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Evaluation of serum Mucorales PCR for the diagnosis of Mucormycoses: The MODIMUCOR prospective trial

Laurence Millon 1, 2 Denis Caillot 3 Ana Berceanu 4 Stéphane Bretagne 5, 6, 7, 8 Fanny Lanternier 5, 6, 8 Florent Morio 9, 10 Valérie Letscher-Bru 11 Frédéric Dalle 12, 13 Blandine Denis 14 Alexandre Alanio 5, 6, 7, 8 David Boutoille 15 Marie-Elisabeth Bougnoux 16, 17 Françoise Botterel 18, 19 Taieb Chouaki 20, 21 Amandine Charbonnier 22 Florence Ader Damien Dupont 23 Anne-Pauline Bellanger 1, 2 Steffi Rocchi 1, 2 Emeline Scherer 1, 2 Houssein Gbaguidi-Haore 2, 24 Raoul Herbrecht 25, 26 
18 Unité de Parasitologie-Mycologie [Créteil]
Département de Prévention, Diagnostic et Traitement des Infections [Créteil]
Abstract : Background Early diagnosis and prompt initiation of specific antifungal treatment is essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative PCR (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 species 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 four days (IQR, 0-9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, (-2)-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%CI [0·03-0·73], p = 0·02). Conclusion 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.
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Submitted on : Thursday, January 20, 2022 - 11:16:01 AM
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Laurence Millon, Denis Caillot, Ana Berceanu, Stéphane Bretagne, Fanny Lanternier, et al.. Evaluation of serum Mucorales PCR for the diagnosis of Mucormycoses: The MODIMUCOR prospective trial. Clinical Infectious Diseases, Oxford University Press (OUP), In press, ⟨10.1093/cid/ciab1066⟩. ⟨hal-03528144⟩

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