Flucloxacillin is conventionally administered intravenously for perioperative prophylaxis, while oral administration is typical for bacterial inoculation prophylaxis following smaller traumatic wounds. We aimed to assess the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT>MIC) for meticillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model.
16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every 6 h during 24 h. 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).
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 min in subcutaneous tissue and 61–106 min 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 0 min in both groups across compartments.
Although intravenous administration of flucloxacillin 1g 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.
The study was supported by the following grants: Sofus Carl Emil Friis Foundation, Aase & Ejnar Danielsens Foundation, the Augustinus Foundation, Direkt⊘r Emil Hertz og hustru Inger Hertz Foundation, and the Novo Nordisk Foundation.