Metagenomic Sequencing for the Identification of Pathogens in Febrile Neutropenic Patients

The development of targeted therapies and intensive protocols in oncohaematology has improved the survival of patients with haematological malignancies. The increase in the number of patients treated and their life expectancy has been accompanied by an increase in the incidence of infectious complications secondary to the immunosuppression induced by these therapies. Febrile neutropenia (NF) is a complication that occurs in approximately 10% to 15% of patients treated for solid tumours and up to 100% of patients treated for haematological malignancies, particularly after bone marrow and/or haematopoietic stem cell transplantation. In 25% to 30% of cases, NF leads to serious complications. The vast majority of NF cases are caused by microbial infections (bacteria, viruses, fungi, parasites, etc.), which can progress to severe sepsis or septic shock if appropriate treatment is not initiated rapidly (introduction of anti-infective molecules and implementation of associated procedures). If no pathogen is identified during the management of the most severe patients, the prognosis is poor, with a mortality rate of 10%. The performance of diagnostic strategies is therefore an important factor in improving the prognosis of these patients. To date, the reference diagnosis of microorganisms is based on blood cultures, blood Polymerase Chain Reaction (PCR), β-D-glucan and aspergillosis serology. Identifying the pathogens responsible for NF from a blood sample without an a priori hypothesis and in an optimised timeframe could allow earlier treatment of high-risk NF with implications for management (possible modification of antimicrobial and/or immunosuppressive treatment). The aim of this study is to evaluate the performance of the mNGS-DISQVER® tool in diagnosing pathogenic microorganisms from blood samples collected from patients being managed for high-risk NF.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Patient
* Age ≥18 years
* Being treated for solid tumour or haematological malignancy
* Presenting with high-risk febrile neutropenia (high-risk is defined by a Multinational Association for Supportive Care in Cancer (MASCC) score ≥ 21) with an expected duration of neutropenia ≥ 7 days. Neutropenia is defined as an absolute neutrophil count ≤ 500/mm3. Fever is defined as temperature ≥ 38.3°C or ≥ 38°C twice within 1 hour.
* Free, without guardianship, tutelage or subordination;
* covered by a social security scheme or by a third party;
* have given informed consent to participate in the study.

Exclusion Criteria:

* Antibiotic therapy in the 24 hours prior to enrolment, with the exception of prophylactic use of trimethoprim-sulfamethoxazole (Cotrimoxazole) and penicillin G (Oracillin®).
* Previous study participation
* Patients with enhanced protection, i.e. minors, persons deprived of their liberty by a judicial or administrative decision, persons in a health or social care institution, adults under legal protection;
* Pregnant or lactating women of childbearing age (menopause must be documented) who refuse or do not have an effective method of contraception (hormonal/mechanical: per os, injectable, transcutaneous, implantable, intrauterine device or surgical: tubal ligation, hysterectomy, total oophorectomy) for the duration of the study.

• DERIVEDPichon M, Burucoa C; ADNEMIA Study Group. Diagnostic performance of the DISQVER metagenomic sequencing tool for the identification of pathogens in febrile neutropenic patients: the ADNEMIA trial. BMJ Open. 2025 Jan 22;15(1):e087773. doi: 10.1136/bmjopen-2024-087773. PMID 39843376