Morphology: Dimorphic fungus — mold with arthroconidia in soil; spherules (10–80 μm) packed with endospores in tissue at 37°C. Spherules pathognomonic on histopath.
Typical drugs
- #1Fluconazole— First-line for symptomatic primary pulmonary, dissemination, and chronic disease (400 mg/d, often higher).
- #2Itraconazole— Alternative azole; arguably better for skeletal disease.
- #3Amphotericin B (liposomal)— Severe pulmonary, refractory disease, or pregnancy.
- #4Voriconazole— Salvage.
- #5Posaconazole— Salvage.
Empiric therapy when resistant
Refractory or CNS disease: high-dose fluconazole (≥800 mg/d) or switch to voriconazole/posaconazole. CNS coccidioidomycosis = LIFELONG suppression with fluconazole. Intrathecal amphotericin historically used but rarely needed now.
Resistance notes
Resistance is uncommon; treatment failure usually reflects under-dosing, non-adherence, or immune suppression. Lifelong therapy for CNS disease — relapse common after discontinuation.
Pearls
"Valley Fever." Most cases asymptomatic or self-limiting flu-like illness with cough + fatigue + arthralgias ("desert rheumatism") + erythema nodosum / multiforme. Disseminated risk: African-American, Filipino, pregnant (3rd trimester), CD4 <250, transplant, anti-TNF, diabetic. Eosinophilia common. CNS disease — fluconazole LIFELONG (or switch to voriconazole). Travel history: ask about Arizona, Bakersfield, etc.