Evaluation of cefuroxime concentration in the intrathecal and extrathecal compartments of the lumbar spine-an experimental study in pigs.

Autor: Kaspersen AE; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark., Hanberg P; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark., Hvistendahl MA; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark., Bue M; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark.; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark., Schmedes AV; Department of Clinical Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark., Høy K; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark., Stilling M; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark.; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2023 Jul; Vol. 180 (14), pp. 1832-1842. Date of Electronic Publication: 2023 Feb 22.
DOI: 10.1111/bph.16045
Abstrakt: Background and Purpose: Optimal antibiotic prophylaxis is crucial to prevent postoperative infection in spinal surgery. Sufficient time above the minimal inhibitory concentration (fT > MIC) for relevant bacteria in target tissues is required for cefuroxime. We assessed cefuroxime concentrations and fT > MIC of 4 μg·ml -1 for Staphylococcus aureus in the intrathecal (spinal cord and cerebrospinal fluid, CSF) and extrathecal (epidural space) compartments of the lumbar spine.
Experimental Approach: Eight female pigs were anaesthetized and laminectomized at L3-L4. Microdialysis catheters were placed for sampling in the spinal cord, CSF, and epidural space. A single dose of 1500 mg cefuroxime was administered intravenously over 10 min. Microdialysates and plasma were obtained continuously during 8 h. Cefuroxime concentrations were determined by ultra-high-performance liquid chromatography.
Key Results: Mean fT > MIC (4 μg·ml -1 ) was 58 min in the spinal cord, 0 min in the CSF, 115 min in the epidural space, and 123 min in plasma. Tissue penetration was 32% in the spinal cord, 7% in the CSF, and 63% in the epidural space.
Conclusion and Implications: fT > MIC (4 μg·ml -1 ) and tissue penetration for cefuroxime were lower in the intrathecal compartments (spinal cord and CSF) than in the extrathecal compartment (epidural space) and plasma, suggesting a significant effect of the blood-brain barrier. In terms of fT > MIC, a single dose of 1500 mg cefuroxime seems inadequate to prevent intrathecal infections related to spinal surgery for bacteria presenting with a MIC target of 4 μg· ml -1 or above.
(© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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