Matthieu Legrand1,2,3, Maud Gits-Muselli4, Louis Boutin1, Dea Garcia-Hermoso5,6, Véronique Maurel1, Sabri Soussi1, Mourad Benyamina1, Axelle Ferry1, Maïté Chaussard1, Samia Hamane4, Blandine Denis7, Sophie Touratier8, Nicolas Guigue4, Emilie Fréalle9, Mathieu Jeanne10, Jean-Vivien Shaal11, Charles Soler12, Maurice Mimoun2,13, Marc Chaouat2,13, Matthieu Lafaurie7, Alexandre Mebazaa1,2,3, Stéphane Bretagne2,4,5,6, Alexandre Alanio2,4,5,6. 1. Anesthesiology, Critical Care and Burn Unit, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal. 2. Université Paris Diderot, Sorbonne Paris Cité. 3. UMR 942, INSERM. 4. Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal. 5. Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques. 6. CNRS URA3012. 7. Service de Maladies Infectieuses et Tropicales, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal. 8. Pharmacie, Hôpital St-Louis, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris. 9. 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. 10. CHU Lille, Centre de Traitement des Brûlés, Pôle d'Anesthésie-Réanimation, Lille. 11. Centre de traitement des brulés, Hopital d'instruction des Armées. 12. Service de Biologie médicale, Hopital d'instruction des Armées, Clamart. 13. Service de chirurgie plastique, reconstructrice, esthétique et traitement chirurgical des brûlés, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France.
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.
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.
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Authors: Sean X Zhang; N Esther Babady; Kimberly E Hanson; Amanda T Harrington; Paige M K Larkin; Sixto M Leal; Paul M Luethy; Isabella W Martin; Preeti Pancholi; Gary W Procop; Stefan Riedel; Seyedmojtaba Seyedmousavi; Kaede V Sullivan; Thomas J Walsh; Shawn R Lockhart Journal: J Clin Microbiol Date: 2021-06-18 Impact factor: 5.948