Double-dose cefuroxime concentrations in bone, synovial fluid of the knee joint and subcutaneous adipose tissue – A randomised porcine microdialysis study

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This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3000 mg (Group 1) or two single 15 min infusions of 1500 mg administered 4 h apart (Group 2). Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations (fT>MIC) of 4 μg/mL. The mean time fT>MIC (4 μg/mL) across compartments was longer for Group 2 (280–394 min) than for Group 1 (207–253 min) (p<0.01). Cortical bone showed a tendency towards longer fT>MIC (4 μg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p = 0.053). Within 50 min after administration, the mean concentration of 4 μg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 μg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero). During an 8 h interval, double-dose cefuroxime administered as 2 × 1500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 μg/mL) than a single bolus of 3000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re-administration of cefuroxime (1500 mg) should be considered 3 h after the first administration.

OriginalsprogEngelsk
Artikelnummer105754
TidsskriftEuropean Journal of Pharmaceutical Sciences
Vol/bind160
Antal sider6
ISSN0928-0987
DOI
StatusUdgivet - maj 2021

Bibliografisk note

Funding Information:
This work was supported by grants from the Augustinus Foundation, Kong Christian d. Tiendes Foundation, Læge Sofus Carl Emil Friis and Hustru Olga Doris Friis’ Legat, Familien Hede Nielsens Foundation, Torben and Alice Frimodts Foundation, Carl and Ellen Hertz’ Legat, Frimodt-Heineke Foundation, Christian Larsen and Dommer Ellen Larsens Foundation. For this financial support, we are very thankful. The funding sources did not play a role in the study.

Funding Information:
We thank the Department of Orthopaedic Surgery, Aarhus University Hospital and the Orthopaedic Research Unit, Aarhus University Hospital for supporting this study. We also thank biomedical laboratory scientist Anette Baatrup for her help with analyses. This work was supported by grants from the Augustinus Foundation, Kong Christian d. Tiendes Foundation, L?ge Sofus Carl Emil Friis and Hustru Olga Doris Friis? Legat, Familien Hede Nielsens Foundation, Torben and Alice Frimodts Foundation, Carl and Ellen Hertz? Legat, Frimodt-Heineke Foundation, Christian Larsen and Dommer Ellen Larsens Foundation. For this financial support, we are very thankful. The funding sources did not play a role in the study.

Publisher Copyright:
© 2021

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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