Pharmacokinetics of double-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone - A randomized microdialysis study

TY - JOUR

T1 - Pharmacokinetics of double-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone - A randomized microdialysis study

AU - Hanberg, Pelle

AU - Bue, Mats

AU - Jørgensen, Andrea René

AU - Thomassen, Maja

AU - Öbrink-Hansen, Kristina

AU - Søballe, Kjeld

AU - Stilling, Maiken

N1 - Copyright © 2020. Published by Elsevier Inc.

PY - 2020/8

Y1 - 2020/8

N2 - 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 2-3 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.METHOD: 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 (Amount: 70.000 dollars). 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 with Group 1. The mean T>MIC (4 μg/mL) in all compartments ranged between 47%-67% for Group 1 and 72%-92% for Group 2. Furthermore, a delayed tissue penetration into all tissues for both groups was demonstrated.CONCLUSION: This study suggests that cefuroxime should be given at least 45 min 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 with one double dose (1 × 3 g) resulted in higher T>MIC. Furthermore, we found delayed and incomplete cefuroxime tissue penetration.

AB - 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 2-3 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.METHOD: 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 (Amount: 70.000 dollars). 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 with Group 1. The mean T>MIC (4 μg/mL) in all compartments ranged between 47%-67% for Group 1 and 72%-92% for Group 2. Furthermore, a delayed tissue penetration into all tissues for both groups was demonstrated.CONCLUSION: This study suggests that cefuroxime should be given at least 45 min 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 with one double dose (1 × 3 g) resulted in higher T>MIC. Furthermore, we found delayed and incomplete cefuroxime tissue penetration.

KW - Cefuroxime

KW - Intervertebral disc

KW - Microdialysis

KW - Pharmacokinetics

KW - Tissue penetration

KW - Vertebra

U2 - 10.1016/j.spinee.2020.03.006

DO - 10.1016/j.spinee.2020.03.006

M3 - Journal article

C2 - 32194245

SN - 1529-9430

VL - 20

SP - 1327

EP - 1332

JO - The spine journal : official journal of the North American Spine Society

JF - The spine journal : official journal of the North American Spine Society

IS - 8

ER -