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

## TL;DR

This study finds high mortality and kidney damage from a common antifungal drug in patients with brain cryptococcosis in a low-resource setting.

## Contribution

The study highlights the association between amphotericin B-related nephrotoxicity and poor outcomes in cerebral cryptococcosis in a low-resource hospital.

## Key findings

- High in-hospital mortality (46.8%) was observed in cerebral cryptococcosis patients.
- Acute kidney injury and hypokalemia were common and linked to higher mortality.
- Daily amphotericin B use was associated with lower mortality compared to alternate-day use.

## Abstract

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.

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.

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/mm3 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).

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.