Nocardia Infections in Hematopoietic Cell Transplant Recipients: A Multicenter International Retrospective Study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Author:

Averbuch Diana1,De Greef Julien2,Duréault Amelie3,Wendel Lotus4,Tridello Gloria5,Lebeaux David67,Mikulska Malgorzata8,Gil Lidia9,Knelange Nina4,Zuckerman Tsila10,Roussel Xavier11,Robin Christine12,Xhaard Alienor13,Aljurf Mahmoud14,Beguin Yves15,Le Bourgeois Amandine16,Botella-Garcia Carmen17,Khanna Nina18,Van Praet Jens19,Kröger Nicolaus20,Blijlevens Nicole21,Ducastelle Leprêtre Sophie22,Ho Aloysius23,Roos-Weil Damien24,Yeshurun Moshe2526,Lortholary Olivier2728,Fontanet Arnaud2930,de la Camara Rafael31,Coussement Julien3233,Maertens Johan34,Styczynski Jan35,Arat M,Blau I W,Bron D,Carlson K,Collin M,Cordonnier C,Ganser A,Gruhn B,Junghanss C,Marchand T,Martin S,Milone G A,Nagler A,Pagliuca S,Ram R,Ribera J M,de la Serna J,Stamouli M,Villate A,

Affiliation:

1. Pediatric Infectious Diseases, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel

2. Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium

3. Centre d’Infectiologie Necker Pasteur, Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Université Paris Descartes, Paris, France

4. European Society for Blood and Marrow Transplantation (EBMT) Data Office, Leiden, The Netherlands

5. Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

6. Université de Paris, Paris, France

7. Service de Microbiologie, Unité Mobile d’Infectiologie, Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France

8. Division of Infectious Diseases, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy

9. University of Medical Sciences, Poznan, Poland

10. Rambam Medical Center, Haifa, Israel

11. Hematology Department, University Hospital of Besançon, Besançon, France

12. Henri Mondor University Hospital, Creteil, France

13. Hematology-Transplantation, Hospital St-Louis, Paris Diderot University, Paris, France

14. King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

15. Centre Hospitalier Universitaire of Liège and University of Liège, Liège, Belgium

16. Centre Hospitalier Universitaire Nantes, Nantes, France

17. Centre Hospitalier Universitaire Bordeaux, Bordeaux, France

18. Division of Infectious Diseases and Hospital Epidemiology, University and University Hospital of Basel, Basel, Switzerland

19. Department of Nephrology and Infectious Diseases, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende, Brugge, Belgium

20. Department of Stem Cell Transplantation, University Medical Center, Hamburg, Germany

21. Radboud University Medical Center, Nijmegen, The Netherlands

22. Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France

23. Singapore General Hospital, Singapore

24. Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France

25. Institution of Hematology, Rabin Medical Center, Petah Tikva, Israel

26. Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel

27. Paris University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine IHU Imagine, Necker Enfants Malades University Hospital, Paris, France

28. National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, CNRS UMR 2000, Institut Pasteur, Paris, France

29. Institut Pasteur, Emerging Diseases Epidemiology Unit, Global Health Department, Paris, France

30. Pasteur-Cnam risques infectieux et émergents Unit, Conservatoire National des Arts et Métiers, Paris, France

31. Hospital de la Princesa, Madrid, Spain

32. Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia

33. National Centre for Infection in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia

34. Department of Hematology, Universitaire Ziekenhuizen Leuven, Leuven, Belgiumand

35. Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland

Abstract

Abstract Background Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population. Methods This retrospective international study reviewed nocardiosis episodes in HCT recipients (1/1/2000–31/12/2018; 135 transplant centers; 33 countries) and described their clinical, microbiological, radiological, and outcome characteristics. Results We identified 81 nocardiosis episodes in 74 allo- and 7 auto-HCT recipients. Nocardiosis occurred a median of 8 (IQR: 4–18) months post-HCT. The most frequently involved organs were lungs (70/81; 86%) and brain (30/81; 37%); 29 (36%) patients were afebrile; 46/81 (57%) had disseminated infections. The most common lung imaging findings were consolidations (33/68; 49%) or nodules (32/68; 47%); brain imaging findings were multiple brain abscesses (19/30; 63%). Ten of 30 (33%) patients with brain involvement lacked neurological symptoms. Fourteen of 48 (29%) patients were bacteremic. Nocardia farcinica was the most common among molecularly identified species (27%; 12/44). Highest susceptibility rates were reported to linezolid (45/45; 100%), amikacin (56/57; 98%), trimethoprim-sulfamethoxazole (57/63; 90%), and imipenem (49/57; 86%). One-year and last follow-up (IQR: 4–42.5 months) all-cause mortality were 40% (32/81) and 52% (42/81), respectively. In the multivariable analysis, underlying disease not in complete remission (HR: 2.81; 95% CI: 1.32–5.95) and prior bacterial infection (HR: 3.42; 95% CI: 1.62–7.22) were associated with higher 1-year all-cause mortality. Conclusions Nocardiosis is a late post-HCT infection usually manifesting as a pulmonary disease with frequent dissemination, brain infection, and bacteremia. Brain imaging should be performed in HCT recipients with nocardiosis regardless of neurological symptoms. Overall mortality is high.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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