Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF)

L. Millon 1, 2 R. Herbrecht 3 F. Grenouillet 2, 1 F. Morio 4, 5 Alexandre Alanio 6, 7, 8, 9 V. Letscher-Bru 10, 11 S. Cassaing 12 T. Chouaki 13, 14 C. Kauffmann-Lacroix 15 P. Poirier 16 D. Toubas 17, 18 O. Augereau 19 S. Rocchi 1 D. Garcia-Hermoso 6, 7 S. Bretagne 9, 6, 7, 8 French Mycosis Study Group
1 LCE - Laboratoire Chrono-environnement
2 service de parasito-mycologie CHU Besancon
service de parasitologie mycologie CHU Jean Minjoz BESANCON
3 Service d’Oncologie et d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
4 IICiMed - EA 1155
5 CHU Nantes - Centre hospitalier universitaire de Nantes
6 Mycologie moléculaire
7 CNRMA - Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire
8 UPD7 - Université Paris Diderot - Paris 7
9 Hôpital Saint-Louis
10 Les Hôpitaux Universitaires de Strasbourg (HUS)
11 Institut de Parasitologie et de Pathologie Tropicale
12 Service de Parasitologie-Mycologie [Toulouse]
13 UPJV - Université de Picardie Jules Verne
14 CHU Amiens-Picardie
15 CHU de Poitiers
16 CHU - CHU Gabriel Montpied
17 MEDyC - Matrice extracellulaire et dynamique cellulaire - UMR 7369
18 CHU de Reims - Centre Hospitalier Universitaire de Reims
19 CHR - Centre Hospitalier Régional d'Orléans
Abstract : The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p \textless10(-6)). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.
Keywords : Mucormycosis Diagnosis monitoring Mucorales Quantitative PCR
Type de document :
Article dans une revue
Clinical Microbiology and Infection, Wiley, 2016, 22 (9), pp.810.e1--810.e8. 〈10.1016/j.cmi.2015.12.006〉
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01405208
Contributeur : Floran Bidault <>
Soumis le : mardi 29 novembre 2016 - 16:13:55
Dernière modification le : jeudi 5 avril 2018 - 10:37:00

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PASTEUR | UNIV-FCOMTE | UNIV-TLSE3 | UNIV-NANTES | USPC | CHRONO-ENVIRONNEMENT | URCA | MEDYC | CAPSANTE

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L. Millon, R. Herbrecht, F. Grenouillet, F. Morio, Alexandre Alanio, et al.. Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF). Clinical Microbiology and Infection, Wiley, 2016, 22 (9), pp.810.e1--810.e8. 〈10.1016/j.cmi.2015.12.006〉. 〈pasteur-01405208〉

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