Evaluating clinical outcome in non-HIV associated cryptococcal meningitis with negative CSF culture using microscopic quantitative cryptococcal counting

Abstract

Background: Non-HIV associated cryptococcal meningitis (CM) patients with negative cerebrospinal fluid (CSF) culture lack validated biomarkers for outcome assessment. Baseline CSF cryptococcal count via India ink staining correlate with disease progression, but the role of cryptococcal clearance rate remains unclear in this population.

Methods: We retrospectively collected data from 594 non-HIV associated CM patients from the Third Affiliated Hospital of Sun Yat-sen University. 111 non-HIV associated CM patients with negative CSF culture were included to analyse. We focused on analyzing the association between cryptococcal clearance rate and outcome.

Result: Baseline high log₁₀ CSF cryptococcal count (OR: 2.939, 95%CI 1.574-5.488, p=0.001) and slow rate of cryptococcal clearance (OR: 92.228, 95%CI 6.453-1318.128, p=0.001) were associated with unsuccessful outcomes at 2 weeks after admission. The baseline high log₁₀ CSF cryptococcal count (OR: 1.520, 95%CI 1.045-2.211, p=0.029), slow rate of cryptococcal clearance (OR: 162.896, 95%CI 10.028-2646.031, p=0.001) and hearing impairment at baseline (OR: 8.683, 95%CI 1.294-58.291, p=0.026) were associated with unsuccessful outcomes at 10 weeks after admission. And hearing impairment at baseline (log-rank test, p=0.007), baseline log₁₀ CSF cryptococcal count ≥1.52/ml (log-rank test, p=0.033) were associated with no clinical cure within 1 year after admission.

Conclusion: Rate of cryptococcal clearance based on India ink staining may be a marker for short-term outcomes in non-HIV associated CM patients with negative CSF culture. Monitoring this marker may optimize clinical management in this challenging subgroup. Notably, its strengthened association at 10 weeks reflects sustained prognostic value, while the attenuated effect of baseline count suggests diminishing early impact.

Keywords: Cryptococcal meningitis; India ink staining; outcome; rate of cryptococcal clearance.