STEADY-STATE PENICILLIN G DISTRIBUTION IN CERVICAL PARAVERTEBRAL MUSCLE, VERTEBRAL BONE, AND INTERVERTEBRAL DISC: INSIGHTS FROM A PORCINE MICRODIALYSIS STUDY

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Aim Spondylodiscitis requires prolonged antimicrobial therapy and carries a high relapse risk. There is a paucity of targeted tissue pharmacokinetic data on the β-lactam antibiotic penicillin G, which is commonly used in the management of spondylodiscitis caused by susceptible strains of Staphylococcus aureus (S. aureus) and Streptococcus (Strep.) species. This study aimed to assess the time for which steady-state concentrations of penicillin G exceeded targeted minimum inhibitory concentrations (T>MIC) in cervical spine tissues. Method 6 female pigs received intravenous penicillin G (1.2 g bolus every 6 h) over 18 h, in accordance with spondylodiscitis treatment guidelines. Microdialysis sampling was performed in cervical paravertebral muscle, vertebral cancellous bone (C3), and intervertebral disc (C3/C4). Samples were collected during the third dosing interval (12-18 h; simulating a steady-state therapeutic setting). Plasma samples were collected for reference. MIC targets of 0.125 mg/L ( S. aureus breakpoint), 0.25 mg/L ( Strep. Groups A, B, C, and G breakpoint) and 0.5 mg/L (4 x MIC for S. aureus ) were applied and evaluated at 50% and 100% T>MIC. Results Across the investigated MIC targets (0.125, 0.25, and 0.5 mg/L), T>MIC ranged from 81-99% for paravertebral muscle, 72-91% for vertebral bone, and 77-86% for intervertebral disc. In the paravertebral muscle, 6/6 pigs met the target of 50% T>MIC at MIC 0.125 and 0.25 mg/L, whereas 4/6 achieved it at 0.5 mg/L. In vertebral bone 6/6, 5/6, and 4/6 pigs met the 50% T>MIC target at 0.125, 0.25, and 0.5 mg/L, respectively, while in intervertebral disc, 5/6 pigs met the target at all MIC levels. For the 100% T>MIC target at MIC 0.5 mg/L, 2/6 pigs attained the target in paravertebral muscle, compared to 1/6 in both vertebral bone and intervertebral disc. Conclusions Adherence to current penicillin G dosing guidelines resulted in 50% T>MIC for low-MIC strains (0.125 and 0.25 mg/L) in cervical spine soft tissue and bone. To achieve complete tissue exposure (100% T>MIC) against high-MIC strains (≥ 0.5 mg/L), intensified or alternative penicillin G regimens may be required to improve spondylodiscitis treatment. Acknowledgements The Kirsten and Freddy Johansen Foundation, Novo Nordisk Foundation, Beckett Foundation, Hede Nielsen Family Foundation, King Christian X Foundation, A.P. Møller Foundation, Dagmar Marshalls Foundation, and Carl and Ellen Hertz Foundation.

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