Chai Louis Yi Ann, Kullberg Bart Jan, Earnest Arul, Johnson Elizabeth M, Teerenstra Steven, Vonk Alieke G, Schlamm Haran T, Herbrecht Raoul, Netea Mihai G, Troke Peter F
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, the Netherlands ; Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore, Singapore.
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, the Netherlands.
PLoS One. 2014 Feb 28;9(2):e90176. doi: 10.1371/journal.pone.0090176. eCollection 2014.
An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response.
目前有更多改良的抗真菌药物可用于治疗侵袭性曲霉病(IA)。虽然连续半乳甘露聚糖指数(GMI)测量可用于监测治疗反应,但不同抗真菌治疗方案对半乳甘露聚糖水平的影响程度尚不清楚。在一项多中心临床试验中,对147例接受伏立康唑(VCZ)或传统两性霉素B(CAB)治疗的IA患者,我们对与结局相关的GMI趋势进行了事后分析。采用广义估计方程方法来估计患者体内GMI效应大小随时间的变化。与仅接受CAB治疗的患者相比,接受VCZ初始治疗且12周后治疗反应良好的患者在第1周和第2周时GMI值下降更早(分别为p = 0.001和0.046)。在随机治疗结束时(EORT),这是所有从随机初始治疗(CAB或VCZ)转换为另一种抗真菌药物的患者的预设二级评估点,在CAB初始治疗的患者中,治疗失败与第1周和第2周时GMI升高相关(分别为p = 0.022和0.046)。这些不同的趋势突出了使用不同抗真菌药物时GMI动力学的差异及其与IA治疗反应的关系。