Distribution of systemically administered ampicillin, benzylpenicillin, and flucloxacillin in excisional wounds in diabetic and normal rats and effects of local topical vasodilator treatment

Abstract

The present study assessed the suitability of the streptozotocin-treated diabetic rat as a model for the study of diabetes-impaired wound healing. The distribution of three antibiotics, ampicillin, benzylpenicillin, and flucloxacillin, in wound and adjacent tissue sites on the abdomens and legs of normal and diabetic rats was determined 30 min after intravenous administration of a single bolus containing 50 mg of all three antibiotics per kg of body weight. Tissue/plasma ratios showed that antibiotic tissue penetration appeared to be related to protein binding. The treatment of wound sites with vasodilators (1% solution) to increase local blood flow and antibiotic delivery to the site was then determined and appeared to be more effective with endothelium-independent sodium nitroprusside than with endothelium-dependent acetylcholine in diabetic rats. These results suggest that coadministration of topical vasodilators to wound sites in neuropathic diabetic patients undergoing antibiotic therapy for infected ulcers could increase antibiotic delivery to wound tissue sites.