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

Abstract

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.

Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment

“…(2) The relationship between sterile CSF culture and mortality is still controversial. Although rapid clearance of CSF Cryptococcus is associated with a high survival rate, some studies also indicated that high sterile culture rate was not associated with a low survival rate of patients 33,34 and was even associated with high mortality. 35 Notably, AIDS patients had a trend of high 90-day mortality compared with CM patients without predisposing disease and non-AIDS patients with other predisposing disease although no statistical significance was found (log-rank p = .174).…”