Increased cryptococcal meningitis mortality among HIV negative, non-transplant patients: a single US center cohort study

Abstract

Cryptococcal meningitis (CM) is an opportunistic fungal infection associated with human immunodeficiency virus (HIV) and other forms of immunosuppression. We lack a clear understanding of CM associated mortality among HIV-negative, non-transplant patients in the United States (US). This article compares clinical features and outcomes across HIV status in patients with laboratory-confirmed CM. Methods: A retrospective cohort study was performed that included adult patients with laboratory-confirmed CM treated at an academic tertiary hospital between January 2000 and September 2018. Those with a history of organ transplant or non-meningeal infections were excluded. Data were gathered on demographics, HIV status, clinical presentation, cerebrospinal fluid (CSF) profiles, neurological outcomes, hospital course, and mortality. Results: A total of 70 patients with cryptococcal disease were identified. Our final sample included 36 CM patients, mean age was 48.8 ± 13.2 years; of this group, 66.7% ( n = 24) had HIV. Median [interquartile range (IQR)] absolute CD4 count for the HIV group was 35 cells/μl (10–80 cells/μl). Non-HIV/non-transplant patients were significantly older ( p < 0.001) and had higher rates of altered mental status (AMS) on presentation (58.3% versus 25%, p = 0.05). Non-HIV patients/non-transplant patients had significantly higher CSF white blood cell (WBC) count ( p = 0.02), lower CSF glucose ( p = 0.005), and higher CSF protein ( p < 0.001) compared with HIV patients. There was no significant variation in temperature, blood pressure, WBC count, serum sodium, CSF opening pressure, length of stay, intensive care unit admission, or neurological outcomes. Overall, 90-day all-cause mortality was 19.4%: mortality rates were significantly higher in non-HIV/non-transplant patients at both 90 days (41.7% versus 8.3%, p = 0.017) and 1 year (41.7% versus 12.5%, p = 0.047). Conclusion: Compared with HIV-infected individuals, non-HIV/non-transplant CM patients have a higher CSF WBC count at the time of diagnosis, higher rates of AMS on presentation, and higher rates of 90-day and 1-year all-cause mortality. Further prospective research is needed to identify the hallmarks of CM in non-HIV/non-transplant patients to facilitate early identification and intervention.