Why do echinocandins fail? Identifying key predictors to improve clinical outcomes of candida bloodstream infections: a retrospective multicenter cohort study

IF 4.3 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Infectious Diseases Pub Date : 2025-09-03 DOI:10.1016/j.ijid.2025.108046

Davide Fiore Bavaro , Lucia Diella , Alessandro De Angelis , Massimo Vanoni , Alessandra Belati , Laura De Santis , Linda Bussini , Laura Montemurro , Roberto Papale , Luigi Ronga , Maria Calabrò , Erminia Casari , Monica Stufano , Lidia Dalfino , Federica Tordato , Paola Morelli , Nadia Fusilli , Gianluca Castellani , Elena Costantini , Francesco Di Gennaro , Michele Bartoletti

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引用次数: 0

Abstract

Background

Echinocandins represent first-line therapy for Candida Bloodstream Infections (C-BSIs). Incidence 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.

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为什么电子邮件会失败？确定关键预测因素以改善念珠菌血流感染的临床结果：一项回顾性多中心队列研究。

背景：棘白菌素是治疗念珠菌血流感染（C-BSIs）的一线药物。治疗失败（TF）的发生率仍然很高，危险因素不明。目的：探讨棘白素TF对c - bsi的预测因素。方法：回顾性观察性多中心研究，纳入2020年6月1日至2023年6月30日在意大利四家医院接受棘白菌素治疗的所有C-BSI患者。主要结局：评估TF的预测因素，定义为：i)在治疗第5天转入ICU或器官功能障碍恶化；(二)持续C-BSI;iii)因任何原因停用棘白菌素；iv)在治疗期间出现念珠菌感染的新部位。次要结局：90天全因死亡率。采用Cox回归和治疗效应，以及治疗加权逆概率（IPTW）来调整队列治疗分配偏倚。结果：总共有218名患者入组。中位（第一季度-第三季度）年龄为72岁（56-78岁），55%为男性。在33%和63%的病例中，报告了脓毒性休克和非白色念珠菌菌株引起的c - bsi。重要的是，根据临床判断，68例（31%）患者接受了高剂量棘白菌素治疗（“HDE”：比标准剂量增加30-50%）。82例（38%）发生TF；90天全因死亡率为30%，tnf组（p30）或血清白蛋白浓度≤2.5 gr/dL显著高于tnf组（p < 0.05）。结论：多种临床和微生物因素可影响棘白菌素TF。有趣的是，对于有棘白菌素TF风险的患者，HDE可能具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Infectious Diseases 医学-传染病学

CiteScore

18.90

自引率

2.40%

发文量

1020

审稿时长

30 days

期刊介绍： International Journal of Infectious Diseases (IJID) Publisher: International Society for Infectious Diseases Publication Frequency: Monthly Type: Peer-reviewed, Open Access Scope: Publishes original clinical and laboratory-based research. Reports clinical trials, reviews, and some case reports. Focuses on epidemiology, clinical diagnosis, treatment, and control of infectious diseases. Emphasizes diseases common in under-resourced countries.