Use of Intrathecal Amphotericin for Coccidioidal Meningitis

Area of Science:

• Infectious Diseases
• Neurology
• Pharmacology

Background:

• Coccidioidomycosis cases, particularly coccidioidal meningitis (CM), are rising in the US.
• The role of intrathecal (IT) amphotericin in treating CM alongside azole therapy remains unclear.
• This study investigates the association between IT amphotericin use and mortality in CM patients.

Purpose of the Study:

• To evaluate the association between intrathecal amphotericin administration and mortality in patients with coccidioidal meningitis.
• To understand the impact of IT amphotericin in the context of concurrent azole therapy.
• To identify factors associated with mortality in CM patients receiving advanced treatments.

Main Methods:

• Retrospective chart review of adult patients with laboratory-proven CM at Stanford Healthcare (2008-2023).
• Analysis included patients receiving azole therapy, with a subgroup also receiving IT amphotericin.
• Statistical analysis involved Kaplan-Meier curves and Cox regression to assess mortality predictors.

Main Results:

• Of 57 patients, 47.4% received IT amphotericin. These patients had more severe initial disease markers and higher rates of IV liposomal amphotericin and corticosteroid use.
• IT amphotericin use was significantly associated with increased mortality (HR, 13.9).
• Older age, IT amphotericin, and corticosteroid use were independent predictors of mortality, with a significant interaction between IT amphotericin and corticosteroids.

Conclusions:

• Intrathecal amphotericin use in CM patients on azole therapy correlates with higher mortality rates.
• This suggests IT amphotericin may be used for more refractory disease.
• Development of novel therapeutic approaches is crucial for patients with progressive CM despite current treatments.