Purpose Spondylodiscitis is a serious condition requiring prolonged antibiotic therapy. Relevant pharmacokinetic tissue understanding of antibiotics in a spondylodiscitis setting is limited. The study aimed to investigate cefuroxime concentrations in the L4/L5 intervertebral disc, lumbar bone, paravertebral muscle and subcutaneous tissue using microdialysis. Methods Eight pigs received 1,500 mg of cefuroxime by intravenous bolus infusion over 10 min. Prior to cefuroxime administration, microdialysis catheters were placed in the L4/L5 intervertebral disc, lumbar bone, paravertebral muscle and adjacent subcutaneous tissue for sampling across an 8-h dosing interval. Plasma samples were obtained for reference. Based on prior time-kill modelling for cefuroxime, 40% of the dosing interval with concentrations above the minimum inhibitory concentration (40% T > MIC) for Staphylococcus aureus was chosen as the primary endpoint. Results The 40% T > MIC target exposure was surpassed in all investigated compartments in 5/8 pigs at the lowest MIC-target of 1 <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="586_2025_8718_Article_IEq1.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="15" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:\mu\:\)</EquationSource> </InlineEquation>g/mL. None of the pigs achieved the 40% T > MIC at the clinical breakpoint MIC for S. aureus of 4 <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="586_2025_8718_Article_IEq1.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="15" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:\mu\:\)</EquationSource> </InlineEquation>g/mL. Mean %T > MIC was comparable across the spondylodiscitis relevant tissues at MICs of 1 (range: 43–60%), 2 (range: 30–38%)<InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="586_2025_8718_Article_IEq3.gif" Format="GIF" Height="7" Rendition="HTML" Resolution="72" Type="Linedraw" Width="8" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:,\)</EquationSource> </InlineEquation> and 4 <InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="586_2025_8718_Article_IEq1.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="15" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:\mu\:\)</EquationSource> </InlineEquation>g/mL (range: 16–26%). Conclusion Short-infused cefuroxime dosing standards may under-treat S. aureus spondylodiscitis, increasing the risk of inadequate bacterial killing and resistance development. Given the severity of spondylodiscitis, alternate clinical dosing strategies for cefuroxime may be necessary, such as shorter dosing intervals or prolonged/continuous infusion.

Spondylodiscitis relevant tissue concentrations of cefuroxime - a large animal microdialysis study

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2025年2月14日

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Jake Paul Lawrence Bastian,
Magnus A. Hvistendahl,
Kristian Høy,
Maiken Stilling,
Mats Bue

摘要

Purpose

Spondylodiscitis is a serious condition requiring prolonged antibiotic therapy. Relevant pharmacokinetic tissue understanding of antibiotics in a spondylodiscitis setting is limited. The study aimed to investigate cefuroxime concentrations in the L4/L5 intervertebral disc, lumbar bone, paravertebral muscle and subcutaneous tissue using microdialysis.

Methods

Eight pigs received 1,500 mg of cefuroxime by intravenous bolus infusion over 10 min. Prior to cefuroxime administration, microdialysis catheters were placed in the L4/L5 intervertebral disc, lumbar bone, paravertebral muscle and adjacent subcutaneous tissue for sampling across an 8-h dosing interval. Plasma samples were obtained for reference. Based on prior time-kill modelling for cefuroxime, 40% of the dosing interval with concentrations above the minimum inhibitory concentration (40% T > MIC) for Staphylococcus aureus was chosen as the primary endpoint.

Results

The 40% T > MIC target exposure was surpassed in all investigated compartments in 5/8 pigs at the lowest MIC-target of 1 \(\:\mu\:\) g/mL. None of the pigs achieved the 40% T > MIC at the clinical breakpoint MIC for S. aureus of 4 \(\:\mu\:\) g/mL. Mean %T > MIC was comparable across the spondylodiscitis relevant tissues at MICs of 1 (range: 43–60%), 2 (range: 30–38%) \(\:,\) and 4 \(\:\mu\:\) g/mL (range: 16–26%).

Conclusion

Short-infused cefuroxime dosing standards may under-treat S. aureus spondylodiscitis, increasing the risk of inadequate bacterial killing and resistance development. Given the severity of spondylodiscitis, alternate clinical dosing strategies for cefuroxime may be necessary, such as shorter dosing intervals or prolonged/continuous infusion.