Clinical Characteristics and Outcomes in Patients With Cryptococcaemia From a Large Population-Based Cohort.

Background: Cryptococcus bloodstream infections (BSIs) or cryptococcaemia are severe opportunistic infections with high mortality, predominantly affecting immunocompromised individuals or those with end-stage organ disease. Population-based studies examining infection trends and associations between host factors, geography, antifungal resistance, and clinical outcomes are few.

Methods: Blood cultures with growth of Cryptococcus species were retrospectively identified over a 20-year period (January 1, 2000-December 31, 2019) from a state-wide database. Clinical, microbiological and outcome information was also obtained. Survival analyses were used to establish associations between clinical or microbiological characteristics and mortality.

Results: A total of 118 cryptococcaemia episodes (115 patients) were identified, with Cryptococcus neoformans complex causing 98 episodes (83.1%). HIV-associated infections represented 28 episodes (23.7%), with non-HIV episodes (n = 90) more likely to be associated with comorbidities including solid organ transplantation, malignancy, chronic kidney disease, and rheumatological conditions. Overall, 30-day all-cause mortality was 34%, with higher mortality in non-HIV-associated cases (41.7% vs. 12.5%, HR 0.29; 95% CI 0.09-0.94). Of C. neoformans complex isolates with a fluconazole MIC $\ge$ 8 mg/L, 6 (46%) were observed in the most recent 5-year period. Thirty-day (p = 0.85) and 1-year (p = 0.35) mortality increased in a stepwise fashion with increasing fluconazole MIC values in C. neoformans complex infection. Fifty-three episodes (49.1%) documented isolated cryptococcaemia. Patients with additional sites of infection, including CNS involvement, experienced longer hospital stays. Those living in a regional or remote area (HR 1.33; 95% CI 0.68-2.61) or with older age (HR 1.02; 95% CI 1.00-1.04) experienced higher rates of death, although these findings were not statistically significant.

Conclusion: Cryptococcus BSI is a highly lethal condition, particularly among non-HIV infected individuals. We highlight the prognostic importance of blood culture collection in patients with suspected cryptococcal infection. Identifying contemporary risk factors for mortality is critical to understanding what drives poor outcomes. There is a need for continued surveillance of fluconazole susceptibility among Cryptococcus species.