High mortality and amphotericin B-related nephrotoxicity in cerebral cryptococcosis in a low-resource neurology referral center: a prospective cohort study

Background Cerebral cryptococcosis (neurocryptococcosis) is an important cause of meningoencephalitis among immunocompromised people worldwide, particularly in regions with limited access to antiretroviral therapy and to optimal antifungal agents. Methods Prospective observational cohort study of consecutive adults hospitalized with cerebral cryptococcosis at the Neurology Service of the Servicio Autónomo Hospital Universitario de Maracaibo, Maracaibo, Zulia, Venezuela (January 2022 to July 2024). Data were collected using a validated instrument; modified Rankin Scale (mRS) assessed disability at discharge. Results Sixty-two patients (mean age 36.5 ± 12.9 years; 66.1% male) were included; 72.6% were HIV-positive. All patients presented headache, neck stiffness and altered mental status. Mean CSF protein was 103.5 mg/dL, cell count 504.5 cells/mm 3 and glucose 33.8 mg/dL. Amphotericin B (daily regimen) was administered in 74.2% and fluconazole in 82.3%. Acute kidney injury (AKI) occurred in 59.7% and hypokalemia in 56.5%. In-hospital mortality was 46.8% (mRS 6). Mortality was higher in patients with AKI (35.5% vs. 11.3%; p = 0.015) and hypokalemia ( p = 0.017). Mortality tended to be lower with daily versus alternate-day amphotericin (10% vs. 45%; p = 0.297). Conclusion Cerebral cryptococcosis in this referral setting affects predominantly young, HIV-infected adults and is associated with high mortality and disability. Amphotericin B-related nephrotoxicity and hypokalemia were common and associated with worse outcomes, underscoring the need for nephroprotection protocols and optimized antifungal strategies in resource-limited settings.