Assessment of the clinical utility of serial β-D-glucan concentrations in patients with persistent neutropenic fever

Assessment of the clinical utility of serial β-D-glucan concentrations in patients with persistent neutropenic fever
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DOI:
10.1099/jmm.0.47479-0
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发表时间:
2008-03-01
影响因子:
3
通讯作者:
Klingspor, Lena
Klingspor, Lena
中科院分区:
医学3区
文献类型:
--
作者:
Ellis, Michael;Al-Ramadi, Basel;Klingspor, Lena

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在100例接受化疗的血液恶性肿瘤患者中研究了Fungitell检测试剂盒的性能,这些患者发生了无反应性血小板减少性发热(AUNF)。与42名未发生侵袭性真菌感染的患者相比,38名发生侵袭性真菌感染(IFI)的患者的血清β-D-葡聚糖(BG)浓度在AUNF的第一天以及随后的每隔一天至第10天显著升高。IFI患者BG的平均值和中位数分别为171.9 +/- 29.6和95.8 pg/ml(-1),而单纯AUNF患者BG的平均值和中位数分别为64.4 +/- 17.1和32.9 pg/ml(-1(P= 2个连续浓度>= 80 pg/ml(-1))(“阳性”测试)被发现是诊断的最佳总体选择,准确性为81.3,灵敏度为86.8%,阳性预测值为76.7%,阴性预测值为86.5%在IFI患者中,78%的患者在临床诊断时或之前出现阳性检测-这发生在IFI诊断前1.25(-14至+14)天的平均值(范围)。通过从中性粒细胞减少症的第一天而不是从AUNF的第一天开始采血,50%的后续IFI患者将在5天前被识别。将采样频率从隔日增加到每日并没有进一步改善IFI诊断的早期时机。与血糖水平较低但无明显IFI的患者相比,血糖水平持续高且无明显IFI的患者发生严重肠上皮细胞损伤或粘膜炎的比例更高(P=0.002)。如果根据初始BG检测结果改变抗真菌治疗,则30%的患者不适合停药,并会延迟确定的抗真菌治疗。虽然研究的患者队列的结果非常有用,但测试的性能存在患者间的差异。因此,有必要采用整体诊断方法来最佳地解释测试结果。未来的研究应进一步详细说明这一点,以及经验性抗真菌药物使用和患者结局的影响。
The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum beta-D-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9 +/- 29.6 and 95.8 pg ml(-1), respectively, for patients with IFI and 64.4 +/- 17.1 and 32.9 pg ml(-1) for patients with only AUNF (P= 2 sequential concentrations of >= 80 pg ml(-1) ('positive' test) was found to give the best overall option for diagnosis, with an accuracy of 81.3 sensitivity of 86.8 %, positive predictive value of 76.7 % and negative predictive value of 86.5 Of the patients with an IFI, 78 % developed a positive test at or before the clinical diagnosis was made - this occurred at a mean (range) of 1.25 (-14 to + 14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50 % of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30 % of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.