Clinical and microbiologic outcomes of central nervous system cryptococcosis: Re-examining the need for a 2-week cerebrospinal fluid analysis

Background: Cryptococcus spp. infection involving the central nervous system (CNS) is associated with poor outcomes. Current guidelines recommend repeating a cerebrospinal fluid (CSF) fungal culture after 2 weeks of treatment to evaluate for clearance. However, this practice has not clearly been associated with outcomes. Objectives: We sought to assess the relationship between CSF fungal clearance at 2 weeks and 12-month mortality in patients with CNS cryptococcosis. Methods: This is a retrospective cohort study from 2011 to 2020 of patients with CNS cryptococcosis. Factors associated with 12-month mortality were assessed with Fisher’s exact test for categorical variables and Mann–Whitney test for continuous variables. Results: Among 51 patients with CNS cryptococcosis, 42 (82.4%) were initially CSF culture positive. Among 27 patients with follow-up CSF culture at 2 weeks, 6 (22.2%) had a positive result. Factors associated with a positive CSF culture at 2 weeks were an initial CSF cryptococcal antigen titre ≥1:2560, fungaemia, and an elevated intracranial pressure requiring therapeutic lumbar punctures. The 12-month mortality rate was 33.3%, and this was significantly associated with baseline fungaemia, extra-CNS cryptococcal involvement and requirement of intensive care unit level of care. Lack of CSF culture clearance by 2 weeks was not associated with 12-month mortality. Conclusions: CNS cryptococcosis has a high mortality rate. A markedly elevated CSF cryptococcal antigen, and opening CSF pressure was associated with lack of CSF culture clearance at 2 weeks of treatment. Severe disseminated disease and cryptococcemia were associated with 12-month mortality.