The diagnosis of mucormycosis by PCR in patients at risk: a systematic review and meta-analysis

被引:0
作者
Brown, Lottie [1 ,2 ]
Tschiderer, Lena [3 ]
Alanio, Alexandre [4 ,5 ]
Barnes, Rosemary A. [6 ,25 ]
Chen, Sharon C-A [7 ,8 ]
Cogliati, Massimo [9 ]
Cruciani, Mario [10 ]
Donnelly, J. Peter [11 ]
Hagen, Ferry [12 ,13 ,14 ]
Halliday, Catriona [15 ]
Klingspor, Lena [16 ]
Lagrou, Katrien [17 ,18 ]
Melchers, Willem [19 ]
Millon, Laurence [20 ,21 ]
Morio, Florent [22 ]
Salvador, Elena [23 ]
Stroffolini, Giacomo [23 ]
Ruhnke, Markus [24 ]
Toepfer, Stephanie [25 ]
van Dijk, Karin [26 ]
Borman, Andrew M. [27 ,28 ]
Buitrago, Maria Jose [29 ,30 ]
Gorton, Rebecca [31 ]
Loeffller, Juergen [32 ]
Rautemaa-Richardson, Riina [33 ,34 ,35 ]
Sendid, Boualem [36 ]
Willeit, Peter [3 ,37 ,38 ]
White, P. Lewis [39 ,40 ]
Lacknerx, Michaela [25 ]
机构
[1] St Georges NHS Fdn Trust, St Georges Hosp, London, England
[2] City St Georges Univ London, Inst Infect & Immun, London, England
[3] Med Univ Innsbruck, Inst Clin Epidemiol Publ Hlth Hlth Econ Med Stat &, Innsbruck, Austria
[4] Univ Paris Cite, Inst Pasteur, Natl Reference Ctr Invas Mycoses & Antifungals, Mycol Dept,Translat Mycol Res Grp, F-75015 Paris, France
[5] Hop St Louis, AP HP, Lab Parasitol Mycol, F-75010 Paris, France
[6] Cardiff Univ, Sch Med, Cardiff, Wales
[7] Westmead Hosp, Inst Clin Pathol & Med Res, New South Wales Hlth Pathol, Ctr Infect Dis & Microbiol Lab Serv, Sydney, NSW, Australia
[8] Univ Sydney, Sydney, Australia
[9] Univ Milan, Dept Biomed Sci Hlth, Milan, Italy
[10] Working Grp Int Soc Human & Anim Mycol, Fungal PCR Initiat, Verona, Italy
[11] De Hoefkamp 1096, NL-6545 MD Nijmegen, Netherlands
[12] Westerdijk Fungal Biodivers Inst, Utrecht, Netherlands
[13] Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, Amsterdam, Netherlands
[14] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands
[15] Westmead Hosp, Inst Clin Pathol & Med Res, Clin Mycol Reference Lab, Ctr Infect Dis & Microbiol Lab Serv,New South Wale, Westmead, NSW, Australia
[16] Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden
[17] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Lab Clin Microbiol, Leuven, Belgium
[18] Univ Hosp Leuven, Natl Reference Ctr Mycosis, Dept Lab Med, Leuven, Belgium
[19] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands
[20] Franche Comte Univ, Chronoenvironm UMR6249, CNRS, F-25000 Besancon, France
[21] Besancon Univ Hosp, Parasitol Mycol Dept, Besancon, France
[22] Nantes Univ, CHU Nantes, Cibles & Medicaments Infect & Immunite, IICiMed,UR1155, F-44000 Nantes, France
[23] IRCCS Sacro Cuore Don Calabria Hosp, Dept Infect Trop Dis & Microbiol, Via Don A Sempreboni 5, I-37024 Verona, Italy
[24] HELIOS Klinikum Aue, Neurol Klin, Aue, Germany
[25] Med Univ Innsbruck, Inst Hyg & Med Microbiol, Innsbruck, Austria
[26] Univ Amsterdam, Dept Med Microbiol & Infect Prevent, Locat AMC, Med Ctr, Amsterdam, Netherlands
[27] Southmead Hosp, UKHSA Mycol Reference Lab, Bristol, England
[28] Univ Exeter, MRC, Ctr Med Mycol, Exeter, England
[29] Inst Salud Carlos III, Mycol Reference Lab, Natl Ctr Microbiol, Madrid, Spain
[30] Inst Salud Carlos III, CIBERINFEC, ISCIII CIBER Enfermedades Infecciosas, Madrid, Spain
[31] Hlth Serv Labs, Dept Infect Sci, London, England
[32] Univ Klinikum Wurzburg, Med Klin 2, Lab WU4i, D-35392 Wurzburg, Germany
[33] Manchester Univ NHS Fdn Trust, Wythenshawe Hosp, Mycol Reference Ctr Manchester, Manchester, England
[34] Manchester Univ NHS Fdn Trust, Wythenshawe Hosp, Dept Infect Dis, Manchester, England
[35] Univ Manchester, Fac Biol Med & Hlth, Div Evolut Infect & Genom, Manchester, England
[36] Univ Lille, Inst Translat Res Inflammat, Inserm, INSERM U1285,CNRS UMR 8576,CHU Lille, F-59000 Lille, France
[37] Ignaz Semmelweis Inst, Interuniv Inst Infect Res, Vienna, Austria
[38] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England
[39] UHW, Publ Hlth Wales Mycol Reference Lab, Cardiff, Wales
[40] UHW, Cardiff Univ Ctr Trials Res, Cardiff, Wales
关键词
Mucorales; Mucormycosis; PCR; Fungal; Diagnosis; CHAIN-REACTION ASSAYS; HISTOPATHOLOGICAL ANALYSIS; RAPID DETECTION; TEST ACCURACY; IDENTIFICATION; PULMONARY; CULTURE; SAMPLES; TISSUE; BIOPSY;
D O I
10.1016/j.eclinm.2025.103115
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background This systematic review and meta-analysis aimed to examine the performance of polymerase chain reaction (PCR) assays for diagnosing mucormycosis. Methods 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). Findings 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 EORTCMSGERC 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 versus case-control) and disease prevalence while patient population (COVID-19 versus other) and PCR (conventional versus quantitative) had less impact on heterogeneity. Interpretation 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. Copyright Crown Copyright (c) 2025 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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页数:12
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