Failure of Early Mycological Clearance in HIV-Negative Cryptococcal Meningitis

Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood.

We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for Cryptococcus neoformans. Multivariate logistic regression was performed to analyze clinical features and laboratory and CSF findings of patients with CM with different EMC statuses. Random forest models were used to predict failure of EMC. All-cause mortality and clinical functional status were analyzed.

Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log₁₀ Cryptococcus count/mL, baseline CSF opening pressure (CSF-OP) >30 cm H₂O, and baseline serum creatinine were significantly associated with EMC failure. A parsimonious predictive rule given by the decision tree identified patients with CM with non-AmB-based therapy and baseline CSF-OP >30 cm H₂O as being at high risk of EMC failure. Incidence of all-cause mortality, the follow-up modified Rankin Scale, and Karnofsky performance status scores were not significantly related to EMC.

EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with log₁₀ Cryptococcus count/mL and CSF-OP >30 cm H₂O at baseline. Because of the small number of deaths, we are not able to comment on whether or not EMC is associated with mortality.