Factors affecting gentamicin penetration in lower extremity ischemic tissues with ulcers

Area of Science:

• Pharmacology
• Vascular Surgery
• Diabetology

Background:

• Foot ulcers are a common complication in patients with peripheral arterial disease (PAD) and diabetes.
• Effective antibiotic penetration is crucial for treating infections in these wounds.
• Gentamicin is frequently used, but its efficacy can be limited by tissue drug concentrations.

Purpose of the Study:

• To analyze gentamicin penetration in foot ulcers across varying severities of peripheral arterial disease (PAD).
• To identify factors influencing lower limb tissue concentrations of gentamicin.
• To guide optimal dosing strategies for gentamicin in patients with ischemic foot wounds.

Main Methods:

• Prospective study including 61 patients undergoing wound debridement or amputation.
• Intravenous gentamicin administration (120 mg or 240 mg) prior to intervention.
• Classification of patients based on PAD severity (nil/borderline, mild/moderate, severe).
• Measurement of gentamicin concentrations in serum and tissue samples using fluorescence polarization immunoassay.

Main Results:

• Gentamicin tissue concentration was significantly lower in patients with ischemic lower extremity wounds (mild to severe PAD) compared to non-ischemic wounds (P = .010).
• Female patients exhibited significantly lower gentamicin concentrations than male patients (P = .047).
• Tissue gentamicin levels were influenced by serum concentration, PAD severity, gender, and age.
• Subcutaneous tissue concentrations were approximately 0.663 times skeletal muscle concentrations (P < .00001).

Conclusions:

• Gentamicin penetration into foot ulcer tissues is reduced in patients with peripheral arterial disease (PAD).
• Factors such as PAD severity, female gender, and age impact gentamicin tissue distribution.
• Higher gentamicin doses may be necessary for patients with severe PAD to achieve therapeutic concentrations.
• Optimizing gentamicin dosing based on PAD severity and patient demographics is essential for effective treatment of diabetic foot infections.