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Infection. 2016 Apr;44(2):175-86. doi: 10.1007/s15010-015-0830-6. Epub 2015 Aug 15.

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

Author information

1
Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
2
Integriertes Forschungs- und Behandlungszentrum Sepsis und Sepsisfolgen (CSCC), Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
3
Zentrum für Infektionsmedizin und Krankenhaushygiene, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
4
Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie, Infektiologie), Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
5
Klinik für Innere Medizin II, Abt. Hämatologie und Intern. Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
6
4. Medizinische Klinik (Hämatologie und internistische Onkologie, Hämostaseologie), HELIOS Klinikum Erfurt, Nordhäuser Straße 74, 99089, Erfurt, Germany.
7
Leibniz Institut für Naturstoff-Forschung und Infektionsbiologie, Hans-Knöll-Institut, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.
8
Institut für Medizinische Informatik, Statistik und Epidemiologie, Universität Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
9
Zentrum für Klinische Studien, Universitätsklinikum Jena, Salvador-Allende-Platz 27, 07747, Jena, Germany.
10
Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany. michael.kiehntopf@med.uni-jena.de.
11
Integriertes Forschungs- und Behandlungszentrum Sepsis und Sepsisfolgen (CSCC), Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany. michael.kiehntopf@med.uni-jena.de.

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.

KEYWORDS:

Biomarkers; Febrile neutropenia; Infection; Metabolome; Proteome

PMID:
26275448
DOI:
10.1007/s15010-015-0830-6
[Indexed for MEDLINE]

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