Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
J Clin Microbiol. 2012 Jul;50(7):2330-6. doi: 10.1128/JCM.06513-11. Epub 2012 May 2.
The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥ 0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively; P = 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (n = 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (P = 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
侵袭性曲霉病(IA)的治疗反应监测和预测较为困难。我们旨在确定疾病早期血清半乳甘露聚糖指数(GMI)的变化趋势是否有助于预测最终的临床结局。本研究纳入了多中心全球曲霉病研究的受试者,在抗真菌治疗后第 1、2 和 4 周分别检测基线和随访 GMIs。12 周的临床反应和生存率是主要的结局指标。采用广义估计方程方法分析 GMI 趋势。通过包含术前和术后概率的受试者工作特征曲线分析评估 GMI 截断值。在 202 例确诊为 IA 的研究患者中,71 例(35.1%)基线 GMI≥0.5。第 1 周时,12 周时最终治疗有效的患者的 GMI 显著低于无应答者(GMIs 分别为 0.62±0.12 和 1.15±0.22,P=0.035)。基线至第 1 周 GMI 降低>35%,则有良好临床反应的概率较高。对于治疗前 GMIs<0.5(n=131;64.9%)的 IA 患者,治疗期间 GMI 应保持较低水平,尽管接受抗真菌治疗,但第 2 周的绝对 GMI 升高至>0.5 则预示着临床结局较差。这里,基线至第 2 周 GMI 每增加 0.1 单位,无满意临床反应的可能性增加 21.6%(P=0.018)。总之,通过在抗真菌治疗的前 2 周内绘制早期 GMI 趋势,可以预测临床结局。这些发现对抗曲霉病的管理具有重要意义。