3 years ago

“Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man”

F. Nielsen, T.B. Stage, U. Jørgensen, L.E. Rasmussen, K.K. Hansen, O. Skov
Aim The most common pathogen in Denmark, to cause postoperative infections, is Staphylococcus (S.) aureus (1). Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. Methods MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analyzed with High Performance Liquid Chromatography. Results The maximum concentration was reached in muscle tissue after 0.5 hours and in adipose tissue after 0.8 hours. AUC0-6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 and a median of 4.1 hours in muscle tissue and a minimum of 1.8 and a median of 3.2 hours in adipose tissue. Conclusions The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopedic procedures. Whether this is true in patients with compromised circulation this remains to be investigated.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bcp.13468

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