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

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

April 2022, pp 1 - 7 Original Article Read Full Article

First Online: 29 April 2022

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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