Bastian Jake Paul Lawrence, Hvistendahl Magnus A, Høy Kristian, Stilling Maiken, Bue Mats
Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus N, Denmark.
Eur Spine J. 2025 Feb 14. doi: 10.1007/s00586-025-08718-y.
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.
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.
The 40% T > MIC target exposure was surpassed in all investigated compartments in 5/8 pigs at the lowest MIC-target of 1 [Formula: see text]g/mL. None of the pigs achieved the 40% T > MIC at the clinical breakpoint MIC for S. aureus of 4 [Formula: see text]g/mL. Mean %T > MIC was comparable across the spondylodiscitis relevant tissues at MICs of 1 (range: 43-60%), 2 (range: 30-38%)[Formula: see text] and 4 [Formula: see text]g/mL (range: 16-26%).
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.
脊椎椎间盘炎是一种需要长期抗生素治疗的严重疾病。在脊椎椎间盘炎情况下，对抗生素相关药代动力学组织的了解有限。本研究旨在使用微透析研究头孢呋辛在L4/L5椎间盘、腰椎骨、椎旁肌肉和皮下组织中的浓度。
8头猪在10分钟内通过静脉推注接受1500mg头孢呋辛。在给予头孢呋辛之前，将微透析导管放置在L4/L5椎间盘、腰椎骨、椎旁肌肉和相邻皮下组织中，以在8小时给药间隔内进行采样。采集血浆样本作为参考。根据先前头孢呋辛的时间杀菌模型，选择浓度高于金黄色葡萄球菌最低抑菌浓度（40%T＞MIC）的给药间隔的40%作为主要终点。
在最低MIC目标为1μg/mL时，5/8头猪的所有研究隔室均超过了40%T＞MIC目标暴露。在金黄色葡萄球菌临床断点MIC为4μg/mL时，没有一头猪达到40%T＞MIC。在MIC为1μg/mL（范围：43 - 60%）、2μg/mL（范围：30 - 38%）和4μg/mL（范围：16 - 26%）时，脊椎椎间盘炎相关组织的平均%T＞MIC相当。
短时间输注头孢呋辛的给药标准可能无法充分治疗金黄色葡萄球菌性脊椎椎间盘炎，增加细菌杀灭不足和耐药性发展的风险。鉴于脊椎椎间盘炎的严重性，可能需要替代的头孢呋辛临床给药策略，如更短的给药间隔或延长/持续输注。
