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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
1 Service de parasitologie et mycologie [CHRU de Besançon]
2 LCE - Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249)
3 Service d'Hématologie Clinique (CHU de Dijon)
4 Service d'Hématologie [CHRU Besançon]
5 Mycologie moléculaire - Molecular Mycology
6 CNRMA - Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals
7 Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris]
8 UPC - Université Paris Cité
9 Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes)
10 IICiMed - Cibles et médicaments de l'infection, de l'immunité et du cancer
11 Laboratoire de parasitologie et mycologie médicale [CHU Strasbourg]
12 Laboratoire de parasitologie mycologie (CHU de Dijon)
13 PAM - Procédés Alimentaires et Microbiologiques [Dijon]
14 Service des Maladies Infectieuses et Tropicales [CHU Saint Louis]
15 Service des maladies infectieuses et tropicales [CHU Nantes]
16 Unité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris]
17 BPF - Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity
18 Unité de Parasitologie-Mycologie [Créteil]
Département de Prévention, Diagnostic et Traitement des Infections [Créteil]
19 DYNAMIC - Dynamic Microbiology - EA 7380
20 Laboratoire de parasitologie et de mycologie médicales [CHU Amiens]
21 AGIR - Agents infectieux, résistance et chimiothérapie - UR UPJV 4294
22 Laboratoire d'Hématologie [CHU Amiens]
23 Service de parasitologie et mycologie médicale [Hôpital de la Croix Rousse, Lyon]
24 Service d'Epidémiologie [CHRU Besançon]
25 ICANS - Institut de Cancérologie de Strasbourg Europe
26 IRFAC - Inserm U1113 - Interface de Recherche Fondamentale et Appliquée en Cancérologie
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.
Keywords : Mucorales quantitative PCR Mucormycosis circulating DNA molecular diagnosis
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Journal articles
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Contributor : Laurence Millon Connect in order to contact the contributor
Submitted on : Thursday, January 20, 2022 - 11:16:01 AM
Last modification on : Friday, May 20, 2022 - 9:06:42 AM
Long-term archiving on: : Thursday, April 21, 2022 - 6:47:49 PM

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UNIV-FCOMTE | UNIV-PARIS | FNCLCC | U-PICARDIE | PAM | SITE-ALSACE | INRAE | CHRONO-ENVIRONNEMENT | PASTEUR | UNIV-NANTES | UNIV-BOURGOGNE | HCL | AGIR-UPJV | CNRS | INSERM | LIB_UB | IICIMED | ENVA | UPEC-UPEM | UPEC | DYNAMIC

Citation

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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