Abstract
BackgroundWound infection is a common complication in diabetic patients. The progressive spread of infections and development of drug-resistant strains underline the need for further insights into bacterial behavior in the host in order to develop new therapeutic strategies. The aim of our study was to develop a large animal model suitable for monitoring the development and effect of bacterial infections in diabetic wounds.MethodsFourteen excisional wounds were created on the dorsum of diabetic and non-diabetic Yorkshire pigs and sealed with polyurethane chambers. Wounds were either inoculated with 2 × 108 Colony-Forming Units (CFU) of Staphylococcus aureus or injected with 0.9% sterile saline. Blood glucose was monitored daily, and wound fluid was collected for bacterial quantification and measurement of glucose concentration. Tissue biopsies for microbiological and histological analysis were performed at days 4, 8, and 12. Wounds were assessed for reepithelialization and wound contraction.ResultsDiabetic wounds showed a sustained significant infection (>105 CFU/g tissue) compared to non-diabetic wounds (p < 0.05) over the whole time course of the experiment. S. aureus-inoculated diabetic wounds showed tissue infection with up to 8 × 107 CFU/g wound tissue. Non-diabetic wounds showed high bacterial counts at day 4 followed by a decrease and no apparent infection at day 12. Epidermal healing in S. aureus-inoculated diabetic wounds showed a significant delay compared with non-inoculated diabetic wounds (59% versus 84%; p < 0.05) and were highly significant compared with healing in non-diabetic wounds (97%; p < 0.001).ConclusionDiabetic wounds developed significantly more sustained infection than non-diabetic wounds. S. aureus inoculation leads to invasive infection and significant wound healing delay and promotes invasive co-infection with endogenous bacteria. This novel wound healing model provides the opportunity to closely assess infections during diabetic wound healing and to monitor the effect of therapeutical agents in vivo.
Highlights
Wound infection is a common complication in diabetic patients
In diabetic animals non-inoculated wounds showed 350 mg/dl glucose concentration on day 1 post injury, a decrease to 79 mg/dl on day 8, and glucose was undetectable on day 12; whereas S. aureus-inoculated wounds showed no detectable glucose
Diabetic wounds showed 84 +/- 15%, and S. aureus-inoculated diabetic wounds were 59 +/- 8% reepithelialized. + = p < 0.05 diabetic versus non-diabetic wounds; * = p < 0.05 S. aureus-noculated diabetic versus non-inoculated diabetic wounds; # = p < 0.05 S. aureus-inoculated diabetic versus S. aureus-inoculated nondiabetic wounds; § = p < 0.001 S. aureus-inoculated diabetic wounds versus non-diabetic wounds
Summary
Wound infection is a common complication in diabetic patients. Wound infection is a major complication in diabetic patients[1]. Patients with diabetes have impaired wound healing associated with multitude of factors, including neuropathy, vascular disease, and foot deformities[3,4]. Patients with diabetes have impaired leukocyte function, and the metabolic abnormalities of diabetes lead to inadequate migration of neutrophils and macrophages to the wound, along with reduced chemotaxis[6,7]. Such cellular changes would predispose individuals to an increased risk of wound infection
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