Vancomycin concentrations in the cervical spine after intravenous administration: results from an experimental pig study

Abstract

Background and purpose - Vancomycin may be an important drug for intravenous perioperative antimicrobial prophylaxis in spine surgery. We assessed single-dose vancomycin intervertebral disc, vertebral cancellous bone, and subcutaneous adipose tissue concentrations using microdialysis in a pig model. Material and methods - 8 female pigs received 1,000 mg of vancomycin intravenously as a single dose over 100 minutes. Microdialysis probes were placed in the C3-C4 intervertebral disc, C3 vertebral cancellous bone, and subcutaneous adipose tissue, and vancomycin concentrations were obtained over 8 hours. Venous blood samples were obtained as reference. Results - Ranging from 0.24 to 0.60, vancomycin tissue penetration, expressed as the ratio of tissue to plasma area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments. The lowest penetration was found in the intervertebral disc. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 4 µg/mL was 3, 17, 25, and 156 min for plasma, subcutaneous adipose tissue, vertebral cancellous bone, and the intervertebral disc, respectively. In contrast to the other compartments, a mean MIC of 8 µg/mL was not reached in the intervertebral disc. An approximately 3-times longer elimination rate was observed in the intervertebral disc in comparison with all the other compartments (p < 0.001), and the time to peak drug concentration was higher for all tissues compared with plasma Interpretation - Preoperative administration of 1,000 mg of vancomycin may provide adequate vancomycin tissue concentrations with a considerable delay, though tissue penetration was incomplete. However, in order also to achieve adequate intervertebral disc concentrations in all individuals and accommodating a potentially higher MIC target, supplemental application of vancomycin may be necessary.

Microdialysis for the Assessment of Intervertebral Disc and Vertebral Cancellous Bone Metabolism in a Large Porcine Model

“…With reference to reduction, refinement and replacement (the 3Rs), the present study was based on microdialysis dialysates previously obtained and included in a pharmacokinetic study investigating the penetration of vancomycin into the C3-C4 intervertebral disc, the C3 vertebral cancellous bone, and subcutaneous adipose tissue (15). As such, the present study fulfils the expectation of reduction, as the material is collected from previously used pigs, instead of using new pigs to generate similar results.…”

“…The catheter was fixed to the splittable introducer with endo clips. Fluoroscopy was applied for the evaluation of correct placement of the catheters in the C3 vertebral body and the C3-C4 intervertebral disc (15). As references, a subcutaneous adipose tissue catheter (membrane length 20 mm) was inserted in the lateral part of the right thigh, and a central venous catheter was placed for subsequent venous blood sampling.…”

“…The penetration of vancomycin was found to be significantly incomplete and delayed to the intervertebral disc and vertebral cancellous bone. A more thorough discussion of the resulting pharmacokinetic data can be found elsewhere (15).…”

“…For the particular cases of bone tissue and the intervertebral disc, microdialysis has only been applied for the assessment of metabolism in the femoral head of humans and pigs, and in a cadaver study, respectively (11)(12)(13)(14). To date, microdialysis sampling from vertebral cancellous bone and the intervertebral disc has been limited to antimicrobials in a porcine model (15,16). As it may be challenging to identify a clinical model to assess in vivo spine tissue biochemistry without causing any harm to the patients, a large porcine model may prove to be important for further understanding of the metabolism and pathogenesis in spine tissue.…”

“…This study was based on microdialysis dialysates obtained from 7 experimental pigs (Danish Landrace Breed; weight 78-82 kg). The pigs were included in a pharmacokinetic study investigating the penetration of vancomycin into the C3-C4 intervertebral disc, the C3 vertebral cancellous bone, and subcutaneous adipose tissue (15).…”