Enhanced susceptibility to infections in a diabetic wound healing model

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.

Acute Primary Actinomycosis Involving the Hard Palate of a Diabetic Patient

“…It is believed that the high concentration of glucose in the wound fluid of patients with diabetes is the main reason for the increased bacterial growth seen in these patients. 5,12,13 According to Hirsch et al, 5 nondiabetic patients can resist bacterial invasion much more efficiently, whereas diabetic patients are more likely to succumb to the bacterial challenge. In addition, it is well known, although not completely understood, that diabetes mellitus impairs wound healing.…”

“…3 The chronic hyperglycemia of poorly controlled diabetes mellitus induces events that promote structural changes in various tissues and are associated with problems in wound healing and a greater susceptibility to infections. [4][5][6] Actinomycosis mimics different diseases and exhibits different symptoms, a fact that makes its diagnosis difficult. 3 Most commonly, it presents as a slowly progressive, indolent, indurated infiltration with multiple abscesses, fistulas, and sinuses.…”

Efficacy of Topically Delivered Moxifloxacin against Wound Infection by Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus

“…As a result, dramatic changes have occurred in the epidemiology of infections caused by MRSA in the last decade (25). In 2002, the first clinical isolate of vancomycin-resistant S. aureus (VRSA) was identified in patients with diabetic foot ulcers (12). Vancomycin, which is currently the most frequently used antibiotic in the treatment of severe MRSA infections, has become a suboptimal therapeutic agent in selected clinical settings (25).…”

Animal model «diabetic foot» on the background of experimental streptozotocin-i

“…К настоящему времени разработан ряд моделей эксперименталь-ного диабета [11], основными из которых являются: хирургическая (полное или ча-стичное удаление поджелудочной железы); химическая модель (используется введе-ние химических веществ, избирательно воздействующих на b-клетки островков: аллоксан, стрептозотоцин), генетические модели (получение трансгенных живот-ных). Моделирование «диабетической стопы», как правило, проводится на фоне стрептозотоцин-индуцированного диа-бета с принудительным инфицированием лапы Синегнойной палочкой (Pseudomonas aeruginosa) и Золотистым стафилококком (Staphylococcus aureus) [12,13].…”