DOS 2018

200 · DOS Abstracts Single-Dose Pharmacokinetics of Meropenem in Porcine Cancellous Bone Determined by Microdialysis Pelle Hanberg, Andrea Lund, Kjeld Søballe, Mats Bue Department of Orthopaedic Surgery, Horsens Regional Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital Background: Bone infections are difficult to treat, which may partly be ex- plained by an incomplete and heterogeneous tissue distribution of antimicrobi- als. In the specific cases of open tibial fractures and chronic osteomyelitis, litera- ture have been inconclusive regarding choice of antimicrobial treatment. Recent studies suggest the use of meropenem for patients with open tibial fractures or chronic osteomyelitis. Purpose / Aim of Study: The objective of this study was to describe the me- ropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT) and cancellous bone using microdialysis in a porcine model. Materials and Methods: Six female pigs were assigned to receive 1 g of me- ropenem intravenously over 5 min. Measurements of meropenem were ob- tained from plasma, SCT and cancellous bone of the tibial condyle for 8 hours thereafter. Microdialysis was applied for sampling in solid tissues. The merope- nem concentration was determined using UHPLC. Findings / Results: Tissue penetration of meropenem from plasma to cancel- lous bone was incomplete and delayed. Comparing cancellous bone with both plasma and SCT, the elimination rate and maximal concentration of meropenem was prolonged and lower, respectively. The T>MIC, for a MIC of 0.5 μg/mL, was shorter for the cancellous bone compared with both plasma and SCT. For MICs above 0.5 μg/mL T>MIC in cancellous bone was only shorter than SCT. Considering a MIC of 4 μg/mL, reflecting a worst-case scenario, no animals achieved the target of 40% T>MIC in plasma and cancellous bone, while only 17% achieved it in the SCT. Conclusions: The main finding of this study was short T>MIC in cancellous bone after intravenous administration of 1 g meropenem. Consequently, our data suggest that higher doses or other ways of applying meropenem, should be considered in the cases of open tibial fractures and chronic osteomyelitis. 141.