Mathias A F Bendtsen1,2,3, Pelle Hanberg4,5,6, Josefine Slater4,5,7, Jakob Hansen4,8, Kristina Öbrink-Hansen4,9, Maiken Stilling4,5,7, Mats Bue4,5,7. 1. Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark. m.bendtsen@clin.au.dk. 2. Aarhus Microdialysis Research Group, Aarhus University Hospital, Aarhus, Denmark. m.bendtsen@clin.au.dk. 3. Department of Orthopedic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus, Denmark. m.bendtsen@clin.au.dk. 4. Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark. 5. Aarhus Microdialysis Research Group, Aarhus University Hospital, Aarhus, Denmark. 6. Department of Orthopedic Surgery, Horsens Regional Hospital, Horsens, Denmark. 7. Department of Orthopedic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus, Denmark. 8. Institute of Forensic Medicine, Aarhus University, Aarhus, Denmark. 9. Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Abstract
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.
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.
Authors: Mats Bue; Pelle Hanberg; Janne Koch; Louise Kruse Jensen; Martin Lundorff; Bent Aalbaek; Henrik Elvang Jensen; Kjeld Søballe; Mikkel Tøttrup Journal: J Orthop Res Date: 2017-11-22 Impact factor: 3.494