Risk factors for Nocardia infection among allogeneic hematopoietic cell transplant recipients: A case-control study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation - 17/05/24

Doi : 10.1016/j.jinf.2024.106162

Julien De Greef ^a,^{^{1
JDG and DA contributed equally to this work (co-first authors).}}, Dina Averbuch ^b,^{^{1
JDG and DA contributed equally to this work (co-first authors).}}, Laura Tondeur ^c,^{^{2
LT and AD contributed equally to this work (co-second authors).}}, Amélie Duréault ^d,^{^{2
LT and AD contributed equally to this work (co-second authors).}}, Tsila Zuckerman ^e,^f, Xavier Roussel ^g, Christine Robin ^h, Alienor Xhaard ⁱ, Simona Pagliuca ^j, Yves Beguin ^k, Carmen Botella-Garcia ^l, Nina Khanna ^m, Amandine Le Bourgeois ⁿ, Jens Van Praet ^o, Aloysius Ho ^p, Nicolaus Kröger ^q, Sophie Ducastelle Leprêtre ^r, Damien Roos-Weil ^s, Mahmoud Aljurf ^t, Nicole Blijlevens ^u, Igor Wolfgang Blau ^v, Kristina Carlson ^w, Matthew Collin ^x, Arnold Ganser ^y, Alban Villate ^z, Johannes Lakner ^aa, Sonja Martin ^ab, Arnon Nagler ^ac, Ron Ram ^ad, Anna Torrent ^ae, Maria Stamouli ^af, Malgorzata Mikulska ^ag,^ah, Lidia Gil ^ai, Lotus Wendel ^ai, Gloria Tridello ^ai, Nina Knelange ^ai, Rafael de la Camara ^aj,^ak, Olivier Lortholary ^d, Arnaud Fontanet ^c,^al, Jan Styczynski ^am, Johan Maertens ^an, Julien Coussement ^ao,^ap,^⁎,^{^{3
JC and DL contributed equally to this work (co-senior authors).}} , David Lebeaux ^aq,^ar,^{^{3
JC and DL contributed equally to this work (co-senior authors).}}
^a Department of Internal Medicine and Infectious Diseases, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium
^b Pediatric Infectious Diseases, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
^c Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris Cité, 75015 Paris, France
^d Centre d′Infectiologie Necker Pasteur, Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Université Paris Descartes, Paris, France
^e Rambam Health Care Campus, Haifa, Israel
^f Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
^g Department of Hematology, University of Franche-Comte, INSERM UMR1098, Besançon University Hospital, Besançon, France
^h Department of Hematology, Henri Mondor University Hospital, Creteil, France
ⁱ Hematology-Transplantation, Hospital St-Louis, Paris Diderot University, Paris, France
^j Hematology Department, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
^k Centre Hospitalier Universitaire of Liège and University of Liège, Liège, Belgium
^l Centre Hospitalier Universitaire Bordeaux, Bordeaux, France
^m Division of Infectious Diseases and Hospital Epidemiology, University and University Hospital of Basel, Basel, Switzerland
ⁿ Centre Hospitalier Universitaire Nantes, Nantes, France
^o Department of Nephrology and Infectious Diseases, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende, Brugge, Belgium
^p Singapore General Hospital, Singapore
^q Department of Stem Cell Transplantation, University Medical Center, Hamburg, Germany
^r Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
^s Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
^t King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
^u Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands
^v Campus Virchow Klinikum CVK, Berlin, Germany
^w Dept of Haematology, University Hospital, Uppsala, Sweden
^x Nordern Centre for Bone Marrow Transplantation Freeman Hospital - Adult HSCT Unit, Newcastle, United Kingdom
^y Department of Hematology Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
^z Service d′hématologie et thérapie cellulaire, Centre Hospitalier Universitaire de Tours, Université de Tours, Tours, France
^aa Medical Clinic III, University Medical Center, Rostock, Germany
^ab Robert-Bosch-Krankenhaus, Stuttgart, Germany
^ac Chaim Sheba Medical Center, Tel Hashomer, Israel
^ad Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
^ae ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain
^af Attikon University General Hospital, Athens, Greece
^ag Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy
^ah IRCCS Ospedale Policlinico San Martino, Genoa, Italy
^ai European Society for Blood and Marrow Transplantation (EBMT), Leiden Study Unit, Leiden, the Netherlands
^aj Hospital de la Princesa, Madrid, Spain
^ak Infectious Diseases Working Party, EBMT, Spain
^al Unité PACRI, Conservatoire National des Arts et Métiers, 75003 Paris, France
^am Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland
^an Department of Hematology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium
^ao Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
^ap Service de Maladies Infectieuses et Tropicales, Centre Hospitalier universitaire de Guadeloupe, Les Abymes, Guadeloupe, France
^aq Institut Pasteur, Université Paris Cité, CNRS UMR 6047, Genetics of Biofilms Laboratory, 75015 Paris, France
^ar Département de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Saint-Louis, Lariboisière, F-75010 Paris, France

^⁎Corresponding author at: Service de Maladies Infectieuses et Tropicales, Centre Hospitalier universitaire de Guadeloupe, Les Abymes, Guadeloupe, France.Service de Maladies Infectieuses et Tropicales, Centre Hospitalier universitaire de GuadeloupeLes AbymesGuadeloupeFrance

Summary

Objectives

Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence.

Methods

We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests.

Results

Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5–18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6–62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3–34.7), male sex (aOR 8.1, 95 % CI: 2.1–31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2–28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2–15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1–0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001).

Conclusions

We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.

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Highlights

•	Nocardiosis after allogeneic hematopoietic cell transplantation is a rare but severe infection.
•	Tacrolimus use, lymphopenia, recent corticosteroids, recent CMV infection and male sex were associated with Nocardiosis.
•	Trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.
•	Patients with nocardiosis had a significantly increased risk of death compared to controls.

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Keywords : Nocardiosis, Hematopoietic stem cell transplantation, HSCT

Plan

Introduction

Methods

Study design and setting

Characteristics of cases and controls

Risk factors for nocardiosis

Survival analysis

Discussion

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Vol 88 - N° 6

Article 106162- juin 2024 Retour au numéro

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Risk factors for Nocardia infection among allogeneic hematopoietic cell transplant recipients: A case-control study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation - 17/05/24

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