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Coccidioidal meningitis: clinical presentation and management in the fluconazole era
Glenn Mathisen1, Aaron Shelub, Jonathan Truong
1From Cedars Sinai-UCLA Affilialted Multicampus Infectious Disease Program (GM, AS, JT, CW), Los Angeles; Cedars Sinai Medical Center, Los Angeles; Olive View-UCLA Medical Center (GM, JT, CW), Sylmar; VA West Los Angeles Medical Center, Los Angeles; Los Angeles County Department of Public Health (CW), Los Angeles; and Southern California Kaiser Permanente Medical Group (JT), Los Angeles, California.
Abstract:
Despite the advent of new antifungal agents, coccidioidal meningitis (CM) remains a difficult-to-treat condition with significant morbidity and mortality. In this study we directly compare the clinical presentation and management of patients with Coccidioides immitis meningitis in the azole era (after 1980) to that of a cohort of patients from the pre-azole era. We reviewed 30 CM cases seen at 3 Los Angeles hospitals between the years 1993 to 2008 ("2008 cohort") and compared them to 31 patients ("1980 cohort") described by Bouza et al in a previous study. The demographics and clinical presentation of patients in the 2008 cohort were similar to those of the 1980 cohort except for a higher incidence of Hispanic patients (2008: 53% vs. 1980: 6%) and a greater percentage of patients with underlying, predisposing clinical conditions (2008: 66% vs. 1980: 32%). Ten patients in the 2008 cohort had human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), a condition not reported in the earlier study. Laboratory findings were similar between the 2 groups except for a lower incidence of peripheral leukocytosis and eosinophilia in the 2008 group.There were marked differences in drug treatment between the 2 eras. In the 2008 cohort, 29 patients received fluconazole therapy: 13 were treated with fluconazole monotherapy, and 16 received a combination of fluconazole and intravenous amphotericin B. Although almost all patients (29/31) in the 1980 cohort received intrathecal amphotericin B, only 3 patients in the 2008 study received amphotericin B via this route. With respect to complications of CM, a similar percentage of patients in each cohort developed complications such as stroke and hydrocephalus. The 2008 cohort (40%) had similar mortality compared to patients in the 1980 study (39%); survivors in both groups experienced significant impairment of activities of daily living. Although recommended as first-line therapy for CM, azole-based therapies are not curative and do not necessarily prevent complications associated with the disease.CM remains a serious illness with a high rate of morbidity and mortality. Immunocompromised individuals, especially those with HIV/AIDS, are at special risk for CM and represent a greater share of the overall population with this condition. Despite the clear advantages of azole treatment in CM, new therapeutic approaches are needed to provide definitive cure and to reduce the need for long-term suppressive therapy.
Insights
Coccidioidal meningitis (CM) remains a severe fungal infection with high mortality. While azole antifungals are used, they are not curative, necessitating new treatments for coccidioidomycosis of the brain.
Area of Science:
- Infectious Diseases
- Mycology
- Neurology
Background:
- Coccidioidal meningitis (CM) presents a significant challenge due to high morbidity and mortality.
- Comparing CM treatment and outcomes before and after the widespread use of azole antifungals is crucial for understanding treatment evolution.
Observation:
- The 2008 cohort showed a higher incidence of Hispanic patients and those with predisposing conditions, including HIV/AIDS, compared to the 1980 cohort.
- Fluconazole was the primary treatment in the 2008 cohort, contrasting with the prevalent intrathecal amphotericin B use in the 1980 cohort.
- Despite treatment differences, complication rates (stroke, hydrocephalus) and mortality remained similar between the two eras.
Findings:
- Azole-based therapies, while advantageous, do not offer a definitive cure for coccidioidal meningitis.
- Patients treated in the azole era (post-1980) still experienced significant long-term disability.
Implications:
- Immunocompromised individuals, particularly those with HIV/AIDS, are at increased risk for severe CM.
- Novel therapeutic strategies are urgently needed to achieve a definitive cure for CM and reduce reliance on long-term suppressive antifungal therapy.
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