在唑类药物有效治疗曲霉菌时代侵袭性镰刀菌病在白血病患者中的情况：发病率不断上升，频繁出现突破性感染，且无改善的预后。

Invasive fusariosis in patients with leukaemia in the era of mould-active azoles: increasing incidence, frequent breakthrough infections and lack of improved outcomes.

机构信息

Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

J Antimicrob Chemother. 2024 Feb 1;79(2):297-306. doi: 10.1093/jac/dkad377.

DOI:10.1093/jac/dkad377

PMID:38073151

Abstract

OBJECTIVES

Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients.

METHODS

We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis.

RESULTS

Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; P < 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; P = 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; P < 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; P = 0.04).

CONCLUSIONS

IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.

摘要

目的

在持续免疫抑制的情况下，患有白血病和侵袭性镰刀菌病（IF）的患者历史上预后较差。在此，我们回顾性分析了在当代白血病患者队列中鲜有研究的 IF 的发生率、表现和结局。

方法

我们在 MD 安德森癌症中心确定了 2009 年至 2021 年间确诊或疑似 IF 的成年白血病患者。使用多变量逻辑回归模型确定 IF 诊断后 42 天死亡率的独立危险因素。结合历史数据，使用泊松回归分析估算过去 23 年来 IF 的年发生率密度。

结果

在 140 例 IF 白血病患者（114 例确诊）中，118 例（84%）为复发/难治性白血病，124 例（89%）在 IF 诊断时中性粒细胞减少。100 例（71%）患有肺部 IF，88 例（63%）患有播散性 IF，48 例（34%）患有真菌血症。合并感染很常见（55%）。89 例（64%）患者发生突破性 IF 至真菌活性三唑类药物。大多数患者（84%）接受联合抗真菌治疗。中性粒细胞恢复[校正比值比（aOR），0.04；95%置信区间（CI），0.01-0.14；P<0.0001]、肺部 IF（aOR，3.28；95%CI，1.11-9.70；P=0.032）和高 SOFA 评分（aOR，每增加 1 分 1.91；95%CI，1.47-2.50；P<0.0001）是 42 天死亡率的独立预测因素。从 1998 年到 2021 年，IF 的发生率密度以每年 1.03 的比率显著增加（95%CI，1.01-1.06；P=0.04）。