通过对血浆中微生物无细胞 DNA 的下一代测序进行液体活检测试，以诊断造血细胞移植受者肺炎相关侵袭性霉菌感染。
Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma.
机构信息
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
University of Washington, Seattle, Washington, USA.
出版信息
Clin Infect Dis. 2021 Dec 6;73(11):e3876-e3883. doi: 10.1093/cid/ciaa1639.
BACKGROUND
Noninvasive diagnostic options are limited for invasive mold infections (IMIs). We evaluated the performance of a plasma microbial cell-free DNA sequencing (mcfDNA-Seq) test for diagnosing pulmonary IMI after hematopoietic cell transplant (HCT).
METHODS
We retrospectively assessed the diagnostic performance of plasma mcfDNA-Seq next-generation sequencing in 114 HCT recipients with pneumonia after HCT who had stored plasma obtained within 14 days of diagnosis of proven/probable Aspergillus IMI (n = 51), proven/probable non-Aspergillus IMI (n = 24), possible IMI (n = 20), and non-IMI controls (n = 19). Sequences were aligned to a database including >400 fungi. Organisms above a fixed significance threshold were reported.
RESULTS
Among 75 patients with proven/probable pulmonary IMI, mcfDNA-Seq detected ≥1 pathogenic mold in 38 patients (sensitivity, 51% [95% confidence interval {CI}, 39%-62%]). When restricted to samples obtained within 3 days of diagnosis, sensitivity increased to 61%. McfDNA-Seq had higher sensitivity for proven/probable non-Aspergillus IMI (sensitivity, 79% [95% CI, 56%-93%]) compared with Aspergillus IMI (sensitivity, 31% [95% CI, 19%-46%]). McfDNA-Seq also identified non-Aspergillus molds in an additional 7 patients in the Aspergillus subgroup and Aspergillus in 1 patient with possible IMI. Among 19 non-IMI pneumonia controls, mcfDNA-Seq was negative in all samples, suggesting a high specificity (95% CI, 82%-100%) and up to 100% positive predictive value (PPV) with estimated negative predictive values (NPVs) of 81%-99%. The mcfDNA-Seq assay was complementary to serum galactomannan index testing; in combination, they were positive in 84% of individuals with proven/probable pulmonary IMI.
CONCLUSIONS
Noninvasive mcfDNA-Seq had moderate sensitivity and high specificity, NPV, and PPV for pulmonary IMI after HCT, particularly for non-Aspergillus species.
背景
对于侵袭性霉菌感染（IMI），非侵入性诊断选择有限。我们评估了血浆微生物无细胞游离 DNA 测序（mcfDNA-Seq）检测在造血细胞移植（HCT）后患有肺炎的患者中用于诊断肺 IMI 的性能。
方法
我们回顾性评估了 114 例 HCT 受者的血浆 mcfDNA-Seq 下一代测序的诊断性能，这些受者在确诊/可能的曲霉菌 IMI（n = 51）、确诊/可能的非曲霉菌 IMI（n = 24）、可能的 IMI（n = 20）和非 IMI 对照组（n = 19）后 HCT 诊断为肺炎的 14 天内获得了血浆。序列与包括> 400 种真菌的数据库进行了比对。超过固定显著阈值的生物体被报告。
结果
在 75 例确诊/可能患有肺 IMI 的患者中，mcfDNA-Seq 在 38 例患者中检测到≥1 种致病性霉菌（敏感性，51%[95%置信区间{CI}，39%-62%]）。当限制在诊断后 3 天内获得的样本时，敏感性增加到 61%。mcfDNA-Seq 对确诊/可能的非曲霉菌 IMI 的敏感性更高（敏感性，79%[95%CI，56%-93%]），而曲霉菌 IMI 的敏感性为 31%（95%CI，19%-46%）。mcfDNA-Seq 还在曲霉菌亚组的另外 7 例患者中鉴定了非曲霉菌霉菌，并在 1 例可能患有 IMI 的患者中鉴定了曲霉菌。在 19 例非 IMI 肺炎对照组中，所有样本的 mcfDNA-Seq 均为阴性，提示高特异性（95%CI，82%-100%）和高达 100%的阳性预测值（PPV），估计阴性预测值（NPV）为 81%-99%。mcfDNA-Seq 检测与血清半乳甘露聚糖指数检测互补；联合使用时，在 84%的确诊/可能患有肺 IMI 的个体中呈阳性。
结论
非侵入性 mcfDNA-Seq 对 HCT 后肺 IMI 具有中等的敏感性和特异性、NPV 和 PPV，尤其是对非曲霉菌种。
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