Incomplete cefuroxime penetration to the anterior and posterior column of the lumbar spine – An experimental porcine study — The International Society for the Study of the Lumbar Spine
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Incomplete cefuroxime penetration to the anterior and posterior column of the lumbar spine – An experimental porcine study (#1135)

Magnus A. Hvistendahl 1 2 , Pelle Hanberg 1 2 , Mats Bue 1 2 3 , Alexander Emil Kaspersen 1 2 , Anne V. Schmedes 4 , Maiken Stilling 1 2 3 , Kristian Høy 5
  1. Department of Clinical Medicine, Aarhus University, Aarhus, Central Jutland, Denmark
  2. Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Jutland, Denmark
  3. Department Of Orthopedic Surgery, Aarhus University Hospital, Aarhus N, Central Jutland, Denmark
  4. Department of Clinical Biochemistry and Immunology, Hospital Lillebaelt, Vejle, South Jutland, Denmark
  5. Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus N, Central Jutland, Denmark

Introduction

Surgical site infection following spine surgery is associated with increased morbidity and possibly mortality as well as increased cost for the health care system. The reported pooled incidence is 3%. 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 often involve the lumbar spine. Along with the potential of achieving subtherapeutic perioperative antibiotic concentrations across the vertebral column, particularly in posterior spine surgery due to a theoretically impaired blood flow to the PC, it seems prudent to investigate cefuroxime concentrations across the vertebral column. Accordingly, the objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column of the same lumbar vertebrae using microdialysis in an in vivo experimental acute preclinical porcine model.

 

Methods

The lumbar vertebral column was exposed from L1 to L5 in 8 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 over 10 min. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. Microdialysis is a catheter-based pharmacokinetic tool, that allows dynamic sampling of unbound and pharmacologic active fraction of drugs e.g., cefuroxime. The primary endpoint was the time with cefuroxime above the clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL as this has been suggested as the best predictor of efficacy for cefuroxime. The secondary endpoint was tissue penetration (AUCtissue/AUCplasma).

 

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).

 

Discussion

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 resulted in comparable T>MIC between the anterior and posterior column of the lumbar spine. 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). 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.

 

Figure 1. Cefuroxime concentration-time profiles. Arrow: time of cefuroxime administration.

619c2016d9d7f-Figure+2.+Cefuroxime+concentration-time+profiles.jpg

 

Figure 2. Illustration of the investigated area (a), placement of microdialysis catheters (b) and the microdialysis method (c). Red dots: cefuroxime, blue dots: meropenem as internal calibrator.

619c2016d9d7f-Figure+1.+Illustration+of+placement+of+MD-catheters.jpg

 

 

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