Population-based longitudinal study over two decades of Candida and Candida-like species bloodstream infection reveals gender and species differences in mortality, recurrence and resistance

Background: The global burden of bloodstream infection (BSI) due to Candida, and species previously classed as Candida (Candida-like species) is substantial. Recent emergence of Candida auris, fluconazole-resistant Candida parapsilosis and echinocandin-resistant Nakaseomyces glabratus emphasise the importance of global and regional surveillance. Methods: Blood cultures with growth of Candida/Candida-like species in Queensland, Australia (population ≈ 5 million) over a 20-year period (1 January 2000–31 December 2019) were retrospectively identified. Clinical, microbiological and outcome information was obtained from state-wide databases. Cox proportional and Fine-Gray subdistribution hazard models were used to construct hazard ratios for 30-day all-cause case fatality and 1-year recurrence, respectively. Results: A total of 2586 episodes (2420 patients) of Candida/Candida-like bloodstream infection (Ca-BSI) were identified; 249 episodes (9.5%) were in children. Candida albicans and C. parapsilosis complex reduced in frequency, whilst N. glabratus and Candida dubliniensis increased during the study. Of 1836 isolates tested, fluconazole (3.2%) and echinocandin (0.7%) resistance rates were low, with a decrease in fluconazole resistance observed from the first half of the study period to the latter half (4.5% versus 2.2%, P<0.01). Overall, 30-day all-cause mortality (21%) was unchanged: C. parapsilosis complex (aHR 0.44, 95% CI 0.32–0.60) was associated with decreased mortality, while C. tropicalis (aHR 1.35, 95% CI 0.95–1.93) was associated with an increase. Only 3.1% episodes demonstrated recurrence of Ca-BSI within one year. Presence of uncommon Candida species (aSHR 6.60, 95% CI 2.99–14.56) and an endovascular source of infection (aSHR 4.42, 95% CI 1.87–10.46) were associated with recurrence, while male gender (aSHR 0.57, 95% CI 0.35–0.92) was protective. Resistance to fluconazole (3.2% vs 3.5%, P=0.58) and echinocandins (0.6% vs 2.0%, P=0.05) was higher in recurrent Ca-BSI episodes. Females had a higher rate of fluconazole resistance (4.1% versus 2.4%, P=0.02). Conclusions: Our study highlights important shifts in causative species and resistance patterns of Ca-BSI which impacts clinical management. Antifungal resistance rates were low overall. The identification of new modifiable and non-modifiable risk factors for recurrence and mortality provides opportunities to examine new strategies to improve patient outcomes.