P253 Features of Cryptococcosis in human immunodeficiency virus-negative patients, France 1985-2020
Authors: Paccoud Olivier , Desnos-Ollivier Marie , Boukris-Sitbon Karine , Lanternier Fanny , Dromer Francoise 
Published: September 2022

Abstract

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM

Objectives
HIV-negative individuals make up an increasing proportion of cases of cryptococcosis in France, but the features of disease and outcomes in this population have yet to be characterized. We describe the presentations and outcomes according to host factors underlying cryptococcosis in HIV-negative individuals in France.

Methods
The French National Reference Centre for Invasive Mycoses and Antifungals has implemented nationwide surveillance of cryptococcosis since 1985 with the determination of the infecting serotype. We analyzed the characteristics of infection in HIV-negative patients diagnosed up to 2020. We also compared the demographic characteristics, presenting features, treatment regimen, and outcomes according to host factor and infecting serotype in patients diagnosed since 2005.

Results
The mean age of patients was 56.2 years, 60.8% were male, and 60.1% were born in Europe. Only 26 cases were due to Cryptococcus gattii, all others were caused by C. neoformans. Of the 1051 cases, 349 occurred in patients with malignancy (33.2%, including 268 patients with hematological malignancy, 69% of whom had lymphoid neoplasms), 205 occurred in solid-organ transplant (SOT) recipients (19.5%, including 147 kidney and 27 liver), and 298 occurred in patients with ‘other’ underlying factors (28.4%, including auto-immune disease (n = 86), end-stage liver or kidney disease (n = 47), sarcoidosis (n = 42), chronic pulmonary disease (n = 25), and diabetes mellitus (n = 16). A total of 19% of patients (n = 199) had no apparent underlying risk factor.
Among 632 patients diagnosed since 2005, there were significant differences according to the four major categories of risk factors (malignancy, SOT, others, and none) in terms of age, diagnostic methods, proportion of patients with positive cryptococcal antigen (CrAg), antigen titers, disease localization, treatment regimens, and 90-day mortality. In the diagnostic workup, a lumbar puncture and blood culture were performed for 96% and 64.2% of patients, respectively, more frequently for immunocompromised patients than those with no underlying host factor (P = .09 and P &lt;.001, respectively). SOT patients had more frequent central nervous system involvement (P &lt;.001), and positive serum CrAg detection with antigen titers &gt;1:512 (P &lt;.001). Patients with malignancy were significantly older (P = .0001) with more frequent fungemia (P = .007). Isolated lung infections (P = .002) and isolated skin lesions (P &lt;.001) were more frequent in patients with ‘other’ conditions and in those with no underlying factor, respectively. Immunocompromised patients were more likely to receive combination antifungals including flucytosine (66.7%, 45.4%, and 42.7% for SOT, malignancies, and ‘other’ conditions, respectively) compared with patients with no underlying factor (33.3%, P &lt;.001). Overall, all cause 90-day mortality was 27.0% (95% CI: 23, 3-31.0%). Patients with malignancy had the highest 90-day mortality (37.3%, &lt;0.001), compared with SOT recipients (23.7%), those with ‘other' conditions (24.7%), and those without underlying conditions (13.9%). Compared with patients with serotype D infections, those infected with serotype A were significantly younger (P = .004), more likely to be born in Africa (P &lt;.001), to have isolated pulmonary disease (P &lt;.005), and less likely to have isolated skin infections (P &lt;.001).

Conclusion
HIV-seronegative patients with cryptococcosis are a heterogeneous group of patients encompassing different disease characteristics and outcomes. Management of cryptococcosis in HIV-negative patients should be tailored to underlying host factors, disease localization, and infecting serotype.