Treatment recommendations for histoplasmosis are summarized in Table 111-1. Treatment is indicated for all patients with PDH or chronic pulmonary histoplasmosis as well as for symptomatic patients with acute pulmonary histoplasmosis causing diffuse infiltrates, especially with hypoxemia. In most cases of pulmonary histoplasmosis, treatment is not recommended because the degree of exposure is not heavy; the infection is asymptomatic or symptoms are mild, subacute, and not progressive; and the illness resolves without therapy.
The preferred treatments for histoplasmosis include the lipid formulations of amphotericin B (AmB) in more severe cases and itraconazole in others. Liposomal AmB has been more effective than the deoxycholate formulation for treatment of PDH in patients with AIDS. The deoxycholate formulation is an alternative to lipid formulations for patients at low risk for nephrotoxicity. Posaconazole, voriconazole, and fluconazole are alternatives for patients who cannot take itraconazole.
In severe cases requiring hospitalization, a lipid formulation of AmB is followed by itraconazole. In patients with meningitis, a lipid formulation of AmB should be given for 4–6 weeks before the switch to itraconazole. In immunosuppressed patients, the degree of immunosuppression should be reduced if possible, although immune reconstitution inflammatory syndrome (IRIS) may ensue. Antiretroviral treatment improves the outcome of PDH in patients with AIDS and is recommended; however, whether antiretroviral treatment should be delayed to avoid IRIS is unknown.
Blood levels of itraconazole should be monitored to ensure adequate drug exposure, with target concentrations of the parent drug and its hydroxy metabolites of 1–5 μg/mL as measured by high-performance liquid chromatography and 2–10 μg/mL as measured by microbiologic assay. Drug interactions should be carefully assessed: itraconazole not only is cleared by cytochrome P450 metabolism but also inhibits cytochrome P450. This profile causes interactions with many other medications.
The duration of treatment for acute pulmonary histoplasmosis is 6–12 weeks, while that for PDH and chronic pulmonary histoplasmosis is ≥1 year. Antigen levels in urine and serum should be monitored during and for at least 1 year after therapy for PDH. Stable or rising antigen levels suggest treatment failure or relapse.
Previously, lifelong itraconazole maintenance therapy was recommended for patients with AIDS once histoplasmosis was diagnosed. Today, however, maintenance therapy is not required for patients who respond well to antiretroviral therapy, with CD4+ T cell counts of at least 150/μL (preferably >250/μL); who complete at least 1 year of itraconazole therapy; and who exhibit neither clinical evidence of active histoplasmosis nor an antigenuria level of >4 ng/mL. Maintenance therapy also appears to be unnecessary in patients receiving immunosuppressive treatment if the degree of immunosuppression can be reduced through an approach similar to that used for patients with AIDS.
Fibrosing mediastinitis, which represents a chronic fibrotic reaction to past mediastinal histoplasmosis rather than an active infection, does not respond to antifungal therapy. While treatment is often prescribed for patients with pulmonary histoplasmosis who have not recovered within 1 month and for those with persistent mediastinal lymphadenopathy, the effectiveness of antifungal therapy in these situations is unknown.