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Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics.

ABSTRACT: BackgroundNovel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies.MethodsAltogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite profiling analysis by liquid chromatography-mass spectrometry were taken when fever rose over 38° and on the next morning.ResultsAltogether, 90 differential molecular features were shown to explain the differences between patients with complicated (bacteremia, severe sepsis, or fatal outcome) and noncomplicated courses of febrile neutropenia. The most differential compounds were an androgen hormone, citrulline, and phosphatidylethanolamine PE(18:0/20:4). The clinical relevance of the findings was evaluated by comparing them with conventional biomarkers like C-reactive protein and procalcitonin.ConclusionThese results hold promise to find out novel biomarkers for febrile neutropenia, including citrulline. Furthermore, androgen metabolism merits further studies.

SUBMITTER: Lappalainen M

PROVIDER: S-EPMC5925027 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics.

Lappalainen Marika M Jokkala Jenna J Juutilainen Auni A Hämäläinen Sari S Koivula Irma I Jantunen Esa E Hanhineva Kati K Pulkki Kari K

Disease markers 20180412

<h4>Background</h4>Novel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies.<h4>Methods</h4>Altogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite p ...[more]

PMID: 29849825

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Project description:BackgroundThe 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients.MethodsWe conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January-October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death.ResultsOverall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15-0.53, p < 0.001).ConclusionImplementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.

Dataset Information

Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics.

Publications

Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics.

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