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; R. Herbrecht; F. Grenouillet; F. Morio; Alexandre Alanio; V. Letscher-Bru; S. Cassaing; T. Chouaki; C. Kauffmann-Lacroix; P. Poirier; D. Toubas; O. Augereau; S. Rocchi; D. Garcia-Hermoso; S. Bretagne; French Mycosis Study Group

doi:10.1016/j.cmi.2015.12.006

Journal articles

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 - CNRS - UFC (UMR 6249)

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 Poitiers - Centre hospitalier universitaire de Poitiers

16 CHU - CHU Gabriel Montpied

17 MEDyC - Matrice extracellulaire et dynamique cellulaire - UMR 7369

18 CHU 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

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Human health and pathology / Infectious diseases

Life Sciences [q-bio] / Microbiology and Parasitology / Mycology

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https://hal-pasteur.archives-ouvertes.fr/pasteur-01405208
Contributor : Floran Bidault <>
Submitted on : Tuesday, November 29, 2016 - 4:13:55 PM
Last modification on : Sunday, October 25, 2020 - 7:06:48 AM

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, Elsevier for the European Society of Clinical Microbiology and Infectious Diseases, 2016, 22 (9), pp.810.e1--810.e8. ⟨10.1016/j.cmi.2015.12.006⟩. ⟨pasteur-01405208⟩

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)

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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)

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