (3): Antigen levels should be measured during therapy and for 12 months after therapy is ended to monitor for relapse (B-III). Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.

• • • evidence summary...

• 14Performance Measures *** (This could be as a note) ***
• Preferred regimen: Itraconazole is the preferred azole for initial therapy for patients with mild-to-moderate histoplasmosis and as step-down therapy after receipt of amphotericin B
• Note: When other azole agents are used, the medical record should document the specific reasons that itraconazole was not used and why other azoles were used.
• 14.1 Severe or moderately severe histoplasmosis
• Preferred regimen: Amphotericin B.
• Note: When amphotericin B is used, the patient's electrolyte level, renal function, and blood cell count should be monitored several times per week and documented in the medical record.
• Note (2): Itraconazole drug levels should be measured during the first month in patients with disseminated or chronic pulmonary histoplasmosis, and these levels should be documented in the medical record, as well as the physician's response to levels that are too low.
• Note (3): Itraconazole should not be given to patients receiving contraindicated medications (i.e., pimozide, quinidine, dofetilide, lovastatin, simvastatin, midazolam, and triazolam). Reasons for deviation from this practice should be documented in the medical record.

• 1.7 Prophylaxis recommended for immunosuppressed patients

• Preferred regimen: Itraconazole (200 mg daily) in patients with HIV infection with CD4 cell counts <150 cells/mm3 in specific areas of endemicity where the incidence of histoplasmosis is >10 cases per 100 patient-years
• Note: Prophylaxis with itraconazole (200 mg daily) may be appropriate in specific circumstances in other immunosuppressed patients

• • • evidence summary...

• 11.Treatment for Central nervous system Histoplasmosis

• Preferred regimen: Liposomal amphotericin B (5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks) followed by itraconazole (200 mg 2 or 3 times daily) for at least 1 year and until resolution of CSF abnormalities, including Histoplasma antigen levels.
• Note: Blood levels of itraconazole should be obtained to ensure adequate drug exposure

• • • evidence summary...

• 12.Histoplasmosis in Pregnancy

• Preferred regimen: Lipid formulation amphotericin B (3.0–5.0 mg/kg daily for 4–6 weeks) is recommended
• Prefered regimen low risk for nephrotoxicity: The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily) is an alternative to a lipid formulation
• Note: If the newborn shows evidence for infection, treatment is recommended with amphotericin B deoxycholate (1.0 mg/kg daily for 4 weeks)
• Note (2): Unique issues in pregnancy include the risk of teratogenic complications of azole therapy [93] and of transplacental transmission of H. capsulatum to the fetus

• 13.Histoplasmosis in Children

• 13.1 Acute pulmonary histoplasmosis
• Note: Treatment indications and regimens are similar to those for adults, except that amphotericin B deoxycholate (1.0 mg/kg daily) is usually well tolerated, and the lipid preparations are not preferred
• Itraconazole dosage: 5.0–10.0 mg/kg daily in 2 divided doses (not to exceed 400 mg daily), generally using the solution formulation

• • • Evidence summary

• 14Performance Measures ***
• Preferred regimen: Itraconazole is the preferred azole for initial therapy for patients with mild-to-moderate histoplasmosis and as step-down therapy after receipt of amphotericin B
• Note: When other azole agents are used, the medical record should document the specific reasons that itraconazole was not used and why other azoles were used.
• 14.1 Severe or moderately severe histoplasmosis
• Preferred regimen: Amphotericin B.
• Note: When amphotericin B is used, the patient's electrolyte level, renal function, and blood cell count should be monitored several times per week and documented in the medical record.
• Note (2): Itraconazole drug levels should be measured during the first month in patients with disseminated or chronic pulmonary histoplasmosis, and these levels should be documented in the medical record, as well as the physician's response to levels that are too low.
• Note (3): Itraconazole should not be given to patients receiving contraindicated medications (i.e., pimozide, quinidine, dofetilide, lovastatin, simvastatin, midazolam, and triazolam). Reasons for deviation from this practice should be documented in the medical record.