Incidence, Risk Factors, and Outcomes of Candida Bloodstream Infections in Hematological and Oncological Patients
Authors: Wolf Sebastian , Weber Sarah , Janetta Aaron , Klein Friederike , Enssle Julius C. , Hogardt Michael , Kempf Volkard A. J. , Kessel Johanna , Vehreschild Maria J. G. T. , Steffen Björn , Oellerich Thomas , Serve Hubert , Scheich Sebastian 
Published: December 2024

Candida blood stream infections (BSI) in cancer patients are an important source of morbidity and mortality. While antifungal prophylaxis has reduced the overall incidence, it remains crucial to understand the clinical course, risk factors, and outcomes of Candida BSI. Moreover, direct comparisons of risk factors and outcomes between Candida and bacterial BSI are sparse.

In this single-center, retrospective cohort study conducted at a tertiary cancer center in Germany, we analyzed 637 BSI events in 403 patients with hematological and oncological diseases. We detected 29 (4.5%) Candida BSI episodes, while the remainder were bacterial BSI. The majority of patients (n=369, 91.5%) suffered from hematological malignancies with AML being the most frequent underlying disease (n=194, 48.14%). At the time of the BSI event, 289 (45.4%) were receiving first-line treatment, 199 (31.2%) were on second-line treatment, and 149 (23.4%) were on later lines. Additionally, 162 (25.4%) and 44 (6.9%) BSI events occurred within the first 100 days after allogeneic or autologous hematopoietic stem cell transplantation (HSCT), respectively.

The risk of death within 30 days was significantly higher for Candida BSI compared to bacterial BSI (HR 4.5, 95% CI 2.5-8.1, p&lt;0.001). When stratified by bacterial taxonomy and antibiotic resistance profile, only multi-drug resistant gram-negative organisms with carbapenem resistance (HR 8.1, 95% CI 4.3-15.3, p&lt;0.001) had a stronger impact on mortality followed by Candida BSI. Candida BSI patients were more often treated in later therapy lines (79.3% vs. 53.5%, p=0.01) and for relapsed or refractory disease (58.6% vs. 38.5%, p=0.048), more often with palliative intent (37.9% vs. 15.1%, p=0.003) compared to bacterial BSI.

Logistic regression identified hypoalbuminemia (HR 9.13, 95% CI 2.7-57), prior ICU/IMC stay (HR 3.91, 95% CI 1.38-9.65), palliative treatment (HR 3.42, 95% CI 1.52-7.4), parenteral nutrition (HR 2.44, 95% CI 0.9-5.5), prior allogeneic HSCT (HR 2.28, 95% CI 0.92-5.13), relapsed/refractory disease (HR 2.26, 95% CI 1.1-4.9), and later line treatment (HR 2.08, 95% CI 0.93-4.45) as significant univariate risk factors for Candida BSI (p&lt;0.1). No prior stem cell transplantation (HR 0.36, 95% CI 0.17-0.8), first-line therapy (HR 0.3, 95% CI 0.11-0.7), and de novo disease (HR 0.28, 95% CI 0.11-0.64) were associated with decreased risk. Multivariate analysis retained palliative therapy (HR 5.23, 95% CI 3.14-8.71), hypoalbuminemia (HR 9.02, 95% CI 4.23-19.2), and prior ICU/IMC stay (HR 4, 95% CI 2.31-6.92) as independent risk factors.

Following clinical or laboratory suspicion of infection, approximately half of the patients received an empirical antifungal therapy (n = 16, 55.2%). As part of the first empirical escalation in case of persistent fever beyond 48 hours, an additional 7 (24.1%) patients received antifungal therapy. In sum, in the vast majority of Candida BSI events (n = 23, 79.3%), antifungal therapy was initiated within the first 72 hours after clinical signs of infection.

Taken together, we evaluate in this study outcome and risk factors for Candida BSI in a large cohort of hematological and oncological patients. In this cohort consisting mainly of patients with AML, Candida BSI, albeit relatively rare, was associated with a significantly worse 30 days overall survival. Key risk factors for the development of Candida BSI are advanced disease, later therapy lines and indicators of impaired functional status. Poor outcome after Candida BSI was observed despite initiation of adequate antifungal therapy within 72 hours of infection onset further supporting the role of increased host susceptibility in this patient population.