Lieu Anthony, Zimmet Alex N, Pozdol Joseph, Kushner Lauren E, Ho Dora, Banaei Niaz
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA.
Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia, Canada.
Clin Infect Dis. 2025 Jun 4;80(5):1095-1102. doi: 10.1093/cid/ciaf021.
Mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) is a promising noninvasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear.
This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection. Mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium species. Invasive procedures included tissue biopsy and bronchoscopy. The primary endpoint was the concordance of mold plasma cfDNA PCR results with results of conventional fungal tests performed on tissue and bronchoalveolar lavage fluid.
Five hundred and six patients with mold plasma cfDNA PCR resulting ahead of invasive specimen (123 tissue and 426 bronchoalveolar lavage fluid) results were included, and 437 (86.4%) were immunocompromised. After adjudicating discordant results based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium definitions for IMD, mold plasma cfDNA PCR and invasive test results were 88.5% (448/506) concordant. In proven cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results occurred in patients with fungal sinusitis (8) and limb infection (3). Nonhematologic malignancy and nonneutropenic state were statistically associated with negative mold plasma cfDNA PCR in patients with proven or probable IMD.
Noninvasive mold plasma cfDNA PCR results were highly concordant with invasive specimen fungal test results, indicating risk-prone invasive specimen collection can be safely curtailed in immunocompromised patients with suspected IMD.
霉菌血浆游离DNA（cfDNA）聚合酶链反应（PCR）是一种很有前景的非侵入性诊断方法，用于免疫功能低下患者侵袭性霉菌病（IMD）的早期诊断。尽管霉菌cfDNA PCR已被证明具有高度准确性，但在血浆cfDNA检测后，通过侵入性操作收集标本进行传统真菌诊断的价值仍不明确。
这项回顾性单中心队列研究纳入了在侵入性标本采集前7天或采集后2天进行霉菌血浆cfDNA PCR检测的患者。霉菌PCR检测曲霉菌属、毛霉目病原体、镰刀菌属和足放线病菌属。侵入性操作包括组织活检和支气管镜检查。主要终点是霉菌血浆cfDNA PCR结果与对组织和支气管肺泡灌洗液进行的传统真菌检测结果的一致性。
纳入了506例霉菌血浆cfDNA PCR结果先于侵入性标本（123份组织和426份支气管肺泡灌洗液）结果的患者，其中437例（86.4%）免疫功能低下。根据欧洲癌症研究与治疗组织和真菌病研究组教育与研究联盟对IMD的定义对不一致结果进行判定后，霉菌血浆cfDNA PCR与侵入性检测结果的一致性为88.5%（448/506）。在确诊病例中，64.7%（11/17）的霉菌血浆cfDNA PCR阴性结果出现在真菌性鼻窦炎（8例）和肢体感染（3例）患者中。在确诊或可能患有IMD的患者中，非血液系统恶性肿瘤和非中性粒细胞减少状态与霉菌血浆cfDNA PCR阴性在统计学上相关。
非侵入性霉菌血浆cfDNA PCR结果与侵入性标本真菌检测结果高度一致，表明在疑似IMD的免疫功能低下患者中，可以安全地减少有风险的侵入性标本采集。
