Currently, two main classes of antifungal agents are useful for the treatment of coccidioidomycosis (Table 112-1). While once prescribed routinely, amphotericin B in all its formulations is now reserved for only the most severe cases of dissemination and for intrathecal or intraventricular administration to patients with coccidioidal meningitis in whom triazole antifungal therapy has failed. The original formulation of amphotericin B, which is dispersed with deoxycholate, is usually administered intravenously in doses of 0.7–1.0 mg/kg either daily or three times per week. The newer lipid-based formulations—amphotericin B lipid complex (ABLC), amphotericin B colloidal dispersion (ABCD), and amphotericin B liposomal complex (L-AmB)—are associated with less renal toxicity. The lipid dispersions are administered intravenously at doses of 5 mg/kg daily or three times per week.
Triazole antifungals are the principal drugs now used to treat most cases of coccidioidomycosis. Clinical trials have demonstrated the usefulness of both fluconazole and itraconazole. Evidence indicates that itraconazole may be more efficacious against bone and joint disease. Because of its demonstrated penetration into CSF, fluconazole is the azole of choice for the treatment of coccidioidal meningitis, but itraconazole also is effective. For both drugs, a minimal oral adult dosage of 400 mg/d should be used. The maximal dose of itraconazole is 200 mg three times daily, but higher doses of fluconazole may be given. Two newer triazole antifungals, posaconazole and voriconazole, are now available. Data suggest that both drugs may be useful against infections, including meningitis, in which prior fluconazole therapy has failed. High-dose triazole therapy may be teratogenic during the first trimester of pregnancy; thus, amphotericin B should be considered as therapy for coccidioidomycosis in pregnant women during this period.
Most patients with focal primary pulmonary coccidioidomycosis require no therapy. Patients for whom antifungal therapy should be considered include those with underlying cellular immunodeficiencies and those with prolonged symptoms and signs of extensive disease. Specific criteria include symptoms persisting for ≥2 months, night sweats occurring for >3 weeks, weight loss of >10%, a serum CF antibody titer of >1:16, and extensive pulmonary involvement apparent on chest radiography.
Diffuse pulmonary coccidioidomycosis represents a special situation. Because most patients with this form of disease are profoundly hypoxemic and critically ill, many clinicians favor beginning therapy with amphotericin B and switching to an oral triazole antifungal once clinical improvement occurs.
The nodules that may follow primary pulmonary coccidioidomycosis do not require treatment. As noted above, these nodules are not easily distinguished from pulmonary malignancies by means of radiographic imaging. Close clinical follow-up and biopsy may be required to distinguish between these two entities. Most pulmonary cavities do not require therapy. Antifungal treatment should be considered in patients with persistent cough, pleuritic chest pain, and hemoptysis. Occasionally, pulmonary coccidioidal cavities become secondarily infected. This development is usually manifested by an air-fluid level within the cavity. Bacterial flora or Aspergillus species are commonly involved, and therapy directed at these organisms should be considered. Surgery is rarely required except in cases of persistent hemoptysis or pyopneumothorax. For chronic pulmonary coccidioidomycosis, prolonged antifungal therapy—lasting for at least 1 year—is usually required, with monitoring of symptoms, radiographic changes, sputum cultures, and serologic titers.
Most cases of disseminated coccidioidomycosis require prolonged antifungal therapy. Duration of treatment is based on resolution of the signs and symptoms of the lesions in conjunction with a significant decline in serum CF antibody titer. Such therapy routinely is continued for at least several years. Relapse occurs in 15–30% of individuals once therapy is discontinued.
Coccidioidal meningitis poses a special challenge. While most patients with this form of disease respond to treatment with oral triazoles, 80% experience relapse when therapy is stopped. Thus, lifelong therapy is recommended. In cases of triazole failure, intrathecal or intraventricular amphotericin B may be used. Installation requires considerable expertise and should be undertaken only by an experienced health care provider. Shunting of CSF in addition to appropriate antifungal therapy is required in cases of meningitis complicated by hydrocephalus. It is prudent to obtain expert consultation in all cases of coccidioidal meningitis.