Non-culture based diagnostic tests for detection of bacterial infections in hematology patients with febrile neutropenia: A review by the European Conference on Infections in Leukemia (ECIL-10) - 01/07/26

Doi : 10.1016/j.retram.2026.103600

Dionysios Neofytos ^1,^⁎ , Patricia Muñoz ^2,^3,⁴, Dina Averbuch ^5,⁶, Malgorzata Mikulska ^7,⁸, Yuri Vanbiervliet ⁹, Francesco Baccelli ^10,¹¹, Carolina Garcia Vidal ^4,¹², Manuela Aguilar-Guisado ^4,¹³, Nicole Blijlevens ¹⁴, Murat Akova ¹⁵, Thierry Calandra ¹⁶, Catherine Cordonnier ¹⁷

¹ Division of Infectious Disease, Transplant Infectious Disease Unit, University Hospital of Geneva, Geneva, Switzerland

² Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

³ Faculty of Medicine, Universidad Complutense de Madrid, Spain

⁴ CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain

⁵ Faculty of Medicine, Hebrew University of Jerusalem; Pediatric Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel

⁶ Chair Infectious Diseases Working Party EBMT

⁷ Infectious Diseases, Disease Department, Hospital Clinic of Health Sciences (DISSAL), University of Genova, Genova, Italy

⁸ IRCCS Ospedale Policlinico San Martino, Genova, Italy

⁹ Department Microbiology, Immunology and Transplantation, KU Leuven, Department of Haematology UZ Leuven, Leuven, Belgium

¹⁰ Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

¹¹ Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy

¹² Infectious Diseases Department, Hospital Clinic of Barcelona – IDIBAPS, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain

¹³ Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Instituto de Biomedicina de Sevilla (IBiS), Virgen del Rocío University Hospital /CSIC/University of Seville, Seville, Spain

¹⁴ Department of Hematology, Radboud university medical centre, Nijmegen, The Netherlands

¹⁵ Hacettepe University School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara, Türkiye; International Immunocompromised Host Society (ICHS)

¹⁶ Service of Immunology and Allergy, Department of Medicine and Department of Laboratory Medicine and Pathology, Center for Human Immunology Lausanne, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

¹⁷ Hematology Department, University Paris-Est Créteil, Creteil, France

^⁎ Corresponding author. Dionysios Neofytos

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Abstract

Background

Limited data are available on the performance of non-culture-based diagnostics in hematology patients with febrile neutropenia (FN).

Methods

The European Conference on Infections in Leukaemia (ECIL) 10 group performed a review (2011-2024) on the performance of available in Europe non-culture-based diagnostic methods on blood samples in hematology patients with FN, focusing on bacterial infections. The following tests were included: direct matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), multiplex/specific polymerase chain reaction (PCR), T2-magnetic resonance (T2MR), and metagenomic next generation sequencing (mNGS). A list of 6 predefined pertinent questions was assessed for the performance of each test.

Results

For MALDI-TOF-MS, 4/16 (25%) articles were retained, including 475 hematology patients (98 with FN), with sensitivity ranging from 63 to 92.6%. For multiplex-PCR, 8/293 (2.7%) articles were retained, including 509 hematology patients (209 with FN), with a sensitivity of 80.5% and 100% (2 studies) and one study reporting a specificity of 88.5%. For T2MR, 1/18 (5.6%) article was retained including 648 hematology patients (309 with FN) and sensitivity and specificity of 84.2 and 85.9%, respectively. For mNGS, 6/35 (17%) articles were retained: 459 hematology patients (335 with FN), sensitivity (40-100%) and specificity (40-84%) reported in 3 studies. No articles were found on specific PCR in hematology patients. Improved microbiological documentation was reported in 5, 1, and 5 studies on multiplex-PCR, T2MR, and mNGS, respectively. Faster time to diagnosis was reported in 1, 5, and 1 studies on MALDI-TOF-MS, multiplex-PCR, and T2MR, respectively. Treatment choice was affected by the results of MALDI-TOF-MS, multiplex-PCR, mNGS in 1, 6, and 2 studies, respectively. No significant impact on overall survival or length of stay was reported for any of the tests reviewed.

Conclusions

Limited evidence exists on the performance of non-culture-based diagnostics in hematology patients. Blood cultures should be routinely used, even if new tests are available, which should be used in conjunction with the routine microbiological techniques, until more quality data are available.

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Keywords : Febrile neutropenia, diagnostics, hematologic malignancy, multiplex PCR, next generation sequencing