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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

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.

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Authors and Affiliations

Authors

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

Keywords

  • Flucloxacillin
  • Bone
  • Infection
  • Spondylodiscitis
  • Animal model