Factors affecting gentamicin penetration in lower extremity ischemic tissues with ulcers

Abstract

The aims of the study were to analyze the penetration of gentamicin in foot ulcers in patients with different severities of peripheral arterial disease (PAD) and to determine significant parameters affecting lower limb tissue concentrations. Patients undergoing debridement of a wound or an amputation procedure were included. All patients received a 120 mg or 240 mg intravenous dose of gentamicin prior to the procedure. Patients were classified according to the degree of PAD. Tissue and serum samples were collected at the time of intervention, and gentamicin concentrations were determined by fluorescence polarization immunoassay. Blood and tissue samples were taken from 61 patients, 41 males and 20 females with a mean age of 66 years. Nineteen patients had nil or borderline PAD, 9 patients had mild or moderate PAD, and 26 patients had severe PAD. Forty-eight patients had type 2 diabetes, 8 patients had type 1 diabetes, and 5 patients were nondiabetic. The concentration of gentamicin in peripheral skeletal muscle tissue was dependent on the serum concentration, degree of PAD, gender, and age. For patients with ischemic lower extremity wounds (patients with mild, moderate, and severe PAD), the concentration of gentamicin was significantly lower (P = .010) than the concentration in nonischemic wounds, and the concentration in female patients was also significantly lower than in male patients (P = .047). The concentration in peripheral subcutaneous tissue was 0.663 times the concentration in skeletal muscle tissue (P < .00001). Gentamicin showed greatest penetration in male patients without PAD. For patients with severe PAD, higher doses of gentamicin may be required to achieve the same effect.