Insights into current coccidioidomycosis therapeutic pathways.

Coccidioidomycosis is a systemic fungal infection caused by Coccidioides immitis and Coccidioides posadasii, which are endemic to the Southwestern United States and parts of Mexico, Central, and South America. While oral fluconazole is widely recommended as first-line therapy, treatment failure is not uncommon for severe manifestations. This study aims to characterize antifungal treatment pathways, identify factors associated with treatment switches, and compare outcomes based on treatment courses. A retrospective cohort study was conducted using the TriNetX database with individual de-identified clinical data. Using International Classification of Diseases, Tenth Revision, Clinical Modification codes, we identified patients diagnosed with coccidioidomycosis between January 2010 and March 2024. "Treatment switches" were defined as receiving a different antifungal agent for at least three consecutive days after an initial regimen. Patient demographics, comorbidities, hospitalizations, ICU admissions, and mortality were assessed. A total of 1,909 patients met the inclusion criteria, with 1,581 having complete treatment pathway data. The majority (87.4%) began treatment with fluconazole, followed by amphotericin B (6.5%) and echinocandins (2.3%); 11.2% underwent at least one treatment switch. The most common switches were fluconazole to posaconazole (2.2%) and amphotericin B to fluconazole (1.8%). Coccidioidal meningitis patients switched from fluconazole had increased rates of ICU admission and hospitalization but similar 1-year mortality compared to fluconazole monotherapy. Fluconazole remains the first-line antifungal for coccidioidomycosis, followed by amphotericin B. Most patients required solely fluconazole treatment. While many factors are involved in therapy choice, optimization of therapeutic strategies after initial fluconazole treatment may be necessary for the future, especially for severe disease.