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Biomarker candidates for the detection of an infectious etiology of febrile neutropenia

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Abstract

Purpose

Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN).

Methods

Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia.

Results

Three peptides (mass to charge ratio 1017.4–1057.3; p-values 0.011–0.024), six proteins (mass to charge ratio 6881–17,215; p-values 0.002–0.004), and six phosphatidylcholines (p-values 0.007–0.037) were identified that differed in FNPI patients compared to patients with infection or bacteremia. Seven of these marker candidates discriminated FNPI from infection at fever onset with higher sensitivity and specificity (ROC-AUC 0.688–0.824) than conventional biomarkers i.e., procalcitonin, C–reactive protein, or interleukin–6 (ROC-AUC 0.535–0.672). In a post hoc analysis, monitoring the time course of four lysophosphatidylcholines, threonine, and tryptophan allowed for discrimination of patients with or without resolution of FN (ROC-AUC 0.648–0.919) with higher accuracy compared to conventional markers (ROC-AUC 0.514–0.871).

Conclusions

Twenty-one promising biomarker candidates for the early detection of an infectious origin or for monitoring the course of FN were found which might overcome known shortcomings of conventional markers.

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Acknowledgments

We wish to thank Viola Bahr, Cora Richert, Julia Köhler, Kay Stötzer, Sandra Wacker, Andrea Naumann, Heike Simon, and Sandra Pöschmann for technical assistance. This study was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1002. The project was further supported by the Paul-Martini-Sepsis Research Group, funded by the Thuringian Ministry of Education, Science and Culture (ProExcellence; grant PE 108-2); the public funded Thuringian Foundation for Technology, Innovation and Research (STIFT), and the German Sepsis Society (GSS).

Author information

Author notes

  1. Herbert G. Sayer

    Present address: 4. Medizinische Klinik (Hämatologie und internistische Onkologie, Hämostaseologie), HELIOS Klinikum Erfurt, Nordhäuser Straße 74, 99089, Erfurt, Germany

Authors and Affiliations

  1. Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany

    Martin E. Richter, Sophie Neugebauer, Falco Engelmann & Michael Kiehntopf

  2. Integriertes Forschungs- und Behandlungszentrum Sepsis und Sepsisfolgen (CSCC), Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany

    Martin E. Richter, Sophie Neugebauer, Stefan Hagel, Katrin Ludewig, Paul La Rosée, Herbert G. Sayer, Andreas Hochhaus, Marie von Lilienfeld-Toal, Christine Pausch & Michael Kiehntopf

  3. Zentrum für Infektionsmedizin und Krankenhaushygiene, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany

    Stefan Hagel

  4. Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie, Infektiologie), Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany

    Stefan Hagel

  5. Klinik für Innere Medizin II, Abt. Hämatologie und Intern. Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany

    Paul La Rosée, Herbert G. Sayer, Andreas Hochhaus & Marie von Lilienfeld-Toal

  6. Leibniz Institut für Naturstoff-Forschung und Infektionsbiologie, Hans-Knöll-Institut, Adolf-Reichwein-Straße 23, 07745, Jena, Germany

    Tom Bretschneider

  7. Institut für Medizinische Informatik, Statistik und Epidemiologie, Universität Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany

    Christine Pausch & Christoph Engel

  8. Zentrum für Klinische Studien, Universitätsklinikum Jena, Salvador-Allende-Platz 27, 07747, Jena, Germany

    Frank M. Brunkhorst

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  1. Martin E. Richter
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  2. Sophie Neugebauer
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Correspondence to Michael Kiehntopf.

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M. E. Richter and S. Neugebauer contributed equally to this manuscript.

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Richter, M.E., Neugebauer, S., Engelmann, F. et al. Biomarker candidates for the detection of an infectious etiology of febrile neutropenia. Infection 44, 175–186 (2016). https://doi.org/10.1007/s15010-015-0830-6

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