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Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis

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Abstract

Aims

Flucloxacillin is a frequently used antibiotic in the treatment of spondylodiscitis. We assessed steady-state concentrations and time above minimal inhibitory concentration (fT > MIC) of flucloxacillin in the intervertebral disc, vertebral cancellous bone, subcutaneous tissue and plasma, after intravenous and oral administration.

Methods

Sixteen pigs were randomized into two groups; Group Peroral (Group PO) and Group Intravenous (Group IV) received 1 g flucloxacillin every 6 h for 24 h orally or intravenously. Microdialysis was used for sampling in the compartments of interest. A flucloxacillin target of 50% fT > MIC was applied for three MIC targets: 0.125, 0.5 and 2.0 μg/mL.

Results

Intravenous administration resulted in significantly longer fT > MIC for all targets. Target attainment was only reached for the low target of 0.125 μg/mL in Group IV in vertebral cancellous bone, subcutaneous tissue, and plasma (intervertebral disc 47%). In Group IV, mean fT > MIC values in the investigated compartments were in the range of 47–67% of the dosing interval for 0.125 μg/mL, 20–35% for 0.5 μg/mL, and 0–15% for 2.0 μg/mL. In Group PO, mean fT > MIC values for 0.125 μg/mL were in the range of 1–33%. No pigs reached a concentration of 0.5 μg/mL in any of the investigated compartments in Group PO.

Conclusion

Administration of 1 g flucloxacillin every 6 h resulted in surprisingly low steady-state fT > MIC after intravenous and oral administration. However, intravenous administration resulted in significantly higher concentrations across compartments compared to oral administration. Sufficient target tissue concentrations for treatment of spondylodiscitis may require a dose increase or alternative dosing regimens.

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Funding

The authors wish to thank Sofus Carl Emil Friis Foundation, Aase & Ejnar Danielsen’s Foundation, the Augustinus Foundation, Direktør Emil Hertz og hustru Inger Hertz Foundation, and the Novo Nordisk Foundation for supporting this study financially. No competing interests were declared.

Author information

Authors and Affiliations

  1. Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Mathias A. F. Bendtsen, Pelle Hanberg, Josefine Slater, Jakob Hansen, Kristina Öbrink-Hansen, Maiken Stilling & Mats Bue

  2. Aarhus Microdialysis Research Group, Aarhus University Hospital, Aarhus, Denmark

    Mathias A. F. Bendtsen, Pelle Hanberg, Josefine Slater, Maiken Stilling & Mats Bue

  3. Department of Orthopedic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus, Denmark

    Mathias A. F. Bendtsen, Josefine Slater, Maiken Stilling & Mats Bue

  4. Department of Orthopedic Surgery, Horsens Regional Hospital, Horsens, Denmark

    Pelle Hanberg

  5. Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark

    Kristina Öbrink-Hansen

  6. Institute of Forensic Medicine, Aarhus University, Aarhus, Denmark

    Jakob Hansen

Authors
  1. Mathias A. F. Bendtsen
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  2. Pelle Hanberg
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  6. Maiken Stilling
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  7. Mats Bue
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Contributions

MAFB: Drafted the manuscript. Acquisition, analysis and interpretation of data. PH: Designed the study. Interpretation of data. Critical revision. JS: Acquisition of data. Critical revision. JH: Responsible for chemical analysis of drug levels. Critical revision. KÖ-H: Designed the study. Interpretation of data. Critical revision. MS: Designed the study. Interpretation of data. Critical revision. Supervision of research. Approval of final version to publish. MB: Designed the study. Interpretation of data. Critical revision. Supervision of research. Approval of final version to publish.

Corresponding author

Correspondence to Mathias A. F. Bendtsen.

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All authors have no conflicts of interest to declare with relevance to the present article. All authors have no financial or non-financial interest to disclose in relation to the content of this article. All authors have no affiliation with or involvement in any organisation with financial or non-financial interest in the subject or materials discussed in the present article. All authors declare no financial or proprietary interest in any material discussed in this manuscript

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Bendtsen, M.A.F., Hanberg, P., Slater, J. et al. Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis. Eur Spine J 31, 1508–1514 (2022). https://doi.org/10.1007/s00586-022-07208-9

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  • DOI: https://doi.org/10.1007/s00586-022-07208-9

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