Concentrations of Co-Administered Meropenem and Vancomycin in Spinal Tissues Relevant for the Treatment of Pyogenic Spondylodiscitis-An Experimental Microdialysis Study

Josefine Slater; Maiken Stilling; Pelle Hanberg; Sofus Vittrup; Martin Bruun Knudsen; Sara Kousgaard Tøstesen; Josephine Olsen Kipp; Mats Bue

doi:10.3390/antibiotics12050907

Concentrations of Co-Administered Meropenem and Vancomycin in Spinal Tissues Relevant for the Treatment of Pyogenic Spondylodiscitis-An Experimental Microdialysis Study

Antibiotics (Basel). 2023 May 14;12(5):907. doi: 10.3390/antibiotics12050907.

Authors

Josefine Slater^{1

2

3}, Maiken Stilling^{1

2

3}, Pelle Hanberg^{1

3}, Sofus Vittrup^{1

2

3}, Martin Bruun Knudsen^{1

2

3}, Sara Kousgaard Tøstesen^{1

2

3}, Josephine Olsen Kipp^{1

2

3}, Mats Bue^{1

2

3}

Affiliations

¹ Department of Orthopaedic Surgery, Aarhus University Hospital, 8200 Aarhus, Denmark.
² Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark.
³ Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, 8200 Aarhus, Denmark.

Abstract

Co-administration of meropenem and vancomycin has been suggested as a systemic empirical antibiotic treatment of pyogenic spondylodiscitis. The aim of this study was, in an experimental porcine model, to evaluate the percentage of an 8-h dosing interval of co-administered meropenem and vancomycin concentrations above the relevant minimal inhibitory concentrations (MICs) (%T>MIC) in spinal tissues using microdialysis. Eight female pigs (Danish Landrace breed, weight 78-82 kg) received a single-dose bolus infusion of 1000 mg of meropenem and 1000 mg vancomycin simultaneously before microdialysis sampling. Microdialysis catheters were applied in the third cervical (C3) vertebral cancellous bone, the C3-C4 intervertebral disc, paravertebral muscle, and adjacent subcutaneous tissue. Plasma samples were obtained for reference. The main finding was that for both drugs, the %T>MICs were highly reliant on the applied MIC target, but were heterogeneous across all targeted tissues, ranging from 25-90% for meropenem, and 10-100% for vancomycin. For both MIC targets, the highest %T>MIC was demonstrated in plasma, and the lowest %T>MIC was demonstrated in the vertebral cancellous bone for meropenem, and in the intervertebral disc for vancomycin. When indicated, our findings may suggest a more aggressive dosing approach of both meropenem and vancomycin to increase the spinal tissue concentrations to treat the full spectrum of potentially encountered bacteria in a spondylodiscitis treatment setting.

Keywords: antibiotic stewardship; meropenem; microdialysis; pharmacodynamics; pharmacokinetics; spinal tissues; spondylodiscitis; target site; vancomycin.

Grants and funding

Funding for this research was received from the Orthopaedic Research Unit, Aarhus University Hospital. The funding party was not involved in the present research. No benefits in any form have been received from a commercial party related indirectly or directly to this article.