Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis.
Animal model
Bone
Flucloxacillin
Infection
Spondylodiscitis
Journal
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
ISSN: 1432-0932
Titre abrégé: Eur Spine J
Pays: Germany
ID NLM: 9301980
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
03
03
2022
accepted:
05
04
2022
revised:
03
03
2022
pubmed:
30
4
2022
medline:
18
6
2022
entrez:
29
4
2022
Statut:
ppublish
Résumé
Flucloxacillin is a frequently used antibiotic in the treatment of spondylodiscitis. We assessed steady-state concentrations and time above minimal inhibitory concentration (fT > MIC) of flucloxacillin in the intervertebral disc, vertebral cancellous bone, subcutaneous tissue and plasma, after intravenous and oral administration. Sixteen pigs were randomized into two groups; Group Peroral (Group PO) and Group Intravenous (Group IV) received 1 g flucloxacillin every 6 h for 24 h orally or intravenously. Microdialysis was used for sampling in the compartments of interest. A flucloxacillin target of 50% fT > MIC was applied for three MIC targets: 0.125, 0.5 and 2.0 μg/mL. Intravenous administration resulted in significantly longer fT > MIC for all targets. Target attainment was only reached for the low target of 0.125 μg/mL in Group IV in vertebral cancellous bone, subcutaneous tissue, and plasma (intervertebral disc 47%). In Group IV, mean fT > MIC values in the investigated compartments were in the range of 47-67% of the dosing interval for 0.125 μg/mL, 20-35% for 0.5 μg/mL, and 0-15% for 2.0 μg/mL. In Group PO, mean fT > MIC values for 0.125 μg/mL were in the range of 1-33%. No pigs reached a concentration of 0.5 μg/mL in any of the investigated compartments in Group PO. Administration of 1 g flucloxacillin every 6 h resulted in surprisingly low steady-state fT > MIC after intravenous and oral administration. However, intravenous administration resulted in significantly higher concentrations across compartments compared to oral administration. Sufficient target tissue concentrations for treatment of spondylodiscitis may require a dose increase or alternative dosing regimens.
Identifiants
pubmed: 35488132
doi: 10.1007/s00586-022-07208-9
pii: 10.1007/s00586-022-07208-9
doi:
Substances chimiques
Anti-Bacterial Agents
0
Floxacillin
43B2M34G2V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1508-1514Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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