Modelling polymicrobial infection of diabetic foot ulcers in vitro
Research type
Research Study
Full title
Modelling polymicrobial infection of diabetic foot ulcers in vitro
IRAS ID
217101
Contact name
Bianca Price
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
0 years, 5 months, 22 days
Research summary
Research Summary
This study proposes to collect debrided tissue from up to ten patients who have a superficial diabetic foot ulcer (DFU) that is infected, designated grade 1B. Tissue will be collected from patients on the day that they present with a grade 1B ulcer and then again after a week of treatment with antibiotics.
Tissue will be imaged using microscopy in order to compare it to the wound model that we have developed in the laboratory. The wound model is composed of a matrix in which human cells are grown that aims to mimic the dermis. Some tissue will also be homogenised in order to harvest the bacteria in the foot ulcer. These bacteria will be added to the wound model in order to represent a diabetic foot ulcer infection in the lab. Once the bacteria have grown into a biofilm, Stimulan beads loaded with antibiotics (Biocomposties Ltd, UK) will be added to the wound to assess the efficacy of antibiotics released from the beads against the biofilm.
We will follow patients up after a week of treatment with antibiotics. We will again collect debrided tissue. This tissue will be homogenised and a sample will be sent to the antibiotic reference lab to measure the concentration of antibiotics in the tissue near the wound. We will again harvest bacteria and compare the type and number of bacteria harvested after a week of treatment to those harvested before treatment.
These data will allow us to assess the effect of antibiotics prescribed to patients with DFUs on the wounds directly. They will also be used to verify whether the laboratory model of diabetic foot infection compares to a real DFU. Finally we will look at the effect of antibiotics released from Stimulan beads on bacteria that are relevant to diabetic foot infection.
Summary of Results
Diabetic foot ulcers are common in patients with diabetes, and can frequently fail to heal despite antibiotic treatment delivered by the normal route to the whole body (systemic antibiotics). This study developed a lab proxy for foot ulcers, using gels formed from collagen, a constituent of normal tissues. This enabled a comparison of the antibacterial activity of normal levels of systemic antibiotics with that for antibiotics released from calcium sulfate beads, a alternative way to deliver antibiotics directly to the infected tissues. The clinical work enabled harvesting bacteria from diabetic foot infections and these were provided as similar polymicrobial biofilms to those present in real patients. The results were that there was a small decrease in living bacteria with systemic antibiotics, but a massive reduction in live bacteria in the model after treatment locally. Systemically administered antibiotics are likely to be inadequate for successfully treating these infections, and topical antibiotics provide a more effective alternative. See: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQne05VVe0UaW9iiRd6kqFohGCKzKnzOh04P8-2BOstcQwkZhYCXbeVVG3iAdBQRwGPg-3D-3DFYxv_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJhicBankpAZ7fZ8hHuGYW-2BVz3C5BGevX1jShv9TX-2Fr4Yd9-2B7WmR3Q1l8TbF-2BQCxu-2FhVpsvwyXuWzu5-2BrlzwLubwbpvrG0cl-2FPY4QnMHqJfupI0Z2OX3oKax6bFKpRsKw3ImJjD30eaIKBXMDZTme0a9Cb4zAFAZ-2B-2FGRN0tMxDsmg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C76faa4dc369a419709c408da5de0a437%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637925516647167382%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=6i999TFoV8Zs5vcl3QR06KY%2FdLM2z3Ra0E9CNq3do6Q%3D&reserved=0
REC name
London - Fulham Research Ethics Committee
REC reference
17/LO/0123
Date of REC Opinion
18 Jan 2017
REC opinion
Favourable Opinion