Background: Echinocandins represent first-line therapy for Candida Bloodstream Infections (C-BSIs).In-cidence of treatment failure (TF) remains high with unclear risk factors. Aim: to evaluate predictors of echinocandin TF for C-BSIs. Methods: Retrospective observational multicenter study, enrolling all patients with C-BSI treated with echinocandin from 01/06/2020 to 30/06/2023 in four Italian Hospitals. Primary outcome: to evaluate predictors of TF defined as a composite of: i)transfer to ICU or any worsening in organ dysfunction at day 5 of therapy; ii)Persistent C-BSI; iii)Echinocandin discontinuation for any reason; iv)Onset of a new infection site by Candida spp. during treatment. Secondary outcome: 90-day all-cause mortality. Cox regression and treatment-effect were used, along with inverse-probability of treatment-weighting (IPTW) to adjust cohort treatment-assignment bias. Results: Overall, 218 patients were enrolled. Median (q1-q3) age was 72 (56-78), 55% male. In 33% and 63% of cases, septic shock at presentation and C-BSIs by non-albicans strains were reported. Importantly, 68 (31%) patients received high dosage echinocandin ("HDE": increase of 30-50% of standard dosage), according to clinical judgement. Eighty-two (38%) experienced TF; 90-day all-cause mortality was 30%, significantly higher in TF-group ( P < 0. 001). At multivariable Cox-regression analysis, obesity, septic shock, and increased MIC to echinocandins were predictors of TF; presence of removable intravascular devices and HDE resulted protective. After adjustment by inverse-probability of treatment-weighting, HDE still reduced TF risk in patients admitted to the ICU, with SOFA score<6, BMI > 30, or with serum albumin concentration <= 2,5gr/dL. Conclusion: Several clinical and microbiological factors could influence the echinocandin TF. Interestingly. in patients at risk for echinocandin TF, HDE may be protective. (c) 2025 The Author(s) Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/try-nc-nd/4.0/)
Why do echinocandins fail? Identifying key predictors to improve clinical outcomes of candida bloodstream infections: a retrospective multicenter cohort study
Bavaro, Davide Fiore;Bussini, Linda;Cento, Valeria;Cattaneo, Dario;Cecconi, Maurizio;Bartoletti, Michele
2025-01-01
Abstract
Background: Echinocandins represent first-line therapy for Candida Bloodstream Infections (C-BSIs).In-cidence of treatment failure (TF) remains high with unclear risk factors. Aim: to evaluate predictors of echinocandin TF for C-BSIs. Methods: Retrospective observational multicenter study, enrolling all patients with C-BSI treated with echinocandin from 01/06/2020 to 30/06/2023 in four Italian Hospitals. Primary outcome: to evaluate predictors of TF defined as a composite of: i)transfer to ICU or any worsening in organ dysfunction at day 5 of therapy; ii)Persistent C-BSI; iii)Echinocandin discontinuation for any reason; iv)Onset of a new infection site by Candida spp. during treatment. Secondary outcome: 90-day all-cause mortality. Cox regression and treatment-effect were used, along with inverse-probability of treatment-weighting (IPTW) to adjust cohort treatment-assignment bias. Results: Overall, 218 patients were enrolled. Median (q1-q3) age was 72 (56-78), 55% male. In 33% and 63% of cases, septic shock at presentation and C-BSIs by non-albicans strains were reported. Importantly, 68 (31%) patients received high dosage echinocandin ("HDE": increase of 30-50% of standard dosage), according to clinical judgement. Eighty-two (38%) experienced TF; 90-day all-cause mortality was 30%, significantly higher in TF-group ( P < 0. 001). At multivariable Cox-regression analysis, obesity, septic shock, and increased MIC to echinocandins were predictors of TF; presence of removable intravascular devices and HDE resulted protective. After adjustment by inverse-probability of treatment-weighting, HDE still reduced TF risk in patients admitted to the ICU, with SOFA score<6, BMI > 30, or with serum albumin concentration <= 2,5gr/dL. Conclusion: Several clinical and microbiological factors could influence the echinocandin TF. Interestingly. in patients at risk for echinocandin TF, HDE may be protective. (c) 2025 The Author(s) Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/try-nc-nd/4.0/)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
