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

Abstract

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.

Keywords

• flucloxacillin
• bone
• infection
• osteomyelitis
• animal model