Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial . (5th January 2022)

• Record Type: Journal Article
• Authors: Millon, Laurence; Caillot, Denis; Berceanu, Ana; Bretagne, Stéphane; Lanternier, Fanny; Morio, Florent; Letscher-Bru, Valérie; Dalle, Frédéric; Denis, Blandine; Alanio, Alexandre; Boutoille, David; Bougnoux, Marie Elisabeth; Botterel, Françoise; Chouaki, Taieb; Charbonnier, Amandine; Ader, Florence; Dupont, Damien; Bellanger, Anne Pauline; Rocchi, Steffi; Scherer, Emeline; Gbaguidi-Haore, Houssein; Herbrecht, Raoul
• Is Part Of: Clinical infectious diseases. Volume 75:Number 5(2022)
• Page Start: 777
• Page End: 785
• Publication Date: 2022-01-05
• Subjects: mucormycosis -- molecular diagnosis -- Mucorales quantitative PCR -- circulating DNA; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciab1066
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the early diagnosis and follow-up of mucormycosis. Methods: We prospectively enrolled 232 patients with suspicion of invasive mold disease, evaluated using standard imaging and mycological procedures. Thirteen additional patients with proven or probable mucormycosis were included to analyze DNA load kinetics. Serum samples were collected twice-a-week for Mucorales qPCR tests targeting the Mucorales genera Lichtheimia, Rhizomucor, and Mucor/Rhizopus . Results: The sensitivity was 85.2%, specificity 89.8%, and positive and negative likelihood ratios 8.3 and 0.17, respectively in this prospective study. The first Mucorales qPCR-positive serum was observed a median of 4 days (interquartile range [IQR], 0–9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, −2 to 6) before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate (adjusted hazard ratio = 0·15, 95% confidence interval [.03–.73], P = .02). Conclusions: Our study argues for the inclusion of qPCR for the detection of circulating Mucorales DNA for mucormycosis diagnosis and follow-up after treatment initiation. Positive results should be added to the criteria for the consensual definitions from the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), as already done for Aspergillus PCR. Abstract : This prospective multicenter study confirms the satisfactory performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the diagnosis of mucormycosis and argues for addition of this new tool in clinical settings and European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) consensual definitions to improve the management of mucormycosis.