Background: Cryptococcal infections have been studied in depth in patients with HIV, but outcomes and optimal treatments in other immune-suppressed patients are not well characterized. We performed a large multicenter, prospective cohort study of HIV-negative patients with cryptococcosis with aim to describe the outcomes and treatment practices.
Methods: Investigators from 25 strategically placed hospitals throughout the United States assembled to capture cases and report outcomes in a modified prospective cohort study, using internet-based case report forms. Data on comorbidities, predisposing factors, infection characteristics, survival, disability and outcomes were tabulated. Cumulative morbidity was modeled using novel risk methods and recurrent event analyses.
Results: Data from 127 of over 150 patients enrolled to date are presented here. Patients were predominantly male (66%), and 101 (82%) were immunocompromised, with most frequent prior therapies including receipt of cytotoxic chemotherapy (n = 77, 61%) and solid organ transplant (n = 38, 30%). Most patients were enrolled from the Southern U.S. region (n=75, 59%). Disease involved only the lungs in 17 (13%). Diagnosis was delayed beyond 1 month from presentation in a large proportion of patients (26%). Therapy and outcomes were described in 97 patients who were followed prospectively. The majority received a polyene based treatment (63%), with 37% receiving only azoles. Mortality at 100 days was 20%. Prospective outcomes are shown in Figure 1, with each line representing patients. Cumulative neurologic morbidity was significant, both with regards to complications of high-pressure management and functional decline. Serial assessment of Montreal Cognitive Assessment (MoCA) scores showed that patients who were enrolled with impaired cognition (78%) were slow to improve, and some did not return to normal, even after a year of therapy.
Conclusion: HIV negative patients with cryptococcosis that involves the CNS have decidedly poor outcomes, especially with consideration of cumulative neurologic morbidity. Methods demonstrated in this study, including use of prospective cohort design and recurrent event analyses to understand cumulative morbidity, provide a useful template to better understand the clinical approach to poorly evaluated infectious diseases.
P. Williamson, None
J. E. Bennett, None
J. Garcia-Diaz, None
D. Ostrander, None
C. Y. Huang, None
Y. Sun, None
K. A. Marr, None