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In-hospital metabolite changes in infective endocarditis—a longitudinal 1H NMR-based study

  • Christine Falk KleinEmail author
  • Sarah Louise Kjølhede Holle
  • Malene Højgaard Andersen
  • Anders Pedersen
  • Henning Bundgaard
  • Kasper Karmark Iversen
  • Anders MalmendalEmail author
Original Article

Abstract

Treatment of infective endocarditis (IE) is a 4–6-week provided course of intravenously administered antibiotics. The aim of this study was to investigate how serum metabolites as measured by proton nuclear magnetic resonance (1H NMR) spectroscopy are changing over time during the active phase of IE, and to see whether these metabolite changes might be used to monitor recovery in these patients. Patients hospitalized with first-time IE at Herlev Hospital, Denmark, from September 2015 to June 2017 were included. Longitudinal blood sampling was performed and serum was analyzed using 1H NMR. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was used to separate sample groups and analyze differences in metabolite profiles. Thirteen patients were included in the study (77% men, median age 62 years (IQR 53–77)). All patients were cured during the hospitalization without any relapse during 6 months of follow-up. We analyzed 61 serum samples (median 5 samples, range 2–8 per person) drawn in the treatment period after IE diagnosis. The main changes during the in-hospital period were decreased levels of glucose, mannose, leucine, isoleucine, phenylalanine, tyrosine, and signals from polyols and N-acetylated protein. The metabolomic changes could in contrast to the routinely used parameters CRP and leucocyte levels distinguish between the early and late stages of disease treatment. We present the first longitudinal study of 1H NMR metabolomics in patients with infective endocarditis. The metabolomic changes show a promising strength compared to routinely used clinical parameters.

Keywords

Infective endocarditis Antibiotic treatment Metabolomics NMR Longitudinal study 

Notes

Acknowledgments

The authors gratefully acknowledge support from Dr. Christian Pihl and the medical student Mia Pries-Heje for helping with the sample collection process.

Author contributions

HB, KI, AM, and CFK conceived and designed the study. CFK, SLKH, and MHA included the patients, and collected and prepared the blood samples. CFK, AM, and AP made the NMR spectral analyses. AM made the statistical analyses. CFK drafted the manuscript, and SLKH, MHA, AP, HB, KI, and AM revised the manuscript critically for intellectual content, and have read and approved the final manuscript for submission.

Funding

This work was supported by the Herlev Hospital Research Council and FUKAP (research fund of The Department of Cardiology, Copenhagen University Hospital Gentofte). The funder did not have any role in designing or conducting the study, neither data collection, data analyses, nor manuscript approval.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Danish Data Protection Agency (j.nr.: 2012-58-0004, local j.nr.: HGH-2015-010, I-suite number: 03923) and the Danish Scientific Ethics Committee (protocol number: H-15009681).

Informed consent

All patients included in this study participated after having given informed consent.

Supplementary material

10096_2019_3586_MOESM1_ESM.docx (2.7 mb)
ESM 1 (DOCX 2772 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyHerlev Gentofte HospitalCopenhagenDenmark
  2. 2.The Swedish NMR CentreUniversity of GothenburgGöteborgSweden
  3. 3.Department of CardiologyCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  4. 4.Copenhagen Health Science PartnersKøbenhavnDenmark
  5. 5.Department of ChemistryLund UniversityLundSweden

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