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Background: The epidemiology of candidemia is evolving with raising concern about the emergence of intrinsically resistant non-albicans Candida species and acquisition of antifungal resistance. In addition to microbiological surveys, epidemiological studies including clinical data are needed to assess the impact of candidemia on morbidity and mortality., Objectives: To assess the clinical and microbiological trends of candidemia in a Swiss university hospital., Patients/methods: This single-centre retrospective study compared the incidence of candidemia, Candida species distribution, antifungal resistance profiles, clinical characteristics and outcomes between two periods separated by one decade., Results: A total of 170 candidemic episodes were included (68 from period 1, 2004-2006, and 102 from period 2, 2014-2017). Incidence of candidemia (0.85 to 0.97 episode/10,000 patient-days), species distribution (55%-57% C albicans) and antifungal susceptibilities remained unchanged. During period 2, candidemia was more frequently observed in intensive care units (ICU, 38% vs 19% in period 1, P = .01) and amongst older patients (median age 68 vs 59 years old, P < .01) with more immunosuppressive conditions (24% vs 9%, P = .01). Candidemia in period 2 was more frequently followed by septic shock (23% vs 7% in period 1, P = .01) and ICU admission (42% vs 12%, P < .01) and was associated with higher mortality (34% vs 18%, P = .03). Overall, factors associated with mortality in multivariate analyses included cirrhosis, solid malignancies and ICU stay at the time of candidemia., Conclusions: Despite stable incidence, species distribution and antifungal resistance of candidemia, an epidemiological shift of the disease towards older and more critically ill patients was observed, with higher mortality rates., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

Background: Candidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs., Methods: This prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia., Results: One hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia., Discussion: While this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU)., Conclusion: This study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients' management strategies and fungal epidemiology.

Objectives: Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics., Methods: A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria., Results: 43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock. Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal mucositis (multivariate OR 5.25, 95%CI 2.23-12.40, p < 0.001) and graft-versus-host-disease (6.25, 1.00-38.87, p = 0.05), immunosuppression (2.42, 1.03-5.68, p = 0.043), and parenteral nutrition (2.87, 1.44-5.71, p = 0.003). Non-albicans Candida were isolated in 58% BTC vs. 35% non-BTC (p = 0.005). 63% of 16 BTC occurring after 10-day fluconazole were non-susceptible (Candida glabrata, Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following shorter exposure (7.10, 1.60-31.30, p = 0.007). Median fluconazole MIC was 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy., Conclusions: Outcomes of BTC and non-BTC were similar. Fluconazole non-susceptible BTC occurred in three out of four cases after prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration and rapid de-escalation of empirical therapy in BTC after short fluconazole exposure., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)