Cefuroxime concentrations in the anterior and posterior column of the lumbar spine - an experimental porcine study.

Animal study Anterior column Antibiotic prophylaxis Cefuroxime Lumbar spine surgery Microdialysis Pharmacokinetics Posterior column Vertebral column

Journal

The spine journal : official journal of the North American Spine Society
ISSN: 1878-1632
Titre abrégé: Spine J
Pays: United States
ID NLM: 101130732

Informations de publication

Date de publication:
09 2022
Historique:
received: 23 11 2021
revised: 04 03 2022
accepted: 26 05 2022
pubmed: 8 6 2022
medline: 24 8 2022
entrez: 7 6 2022
Statut: ppublish

Résumé

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 pharmacokinetic study of cefuroxime concentrations in an acute preclinical porcine model. 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. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. The primary endpoint was the time above the cefuroxime clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL. The secondary endpoint was tissue penetration (AUC 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 minimal inhibitory concentration for S. aureus of 4 µg/mL after 123 minutes (plasma), 97 minutes (anterior column) and 93 minutes (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. 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 vertebra of the lumbar spine for up to 1.5 hours.

Sections du résumé

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
In vivo experimental pharmacokinetic study of cefuroxime concentrations in an 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. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. The primary endpoint was the time above the cefuroxime clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL. The secondary endpoint was tissue penetration (AUC
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 minimal inhibitory concentration for S. aureus of 4 µg/mL after 123 minutes (plasma), 97 minutes (anterior column) and 93 minutes (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.
CLINICAL SIGNIFICANCE
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 vertebra of the lumbar spine for up to 1.5 hours.

Identifiants

pubmed: 35671945
pii: S1529-9430(22)00233-9
doi: 10.1016/j.spinee.2022.05.010
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
Cefuroxime O1R9FJ93ED

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1434-1441

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declarations of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Magnus A Hvistendahl (MA)

Department of Clinical Medicine, Aarhus University, Aarhus N, Central Denmark Region, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark. Electronic address: maghvi@clin.au.dk.

Mats Bue (M)

Department of Clinical Medicine, Aarhus University, Aarhus N, Central Denmark Region, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark; Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark.

Pelle Hanberg (P)

Department of Clinical Medicine, Aarhus University, Aarhus N, Central Denmark Region, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark.

Alexander Emil Kaspersen (AE)

Department of Clinical Medicine, Aarhus University, Aarhus N, Central Denmark Region, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark.

Anne Vibeke Schmedes (AV)

Department of Clinical Biochemistry and Immunology, Hospital Lillebaelt, Vejle, Southern Denmark Region, Denmark.

Maiken Stilling (M)

Department of Clinical Medicine, Aarhus University, Aarhus N, Central Denmark Region, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark; Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark.

Kristian Høy (K)

Department of Clinical Medicine, Aarhus University, Aarhus N, Central Denmark Region, Denmark; Aarhus Denmark Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark; Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus N, Central Denmark Region, Denmark.

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Classifications MeSH