Management, outcomes and predictors of mortality of Cryptococcus infection in patients without HIV: a multicentre study in 46 hospitals from Australia and New Zealand

Abstract Background Limited data exist regarding outcomes of cryptococcosis in patients without HIV with few studies having compared outcomes of Cryptococcus gattii, versus C. neoformans, infection. Methods We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019, and compared outcomes of C. gattii versus C. neoformans infections. Multivariable analysis identified predictors of mortality within one year. Results Of 426 patients, one-year all-cause mortality was 21%. C. gattii infection was associated with a lower mortality than C. neoformans (adjusted odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.23-0.95), whilst severe neurological symptoms at presentation was the strongest predictor of death (adjusted OR: 8.46, 95% CI: 2.99-23.98). Almost all (99.5%) patients with central nervous system (CNS) infection received induction antifungal therapy versus 27.7% of isolated pulmonary cryptococcosis. The commonest regimen in CNS disease was liposomal amphotericin B with flucytosine (93.8%, mean duration 31 ± 13 days). Among patients with CNS cryptococcosis, C. gattii infection was associated with higher risk of immune reconstitution inflammatory response (C-IRIS) than C. neoformans (21% versus 3%, p<0.001). Nineteen patients received amphotericin B-based re-induction therapy for suspected relapse but none had microbiological relapse. Serum cryptococcal antigen positivity and lung imaging abnormalities resolved slowly (resolution at one year in 25% and 34% of patients, respectively). Conclusion Compared with C. neoformans, C. gattii infection demonstrated lower mortality but higher C-IRIS risk in CNS infection. Severe neurological symptoms were the strongest predictor of mortality.