title: Detection of Circulating Mucorales DNA in Critically Ill Burn Patients: Preliminary Report of a Screening Strategy for Early Diagnosis and Treatment.
abstract: BACKGROUND
  Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. We describe the detection of circulating Mucorales DNA (cmDNA) for the early diagnosis of IWM in those patients and report the potential value of detecting cmDNA for treatment guidance.
  
  
  METHODS
  Severely ill burn patients admitted to our tertiary referral center between October 2013 and February 2016 were included. Retrospective plasma samples were tested for the presence of cmDNA by quantitative real-time polymerase chain reaction (qPCR). Patients were then prospectively screened twice a week, and liposomal amphotericin-B therapy initiated based on a positive qPCR. The primary endpoint was the time between cmDNA detection and standard diagnosis. Secondary endpoints were the time from cmDNA detection and treatment initiation and mortality.
  
  
  RESULTS
  Seventy-seven patients (418 samples) were included. The average age was 46 (28-60) years, abbreviated burn severity index was 8 (7-10), and simplified acute physiology score was 33 (23-46). The total body surface area was 33% (22%-52%). cmDNA was detected 11 (4.5-15) days before standard diagnosis. The in-hospital mortality was 62% for patients with IWM and 24% for those without (P = .03). The mortality due to IWM was 80% during period A and 33% during period B (P = .46).
  
  
  CONCLUSIONS
  This study suggests that the detection of cmDNA allows earlier diagnosis of IWM in severely ill burn patients and earlier initiation of treatment. Further studies are needed to confirm the impact of earlier treatment initiation on patient outcome.
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.|Université Paris Diderot, Sorbonne Paris Cité.|UMR 942, INSERM.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Legrand
authors.affiliation: Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Maud
authors.initials: M
authors.lastname: Gits-Muselli
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Louis
authors.initials: L
authors.lastname: Boutin
authors.affiliation: Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques.|CNRS URA3012.
authors.forename: Dea
authors.initials: D
authors.lastname: Garcia-Hermoso
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Véronique
authors.initials: V
authors.lastname: Maurel
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Sabri
authors.initials: S
authors.lastname: Soussi
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Mourad
authors.initials: M
authors.lastname: Benyamina
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Axelle
authors.initials: A
authors.lastname: Ferry
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Maïté
authors.initials: M
authors.lastname: Chaussard
authors.affiliation: Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Samia
authors.initials: S
authors.lastname: Hamane
authors.affiliation: Service de Maladies Infectieuses et Tropicales, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Blandine
authors.initials: B
authors.lastname: Denis
authors.affiliation: Pharmacie, Hôpital St-Louis, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris.
authors.forename: Sophie
authors.initials: S
authors.lastname: Touratier
authors.affiliation: Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guigue
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, CNRS, UMR 8204, Inserm, U1019, CHU Lille, Laboratoire de Parasitologie- Mycologie, Institut Pasteur de Lille.
authors.forename: Emilie
authors.initials: E
authors.lastname: Fréalle
authors.affiliation: CHU Lille, Centre de Traitement des Brûlés, Pôle d'Anesthésie-Réanimation, Lille.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Jeanne
authors.affiliation: Centre de traitement des brulés, Hopital d'instruction des Armées.
authors.forename: Jean-Vivien
authors.initials: JV
authors.lastname: Shaal
authors.affiliation: Service de Biologie médicale, Hopital d'instruction des Armées, Clamart.
authors.forename: Charles
authors.initials: C
authors.lastname: Soler
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité.|Service de chirurgie plastique, reconstructrice, esthétique et traitement chirurgical des brûlés, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Mimoun
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité.|Service de chirurgie plastique, reconstructrice, esthétique et traitement chirurgical des brûlés, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Chaouat
authors.affiliation: Service de Maladies Infectieuses et Tropicales, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lafaurie
authors.affiliation: Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.|Université Paris Diderot, Sorbonne Paris Cité.|UMR 942, INSERM.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité.|Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.|Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques.|CNRS URA3012.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bretagne
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité.|Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal.|Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques.|CNRS URA3012.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alanio
mesh_terms: D000328:Adult; D000368:Aged; D002056:Burns / Q000150:complications / Q000453:epidemiology / Q000382:microbiology*; D016638:Critical Illness; D004271:DNA, Fungal / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D009090:Mucorales / Q000235:genetics*; D009091:Mucormycosis / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D016533:Mycological Typing Techniques; D012189:Retrospective Studies
chemical_list: D004271:DNA, Fungal
keywords: DNA; early treatment; immunocompromised; invasive fungal infection; screening