Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
AIMS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
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 - 31(2022), 6 vom: 29. Juni, Seite 1508-1514 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bendtsen, Mathias A F [VerfasserIn] |
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| Links: |
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| Themen: |
43B2M34G2V |
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| Anmerkungen: |
Date Completed 17.06.2022 Date Revised 13.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00586-022-07208-9 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34016932X |
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| 041 | |a eng | ||
| 100 | 1 | |a Bendtsen, Mathias A F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 17.06.2022 | ||
| 500 | |a Date Revised 13.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a AIMS: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: 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 | ||
| 520 | |a CONCLUSION: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Animal model | |
| 650 | 4 | |a Bone | |
| 650 | 4 | |a Flucloxacillin | |
| 650 | 4 | |a Infection | |
| 650 | 4 | |a Spondylodiscitis | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Floxacillin |2 NLM | |
| 650 | 7 | |a 43B2M34G2V |2 NLM | |
| 700 | 1 | |a Hanberg, Pelle |e verfasserin |4 aut | |
| 700 | 1 | |a Slater, Josefine |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Jakob |e verfasserin |4 aut | |
| 700 | 1 | |a Öbrink-Hansen, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Stilling, Maiken |e verfasserin |4 aut | |
| 700 | 1 | |a Bue, Mats |e verfasserin |4 aut | |
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