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.

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study

“…For example, Zammit et al [38] have investigated the impact of increasing severity of PAD on the tissue concentration of gentamicin in patients with ischemic ulcers. These authors have found a strong inverse correlation between PAD severity and local limb tissue concentration of the antibiotic drug, suggesting that local blood flow regulation is an important determinant of drug efficacy.…”

Daptomycin-Nonsusceptible Staphylococcus aureus: The Role of Combination Therapy with Daptomycin and Gentamicin

“…The concentration of gentamicin in skeletal muscle and subcutaneous tissue varies depending on gentamicin concentration in serum, gender, age, the degree of peripheral arterial disease and pathological state of the tissue [ 33 , 34 , 35 ]. A range between 0.3 μg/mL and 7 μg/mL gentamicin in skeletal muscle and tissue was reported in the literature after a 3 mg/kg/day dose [ 33 , 34 , 35 , 36 ]. To simulate a low gentamicin concentration in deep-seated infection, a gentamicin dose of 0.25 μg/mL or 0.5 μg/mL (0.5× MIC) was used in time-kill analyses.…”

Factors Affecting Penetration of Ciprofloxacin in Lower Extremity Ischemic Tissues

“…The concentration of ciprofloxacin in the subcutaneous tissue of this group of patients is related to the concentration of ciprofloxacin in plasma, the number of medications that the patients are taking and also on the severity of PAD. In a similar study conducted by Zammit et al 34 using gentamicin as the anti-infective agent of interest, gentamicin tissue concentrations were found to mostly depend on gender and degree of PAD severity.…”

“…There have been similar studies documenting the determination of other anti-infective agents in the tissue of patients suffering from PAD. 33,34 However, the distribution of ciprofloxacin in patients suffering from diabetic foot ulcers with varying degrees of PAD is not known and is being investigated in this study.…”