Flucloxacillin bone and soft tissue concentrations assessed by microdialysis in pigs after intravenous and oral administration

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Aims Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT > MIC) for methicillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model. Methods A total of 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every six hours during a 24-hour period. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin fT > MIC was evaluated using a low MIC target (0.5 μg/ml) and a high MIC target (2.0 μg/ml). Results Intravenous administration resulted in longer fT > MIC (0.5 μg/ml) compared to oral administration, except for cortical bone. In Group IV, all pigs reached a concentration of 0.5 μg/ml in all compartments. The mean fT > MIC (0.5 μg/ml) was 149 minutes (95% confidence interval (CI) 119 to 179; range 68 to 323) in subcutaneous tissue and 61 minutes (95% CI 29 to 94; range 0 to 121) to 106 minutes (95% CI 76 to 136; range 71 to 154) in bone tissue. In Group PO, 0/8 pigs reached a concentration of 0.5 μg/ml in all compartments. For the high MIC target (2.0 μg/ml), fT > MIC was close to zero minutes in both groups across compartments. conclusion Although intravenous administration of flucloxacillin 1 g provided higher fT > MIC for the low MIC target compared to oral administration, concentrations were surprisingly low, particularly for bone tissue. Achievement of sufficient bone and soft tissue flucloxacillin concentrations may require a dose increase or continuous administration.

OriginalsprogEngelsk
TidsskriftBone and Joint Research
Vol/bind10
Nummer1
Sider (fra-til)60-67
Antal sider8
ISSN2046-3758
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
We would like to acknowledge the financial support we have received, and the outstanding animal facilities and help available at the Department of Clinical Medicine at Aarhus University Hospital. We would also like to acknowledge Anette Baatrup at the Orthopaedic Research Lab, Aarhus, Denmark. The authors report institutional grants (paid to Aarhus University) from the Doctor Sofus Carl Emil Friis & Wife Olga Doris Friis' Fund and the Aase and Ejnar Danielsens Fund, related to this study. These were payments for conduction of the study (animals, analyses).M. A. F. Bendtsen reports a scholarship to conduct the study from the Novo Nordisk Foundation, grant number: NNF18OC0033304. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Publisher Copyright:
© 2021 Author(s) et al.

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

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