BACKGROUND CONTEXT Surgical site infection following spine surgery is associated with increased morbidity and mortality. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and many surgeries involve the lumbar spine. PURPOSE The objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column during lumbar spine surgery with a posterior surgical approach. STUDY DESIGN/SETTING In vivo experimental pharmacokinetics study of cefuroxime concentrations in an acute preclinical porcine model. OUTCOME MEASURES The primary end-point was the time above cefuroxime clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL. The secondary end-point was tissue penetration (AUCtissue/AUCplasma). METHODS The lumbar vertebral column was exposed from L1 to L5 in eight female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously. Microdialysates and plasma samples were continously obtained over eight hours. Cefuroxime concentration were quantified by ultra high-performance liquid chromatography tandem mass spectrometry. RESULTS Mean T>MIC 4 µg/mL (95% confidence interval) was 123 min (105-141) in plasma, 97 min (79-115) in the anterior column and 93 min (75-111) in the posterior column. Tissue penetration (95% confidence interval) was incomplete for both the anterior column 0.48 (0.40-0.56) and posterior column 0.40 (0.33-0.48). CONCLUSIONS T>MIC was comparable between the anterior and posterior column. Mean cefuroxime concentrations decreased below the clinical breakpoint MIC for S. aureus of 4 µg/mL after 123 min (plasma), 97 min (anterior column) and 93 min (posterior column). Open lumbar spine surgery often involves extensive soft tissue dissection, stripping and retraction of the paraspinal muscles which may impair the local blood flow exposing the lumbar vertebra to postoperative infections. A single intravenous administration of 1.5 g cefuroxime only provided sufficient prophylactic target tissue concentrations in the vertebrae of the lumber spine for up to 1.5 hours. This is shorter than the duration of most lumbar spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 1.5 hours. FDA DEVICE/DRUG STATUS cefuroxime (Approved for this indication). Surgical site infection following spine surgery is associated with increased morbidity and mortality. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and many surgeries involve the lumbar spine. The objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column during lumbar spine surgery with a posterior surgical approach. In vivo experimental pharmacokinetics study of cefuroxime concentrations in an acute preclinical porcine model. The primary end-point was the time above cefuroxime clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL. The secondary end-point was tissue penetration (AUCtissue/AUCplasma). The lumbar vertebral column was exposed from L1 to L5 in eight female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously. Microdialysates and plasma samples were continously obtained over eight hours. Cefuroxime concentration were quantified by ultra high-performance liquid chromatography tandem mass spectrometry. Mean T>MIC 4 µg/mL (95% confidence interval) was 123 min (105-141) in plasma, 97 min (79-115) in the anterior column and 93 min (75-111) in the posterior column. Tissue penetration (95% confidence interval) was incomplete for both the anterior column 0.48 (0.40-0.56) and posterior column 0.40 (0.33-0.48). T>MIC was comparable between the anterior and posterior column. Mean cefuroxime concentrations decreased below the clinical breakpoint MIC for S. aureus of 4 µg/mL after 123 min (plasma), 97 min (anterior column) and 93 min (posterior column). Open lumbar spine surgery often involves extensive soft tissue dissection, stripping and retraction of the paraspinal muscles which may impair the local blood flow exposing the lumbar vertebra to postoperative infections. A single intravenous administration of 1.5 g cefuroxime only provided sufficient prophylactic target tissue concentrations in the vertebrae of the lumber spine for up to 1.5 hours. This is shorter than the duration of most lumbar spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 1.5 hours.