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Identification of vancomycin interaction with Enterococcus faecalis within 30 min of interaction time using Raman spectroscopy

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Abstract

Vancomycin is an important glycopeptide antibiotic which is used to treat serious infections caused by Gram-positive bacteria. However, during the last years, a tremendous rise in vancomycin resistances, especially among Enterococci, was reported, making fast diagnostic methods inevitable. In this contribution, we apply Raman spectroscopy to systematically characterize vancomycin-enterococci interactions over a time span of 90 min using a sensitive Enterococcus faecalis strain and two different vancomycin concentrations above the minimal inhibitory concentration (MIC). Successful action of the drug on the pathogen could be observed already after 30 min of interaction time. Characteristic spectral changes are visualized with the help of multivariate statistical analysis (linear discriminant analysis and partial least squares regressions). Those changes were employed to train a statistical model to predict vancomycin treatment based on the Raman spectra. The robustness of the model was tested using data recorded by an independent operator. Classification accuracies of >90 % were obtained for vancomycin concentrations in the lower range of a typical trough serum concentration recommended for most patients during appropriate vancomycin therapy. Characterization of drug–pathogen interactions by means of label-free spectroscopic methods, such as Raman spectroscopy, can provide the knowledge base for innovative and fast susceptibility tests which could speed up microbiological analysis as well as finding applications in novel antibiotic screenings assays.

E. faecalis is incubated with vancomycin and characterized by means of Raman spectroscopy after different time points. Characteristic spectral changes reveal efficient vancomycin-enterococci-interaction

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Acknowledgments

Financial support of the BMBF via the Integrated Research and Treatment Center “Center for Sepsis Control and Care” (FKZ 01EO1002) and via the Carl Zeiss Stiftung is highly acknowledged. We thank A. Saupe for the VITEK® measurements as well as Martin Gnauck and Steffen Wolf for recording the scanning electron microscope (SEM) image (graphical abstract).

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The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany

      Cora Assmann, Johanna Kirchhoff, Sophia Kostudis, Peter Schlattmann, Jürgen Popp & Ute Neugebauer

    2. Leibniz Institute of Photonic Technology Jena, Albert-Einstein-Straße 9, 07745, Jena, Germany

      Cora Assmann, Johanna Kirchhoff, Claudia Beleites, Jürgen Popp & Ute Neugebauer

    3. Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, 07743, Jena, Germany

      Jessica Hey & Peter Schlattmann

    4. Institute of Medical Microbiology, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany

      Wolfgang Pfister

    5. Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743, Jena, Germany

      Jürgen Popp

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    1. Cora Assmann
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    Correspondence to Ute Neugebauer.

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    Published in the topical collection Raman4Clinics with guest editors Jürgen Popp and Christoph Krafft.

    Cora Assmann and Johanna Kirchhoff contributed equally to this work.

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    Assmann, C., Kirchhoff, J., Beleites, C. et al. Identification of vancomycin interaction with Enterococcus faecalis within 30 min of interaction time using Raman spectroscopy. Anal Bioanal Chem 407, 8343–8352 (2015). https://doi.org/10.1007/s00216-015-8912-y

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