Brown Lottie, Tschiderer Lena, Alanio Alexandre, Barnes Rosemary A, Chen Sharon C-A, Cogliati Massimo, Cruciani Mario, Donnelly J Peter, Hagen Ferry, Halliday Catriona, Klingspor Lena, Lagrou Katrien, Melchers Willem, Millon Laurence, Morio Florent, Salvador Elena, Stroffolini Giacomo, Ruhnke Markus, Toepfer Stephanie, van Dijk Karin, Borman Andrew M, Buitrago María José, Gorton Rebecca, Löffller Jürgen, Rautemaa-Richardson Riina, Sendid Boualem, Willeit Peter, White P Lewis, Lackner Michaela
St George's Hospital, St George's NHS Foundation Trust, London, UK.
Institute of Infection and Immunity, City St George's University of London, London, UK.
EClinicalMedicine. 2025 Feb 22;81:103115. doi: 10.1016/j.eclinm.2025.103115. eCollection 2025 Mar.
This systematic review and meta-analysis aimed to examine the performance of polymerase chain reaction (PCR) assays for diagnosing mucormycosis.
A standardised search was conducted from conception to December 3rd 2024 using PubMed, Embase, Global Health, and Cochrane library. Original studies that used PCR-based methods on any human specimen to diagnose mucormycosis were analysed for eligibility. Using a bivariate meta-analysis, the diagnostic performance of PCR was examined against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group Education and Research Consortium 2020 (EORTC-MSGERC) definitions of proven and probable invasive mould disease, which was modified to include all patients at risk of mucormycosis. The study protocol was registered on the PROSPERO database (CRD42023478667).
Of 4855 articles, a total of 30 met inclusion criteria, including 5920 PCR reactions on 5147 non-duplicate specimens from 819 cases of proven/probable mucormycosis and 4266 patients who did not meet the EORTC-MSGERC 2020 criteria. According to specimen type, sensitivity of PCR varied (p < 0.001) whereas specificity was similar (p = 0.662). Bronchoalveolar lavage fluid offered the highest sensitivity of 97.5% (95% CI 83.7-99.7%), specificity of 95.8% (95% CI 89.6-98.4%), positive likelihood ratio (LR+) of 23.5, and negative likelihood ratio (LR-) of 0.03. Tissue provided sensitivity of 86.4% (95% CI 78.9-91.5%), specificity of 90.6% (95% CI 78.1-96.3%), LR+ of 9.2, and LR- of 0.15. Blood provided reduced sensitivity of 81.6% (95% CI 70.1-89.4%), specificity of 95.5% (95% CI 87.4-98.5%), DOR of 95, LR+ of 18.3, and LR- of 0.19. Formalin-fixed paraffin-embedded specimens yielded the lowest sensitivity of 73.0% (95% CI 61.0-82.3%), highest specificity of 96.4% (CI 95% 87.5-99.0%), LR+ of 20.2, and LR- of 0.28. The covariates best explaining heterogeneity of the overall analysis were specimen type, study design (cohort case-control) and disease prevalence while patient population (COVID-19 other) and PCR (conventional quantitative) had less impact on heterogeneity.
This meta-analysis confirms the high performance of PCR for diagnosing mucormycosis and supports the instatement of PCR detection of free-DNA in blood, BALF and tissue into future updated definitions and diagnostic guidelines for mucormycosis.
None.
本系统评价和荟萃分析旨在评估聚合酶链反应（PCR）检测在诊断毛霉病中的性能。
从研究开始至2024年12月3日，使用PubMed、Embase、Global Health和Cochrane图书馆进行标准化检索。对使用基于PCR的方法检测任何人体标本以诊断毛霉病的原始研究进行纳入资格分析。采用双变量荟萃分析，根据欧洲癌症研究与治疗组织-真菌病研究组教育与研究联盟2020年（EORTC-MSGERC）对确诊和疑似侵袭性霉菌病的定义，对PCR的诊断性能进行评估，该定义经修改后纳入了所有有毛霉病风险的患者。研究方案已在PROSPERO数据库（CRD42023478667）中注册。
在4855篇文章中，共有30篇符合纳入标准，包括对819例确诊/疑似毛霉病患者的5147份非重复标本进行的5920次PCR反应，以及4266例不符合EORTC-MSGERC 2020标准的患者。根据标本类型，PCR的敏感性有所不同（p<0.001），而特异性相似（p=0.662）。支气管肺泡灌洗液的敏感性最高，为97.5%（95%CI 83.7-99.7%），特异性为95.8%（95%CI 89.6-98.4%），阳性似然比（LR+）为23.5，阴性似然比（LR-）为0.03。组织的敏感性为86.4%（95%CI 78.9-91.5%），特异性为90.6%（95%CI 78.1-96.3%），LR+为9.2，LR-为0.15。血液的敏感性降低，为81.6%（95%CI 70.1-89.4%），特异性为95.5%（95%CI 87.4-98.5%），诊断比值比（DOR）为95，LR+为18.3，LR-为0.19。福尔马林固定石蜡包埋标本的敏感性最低，为73.0%（95%CI 61.0-82.3%），特异性最高，为96.4%（CI 95% 87.5-99.0%），LR+为20.2，LR-为0.28。对总体分析异质性解释效果最佳的协变量是标本类型、研究设计（队列研究 vs 病例对照研究）和疾病患病率，而患者人群（新冠患者 vs 其他患者）和PCR类型（传统PCR vs 定量PCR）对异质性的影响较小。
本荟萃分析证实了PCR在诊断毛霉病方面的高性能，并支持将血液、支气管肺泡灌洗液和组织中游离DNA的PCR检测纳入未来更新的毛霉病定义和诊断指南。
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