Management
Prophylaxis
Fluconazole and itraconazole have proven to be efficacious for prophylaxis of coccidioidomycosis in transplant recipients and both have been used for the prevention of donor-derived coccidioidomycosis (Table 5 and Table 6). Suggested regimens are fluconazole (400 mg daily) or itraconazole (200 mg twice daily). For patients already receiving itraconazole, voriconazole, or posaconazole for Aspergillus prophylaxis, additional fluconazole is not required. Transplant recipients whose antifungal prophylaxis consists of an echinocandin or inhaled aerosolized amphotericin B and who are at risk for donor-derived coccidioidomycosis should receive additional prophylaxis with an azole.
The optimal duration of prophylaxis for donor-derived coccidioidomycosis has not been determined. The lungs of an organ donor with active or previous coccidioidomycosis are likely to harbor organisms contained either in an area of inflammation or a granuloma. However, the precise risk of transmission from a previously infected donor via lung transplantation is not known. Since the organisms can remain viable within a granuloma, some centers employ lifelong prophylaxis in lung transplant recipients. Organs other than lungs may or may not harbor Coccidioides, and unless there is gross or histopathological evidence of such infection in the donor organ, the risk of donor-derived coccidioidomycosis is unknown. For recipients of nonlung organs from a donor with documented coccidioidomycosis, an option is to continue lifelong prophylaxis (perhaps with a fluconazole dose of 200 mg daily after the first posttransplant year). Alternatively, discontinuation of prophylaxis after 3–6 months with continued monitoring for clinical or serological evidence of coccidioidomycosis is also rational.
Treatment
The treatment of coccidioidomycosis has been summarized in published guidelines and is outlined in Table 7. Fluconazole (400–800 mg daily) and itraconazole (200 mg twice or thrice daily) are the antifungal agents of choice for the treatment of coccidioidomycosis. For patients with rapidly progressive or severe infection, a lipid formulation of amphotericin B is recommended at a dose of 5 mg/kg/day. Both voriconazole and posaconazole are active in vitro for Coccidioides and have been used as salvage therapy in transplant recipients. No standard recommendation for the duration of treatment exists as response to therapy may vary. Generally, the patient should be treated until the infection is quiescent based on clinical, serological and radiographic follow-up, and this may take months or years to achieve. Once control has been documented for at least 12 months, lifelong prophylaxis is recommended. Secondary prophylaxis most often employs a lower dose of the same azole used to treat the infection. Optimal regimens should include fluconazole dosed no less than 200 mg daily (for normal renal function) for pulmonary infections and no less than 400 mg daily for those with coccidioidal meningitis or extrapulmonary disease.
Key Recommendations
Donors with active coccidioidomycosis and those with old granulomas harboring viable organisms, regardless of the presence or absence of a positive serology have the potential to transmit infection to the recipients.
Approach to diagnostic evaluation and management of donor-derived coccidioidomycosis is summarized in Supporting Figures S5 and S6, respectively.
Lipid formulations of amphotericin B represent the agents of choice for the treatment of life-threatening or rapidly progressive coccidioidomycosis whereas fluconazole or itraconazole may be employed for most nonlife-threatening infections. Treatment should be followed by indefinite secondary prophylaxis, preferably using fluconazole.