Pharmacokinetics of double-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone-a randomized microdialysis study.
Cefuroxime
Intervertebral disc
Microdialysis
Pharmacokinetics
Tissue penetration
Vertebra
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:
08 2020
08 2020
Historique:
received:
03
10
2019
revised:
13
02
2020
accepted:
07
03
2020
pubmed:
21
3
2020
medline:
25
6
2021
entrez:
21
3
2020
Statut:
ppublish
Résumé
Postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Cefuroxime is a time-dependent antimicrobial widely used for intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime (1.5 g) provides insufficient spine tissue concentrations for spine procedures lasting more than 2 to 3 hours. To evaluate the time with concentrations above relevant minimal inhibitory concentrations (T>MIC) in plasma, subcutaneous adipose tissue, vertebral cancellous bone, and intervertebral disc after a twofold increase of the standard dosage of 1.5 g cefuroxime given as one double dose (1×3 g) or two single doses (2×1.5 g) with a four-hour interval. Sixteen pigs were randomized into two groups: Group 1 received one double dose of cefuroxime (1×3 g) as an intravenous bolus and Group 2 received two single doses of cefuroxime (2×1.5 g) as an intravenous bolus with a four-hour interval. Cefuroxime measurements were obtained from plasma, subcutaneous adipose tissue, vertebral cancellous bone, and intervertebral disc for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography. This work was supported by grants from the Health Research Foundation of Central Denmark Region (Level E). The funding source did not play any role in the investigation. The time with concentrations above the Staphylococcus aureus clinical breakpoint minimal inhibitory concentration of 4 μg/mL was higher in all compartments for Group 2 compared to Group 1. The mean T>MIC (4 μg/mL) in all compartments ranged between 47% and 67% for Group 1 and 72% and 92% for Group 2. Furthermore, a delayed tissue penetration into all tissues for both groups was demonstrated. This study suggests that cefuroxime should be given at least 45 minutes prior to spine procedures and as two single doses at a maximum interval of four hours for extended spine procedures. Clinical studies verifying these results are warranted. Administering cefuroxime as two single doses (2×1.5 g) with a four-hour interval compared to one double dose (1×3 g) resulted in higher T>MIC. Furthermore, we found delayed and incomplete cefuroxime tissue penetration.
Sections du résumé
BACKGROUND CONTEXT
Postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Cefuroxime is a time-dependent antimicrobial widely used for intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime (1.5 g) provides insufficient spine tissue concentrations for spine procedures lasting more than 2 to 3 hours.
PURPOSE
To evaluate the time with concentrations above relevant minimal inhibitory concentrations (T>MIC) in plasma, subcutaneous adipose tissue, vertebral cancellous bone, and intervertebral disc after a twofold increase of the standard dosage of 1.5 g cefuroxime given as one double dose (1×3 g) or two single doses (2×1.5 g) with a four-hour interval.
METHODS
Sixteen pigs were randomized into two groups: Group 1 received one double dose of cefuroxime (1×3 g) as an intravenous bolus and Group 2 received two single doses of cefuroxime (2×1.5 g) as an intravenous bolus with a four-hour interval. Cefuroxime measurements were obtained from plasma, subcutaneous adipose tissue, vertebral cancellous bone, and intervertebral disc for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography. This work was supported by grants from the Health Research Foundation of Central Denmark Region (Level E). The funding source did not play any role in the investigation.
RESULTS
The time with concentrations above the Staphylococcus aureus clinical breakpoint minimal inhibitory concentration of 4 μg/mL was higher in all compartments for Group 2 compared to Group 1. The mean T>MIC (4 μg/mL) in all compartments ranged between 47% and 67% for Group 1 and 72% and 92% for Group 2. Furthermore, a delayed tissue penetration into all tissues for both groups was demonstrated.
CONCLUSIONS
This study suggests that cefuroxime should be given at least 45 minutes prior to spine procedures and as two single doses at a maximum interval of four hours for extended spine procedures. Clinical studies verifying these results are warranted.
CLINICAL SIGNIFICANCE
Administering cefuroxime as two single doses (2×1.5 g) with a four-hour interval compared to one double dose (1×3 g) resulted in higher T>MIC. Furthermore, we found delayed and incomplete cefuroxime tissue penetration.
Identifiants
pubmed: 32194245
pii: S1529-9430(20)30098-X
doi: 10.1016/j.spinee.2020.03.006
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
1327-1332Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.