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"Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America"

current
Published: Clinical Infectious Diseases ; 2007 ; 45 : 807 -825

Abstract

Every 12 to 18 months following publication, IDSA reviews its guidelines to determine whether an update is required. This guideline was last reviewed and deemed current as of 06/2011.

These updated guidelines replace the previous treatment guidelines published in 2000. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. Since 2000, several new antifungal agents have become available, and clinical trials and case series have increased our understanding of the management of histoplasmosis. Advances in immunosuppressive treatment for inflammatory disorders have created new questions about the approach to prevention and treatment of histoplasmosis.  

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Recommendations

 Treatment of Acute and Chronic Pulmonary Histoplasmosis

1. Lipid formulation of amphotericin B (3.0–5.0 mg/kg daily intravenously for 1–2 weeks) followed by itraconazole (200 mg 3 times daily for 3 days and then 200 mg twice daily, for a total of 12 weeks) is recommended (A-III).

2. The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily intravenously) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity (A-III).

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).

4. Treatment is usually unnecessary (A-III). Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks) is recommended for patients who continue to have symptoms for >1 month (B-III).

5. Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for at least 1 year) is recommended, but some prefer 18–24 months in view of the risk for relapse (A-II).

6. 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 (A-III).

Complications

7. Nonsteroidal anti-inflammatory therapy is recommended in mild cases (B-III).

8. Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks) is recommended for patients with evidence of hemodynamic compromise or unremitting symptoms after several days of therapy with nonsteroidal anti-inflammatory therapy (B-III).

9. Pericardial fluid removal is indicated for patients with hemodynamic compromise (A-III).

10. Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks) is recommended if corticosteroids are administered (B-III).

11. Nonsteroidal anti-inflammatory therapy is recommended in mild cases (B-III).

12. Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks) is recommended in severe cases (B-III).

13. Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks) is recommended only if corticosteroids are administered (B-III).

14. Treatment is usually unnecessary (A-III).

15. Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks) is recommended in patients who have symptoms that warrant treatment with corticosteroids and in those who continue to have symptoms for >1 month (B-III).

16. Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks) is recommended in severe cases with obstruction or compression of contiguous structures (B-III).

17. Treatment is usually unnecessary (A-III)

18. Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks) is recommended for symptomatic cases (B-III).

19. Antifungal treatment is not recommended (A-III).

20. The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction (B-III).

21. Itraconazole (200 mg once or twice daily for 12 weeks) is recommended if clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma (C-III).

22. Antifungal treatment is not recommended (A-III).

23. Bronchoscopic or surgical removal of the broncholith is recommended (A-III).

24. Antifungal treatment is not recommended (A-III).

Progressive Disseminated Histoplasmosis

25. For moderately severe to severe disease, 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) (A-I).

26. 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 (A-III).

27. 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 (A-III).

28. For mild-to-moderate disease, itraconazole (200 mg 3 times daily for 3 days and then twice daily for at least 12 months) is recommended (A-II).

29. Lifelong suppressive therapy with itraconazole (200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed (A-II) and in patients who relapse despite receipt of appropriate therapy (C-III).

30. Blood levels of itraconazole should be obtained to ensure adequate drug exposure (B-III).

31. 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.

Prophylaxis for Immunosuppressed Patients

32. Prophylaxis with itraconazole (200 mg daily) is recommended 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 (A-I).

33. Prophylaxis with itraconazole (200 mg daily) may be appropriate in specific circumstances in other immunosuppressed patients (C-III).

CNS Histoplasmosis

34. 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, is recommended (B-III).

35. Blood levels of itraconazole should be obtained to ensure adequate drug exposure (B-III).

Histoplasmosis in Pregnancy

36. Lipid formulation amphotericin B (3.0–5.0 mg/kg daily for 4–6 weeks) is recommended (A-III).

37. 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 (A-III).

38. If the newborn shows evidence for infection, treatment is recommended with amphotericin B deoxycholate (1.0 mg/kg daily for 4 weeks) (A-III).

Histoplasmosis in Children

39. 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 (A-III).

40. Itraconazole dosage in children is 5.0–10.0 mg/kg daily in 2 divided doses (not to exceed 400 mg daily), generally using the solution formulation (A-III).

41. Amphotericin B deoxycholate (1.0 mg/kg daily for 4–6 weeks) is recommended (A-III).

42. Amphotericin B deoxycholate (1.0 mg/kg daily for 2–4 weeks) followed by itraconazole (5.0–10.0 mg/kg daily in 2 divided doses) to complete 3 months of therapy is an alternative (A-III).

43. Longer therapy may be needed for patients with severe disease, immunosuppression, or primary immunodeficiency syndromes (A-III).

44. Lifelong suppressive therapy with itraconazole (5.0 mg/kg daily, up to 200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed (A-II) and in patients who experience relapse despite receipt of appropriate therapy (C-III).

45. Blood levels of itraconazole should be obtained to ensure adequate drug exposure (B-III).

46. Antigen levels should be monitored 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.

 

Additional Resources

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