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

doi:10.1007/s00586-022-07208-9

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

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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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.

Original language	English
Journal	European Spine Journal
Volume	31
Issue	6
Pages (from-to)	1508-1514
Number of pages	7
ISSN	0940-6719
DOIs	https://doi.org/10.1007/s00586-022-07208-9
Publication status	Published - Jun 2022

Keywords

Animal model
Bone
Flucloxacillin
Infection
Spondylodiscitis

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10.1007/s00586-022-07208-9

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Bendtsen, M. A. F., Hanberg, P., Slater, J., Hansen, J., Öbrink-Hansen, K., Stilling, M., & Bue, M. (2022). Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis. European Spine Journal, 31(6), 1508-1514. https://doi.org/10.1007/s00586-022-07208-9

@article{5d5e47087c884043b8f797e2bc120ee7,

title = "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.",

keywords = "Animal model, Bone, Flucloxacillin, Infection, Spondylodiscitis",

author = "Bendtsen, {Mathias A.F.} and Pelle Hanberg and Josefine Slater and Jakob Hansen and Kristina {\"O}brink-Hansen and Maiken Stilling and Mats Bue",

note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2022",

month = jun,

doi = "10.1007/s00586-022-07208-9",

language = "English",

volume = "31",

pages = "1508--1514",

journal = "European Spine Journal",

issn = "0940-6719",

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Bendtsen, MAF , Hanberg, P , Slater, J , Hansen, J, Öbrink-Hansen, K, Stilling, M & Bue, M 2022, 'Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis', European Spine Journal, vol. 31, no. 6, pp. 1508-1514. https://doi.org/10.1007/s00586-022-07208-9

Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis. / Bendtsen, Mathias A.F.; Hanberg, Pelle ; Slater, Josefine et al.
In: European Spine Journal, Vol. 31, No. 6, 06.2022, p. 1508-1514.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis

AU - Bendtsen, Mathias A.F.

AU - Hanberg, Pelle

AU - Slater, Josefine

AU - Hansen, Jakob

AU - Öbrink-Hansen, Kristina

AU - Stilling, Maiken

AU - Bue, Mats

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - Animal model

KW - Bone

KW - Flucloxacillin

KW - Infection

KW - Spondylodiscitis

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U2 - 10.1007/s00586-022-07208-9

DO - 10.1007/s00586-022-07208-9

M3 - Journal article

C2 - 35488132

AN - SCOPUS:85129140482

SN - 0940-6719

VL - 31

SP - 1508

EP - 1514

JO - European Spine Journal

JF - European Spine Journal

IS - 6

ER -

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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