Division of Infectious Diseases, Brigham & Women's Hospital, 75 Francis Street, PBB-A4, Boston, MA 02115, USA.
J Clin Microbiol. 2010 Apr;48(4):1255-60. doi: 10.1128/JCM.02281-09. Epub 2010 Feb 10.
Prognostic features of serum galactomannan (GM) remain poorly defined in patients with GM-positive invasive aspergillosis (GPA). We identified 93 patients with proven or probable invasive aspergillosis (IA) and GM values of >or=0.50 from January 2005 to March 2009. We used Cox modeling of time to 6- and 12-week mortality for the GM level at the time of diagnosis (GM(0)), GM decay in the week following diagnosis in 72 patients with >or=2 GM values, other predictors of mortality, and antifungal use during the week following diagnosis. Six-week mortality was 55% in the whole cohort and 43% in patients with >or=2 GM determinations. The hazard ratio (HR) of GM(0) per unit increase and 1-week GM decay per unit decline per week were 1.25 (95% confidence interval [CI], 1.01 to 1.54; P = 0.04) and 0.78 (95% CI, 0.63 to 0.96; P = 0.02), respectively, adjusting for other predictors of IA mortality; these values remained stable after adjusting for antifungal use and were predictive of all-cause mortality at 12 weeks with similar adjusted HR values. We conclude that the combination of GM(0) and 1-week GM decay is predictive of all-cause mortality in patients with GPA, independent of other traditional risk factors for mortality and antifungal exposure, supporting GM decay as a potential surrogate endpoint for future antifungal therapeutic trials.
在 GM 阳性侵袭性曲霉病 (GPA) 患者中,血清半乳甘露聚糖 (GM) 的预后特征仍未得到明确界定。我们从 2005 年 1 月至 2009 年 3 月期间确定了 93 例 GM 值>或=0.50 的确诊或拟诊侵袭性曲霉病 (IA) 和 GM 阳性患者。我们使用 Cox 模型对时间进行了分析,以评估诊断时 GM 水平 (GM(0))、72 例 GM 值>或=2 的患者诊断后一周 GM 下降值、其他死亡率预测因素以及诊断后一周抗真菌药物使用情况与 6 周和 12 周死亡率之间的关系。整个队列的 6 周死亡率为 55%,GM 值>或=2 次测定的患者死亡率为 43%。GM(0) 每单位增加和 1 周 GM 每单位下降的危险比 (HR) 分别为 1.25(95%置信区间 [CI],1.01 至 1.54;P = 0.04)和 0.78(95% CI,0.63 至 0.96;P = 0.02),在调整了 IA 死亡率的其他预测因素后,这些值仍然稳定;在调整了抗真菌药物使用后,这些值仍然稳定,并且可以预测 12 周时的全因死亡率,调整后的 HR 值相似。我们得出结论,GM(0) 和 1 周 GM 下降的组合可预测 GPA 患者的全因死亡率,与其他死亡率传统危险因素和抗真菌药物暴露无关,支持 GM 下降作为未来抗真菌治疗试验的潜在替代终点。