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

• Published in: British journal of clinical pharmacology Vol. 84; no. 3; pp. 533 - 541
• Main Authors: Hansen, Kristian Kraft, Nielsen, Flemming, Stage, Tore Bjerregaard, Jørgensen, Uffe, Skov, Ole, Rasmussen, Lasse E.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.03.2018
• Subjects: Adipose Tissue - metabolism; Administration, Intravenous; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Area Under Curve; Chromatography, High Pressure Liquid; dicloxacillin; Dicloxacillin - administration & dosage; Dicloxacillin - pharmacokinetics; Humans; Male; Methods in Clinical Pharmacology; Microbial Sensitivity Tests; microdialysis; Microdialysis - methods; Muscle, Skeletal - metabolism; prophylactic antibiotics; Staphylococcus aureus - drug effects; Tissue Distribution; tissue pharmacokinetics; prophylactic antibiotics; dicloxacillin; microdialysis; tissue pharmacokinetics
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.13468

Aims The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. 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 analysed with high performance liquid chromatography (HPLC). Results The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. 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 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h 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 orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.