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.