P485 Hiv-positive, solid organ transplant (SOT), and non-Hiv-positive/non-transplant (NHNT) associated with cryptococcosis in Brazil: First national multicenter cohort study
Authors: Cavassin Francelise Bridi , Vidal Jose Ernesto , Godoy Cássia Silva Miranda , Soares Renata Bastos Ascenço , Magri Marcello Mihailenko Chaves , Falci Diego Rodrigues , De Oliveira Carla Sakuma , Mendes Ana Verena Almeida , Baú-Carneiro João Luís , Queiroz-Telles Flávio 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objectives
To describe the characteristics, mortality, and therapeutic response among hospitalized patients with cryptococcosis in Brazil.

Methods
This is a multicenter retrospective cohort study of seven Brazilian public tertiary hospitals (Figure 1). Medical records of patients admitted from January 2014 to December 2019 were evaluated. Confirmed cases of the first episode of cryptococcosis were included. Hosts were classified as HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT). Mortality was defined as the time of patient admission to in-hospital death from any cause. Statistical analysis was performed using the software R and JAMOVI.

Results
A total of 384 patients were included; the median (25th-75th) age was 39 (31-48) years and 283 (73.7%) were men. Hosts were 304 (79.2%) HIV-positive, 16 (4.2%) SOT, and 64 (16.7%) NHNT. More frequent diagnosis tools were culture, direct microscopic examination of infected body fluids using India ink, histological examination of tissue samples, and detection of cryptococcal polysaccharide antigen in body fluids (CrAg) using latex. Central nervous system (CNS) cryptococcosis had a significantly higher counting level across disease categories, with 313 cases or 81.5%. NHNT were more likely to have CNS cryptococcosis than people HIV-positive (84.4% vs. 81.9%, respectively). SOT patients had more pulmonary form infections (31.2%) as compared with HIV-positive (3.3%) and NHNT (1.6%). Other extrapulmonary sites category had HIV-positive and NHNT basically the same percentage of disease involvement (14%) compared with SOT (6.2%) (P &lt; .001, Figure 2). Among cases with identification of specie, 56% were Cryptococcus neoformans and 4.4% were C. gattii. A total of 271 (70.6%) patients were discharged home with total or partial improvement and 113 (29.4%) patients died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT patients was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with AMB had the conventional deoxycholate mainly in combination with fluconazole (234, 84.2%). Only 80 (22.3%) patients received an AMB lipid formulation (liposomal AMB, n = 35 and AMB lipid complex, n = 45). The median (25th-75th) length of AMB therapy was 20 (14–32) days. Death patients had more age when compared with discharged-to-home cases (43 vs. 38 years, P &lt; .002). Patients with CNS cryptococcosis had lower mortality (83/313, 26.5%) when compared with the other categories [pulmonary, 5/16 (31.2%) and other extrapulmonary sites, 25/55 (45.4%)] (P = .017). Survival benefits were seen for patients who received monotherapy or combination therapy. However, D-AMB alone showed a higher mortality rate, although not statistically significant (P = .537).

Conclusion
HIV infection is the most important condition among patients with cryptococcosis in Brazil and CNS involvement is the commonest manifestation in all hosts, mainly HIV-positive and NHNT. The proportion of pulmonary cryptococcosis is relevant in SOT patients. Mortality was high in all categories of hosts. Understanding the epidemiology and characteristic of patients admitted to our hospitals will help to understand the burden and causes of mortality and identify strategies to improve this scenario. Optimized diagnosis (i.e., lateral flow assay) and treatment (i.e., AMB lipid formulation plus flucytosine) are urgently necessary for our setting.