Department of Medicine and Pathology, University of Utah, Salt Lake City, Utah, United States of America.
PLoS One. 2012;7(8):e42282. doi: 10.1371/journal.pone.0042282. Epub 2012 Aug 6.
Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.
Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.
Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.
BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.
Clinical Trials.gov NCT00672841.
侵袭性念珠菌病（IC）是一种毁灭性的疾病。虽然及时的抗真菌治疗可以改善预后，但基于发热而进行的经验性治疗对临床结果影响甚微。β-D-葡聚糖（BDG）是一种可在早期侵袭性真菌感染（IFI）患者血清中检测到的真菌细胞壁成分。我们评估了 BDG 监测作为指导高危重症监护病房（ICU）患者预防性抗真菌治疗的作用。
纳入 ICU 住院时间≥3 天且预计至少还需要 2 天强化治疗的患者。将受试者按 3：1 的比例随机分配至接受每周两次 BDG 监测，若检测结果阳性则进行预防性安尼芬净治疗，或根据医生的经验选择进行经验性抗真菌治疗。
在 2.5 年的研究期间，共纳入 64 例患者，其中有 1 例确诊和 5 例可能的 IC 病例。与无 IFI 的患者相比，确诊/可能的 IC 患者的 BDG 水平更高（117pg/ml 比 28pg/ml；p＜0.001）。最佳检测性能需要 2 次连续 BDG 检测结果≥80pg/ml 才能定义为阳性检测（敏感性 100%，特异性 75%，阳性预测值 30%，阴性预测值 100%）。共有 21 例患者接受了预防性和 5 例经验性全身抗真菌治疗。接受预防性抗真菌治疗对 BDG 浓度有显著影响（p＜0.001）。预防性使用安尼芬净安全且通常耐受良好，预后良好。
BDG 监测可能有助于识别发生 IFI 风险最高的 ICU 患者，并监测治疗反应。基于真菌生物标志物的预防策略值得进一步研究。
ClinicalTrials.gov NCT00672841。
