Infection in diabetic foot ulceration; steps towards better knowledge for practice

People with diabetes can have up to a 25% lifetime risk of developing a DFU, largely because of diabetes related peripheral neuropathy and arterial disease, or both. Unless quickly diagnosed and treated, these diabetic foot ulcer infections can lead to substantial morbidity, including amputation; patients with a DFU that is infected have a 55-fold increased risk of hospitalisation, and a 154-fold increase in lower extremity amputation when compared to those with an uninfected DFU. Thus, any patient with a DFU has an assessment for symptoms or signs of infection at initial presentation and as well as at each subsequent visit. 

Current best practice recommends that this assessment includes a thorough history and physical examination to detect (or monitor) pain, tenderness, fever, purulent exudate, redness, warmth, induration, foul odour and visible or palpable bone. When infection of a DFU is suspected, practitioners take three actions: 1) obtain specimens from the ulcer for microbiological tests; 2) initiate protocol-based (usually broad-spectrum) empiric antibiotic therapy; and, 3) reassess the antibiotic regimen, and change if necessary, when the culture and susceptibility results are available. Previous systematic review of the performance of clinical assessment for the identification of infection did not confirm the power of individual clinical signs (in the diabetic foot ulcer population), and found no clear evidence regarding the optimal method for ulcer sampling, prompting research in this area.  

This presentation will describe the journey from questioning the methods of ‘identifying infection’ in diabetic foot ulcers by systematic review of the evidence base, through a large, HTA funded study of the agreement between ulcer sampling using tissue swabs and tissue samples, and describe planned work to test, for the first time, the impact of sampling methods upon clinical management and clinical outcomes in a large randomised trial.  It will also describe the way in which research is assessing both potential benefits and pitfalls associated with molecular testing techniques, which use genetic fingerprints of bacterial DNA, rather than growing bacteria in the laboratory / on a Petri dish, to determine the bacterial growth in an ulcer. 

This work is intended to ultimately provide clinicians with better information to tailor the antibiotics prescribed (and their duration) using different sampling or processing techniques, whilst avoiding both under treatment with potential impact on ulcer healing, and over-treatment, with associated increase in antimicrobial resistance in bacteria – a catastrophic threat to health. 

Three points: 
1. 1 in 4 people with diabetes will develop a foot ulcer, most of which are infected. This infection may delay healing and cause more damage to the foot, and spread further. It is important to balance between the risks of over-treatment and under-treatment with antibiotics, to ensure antibiotic resistance doesn’t increase. The ways we assess foot ulcer for infection haven’t previously been tested in large, reliable studies to see if the signs of infection are fool-proof. 

2. Until recently we haven’t had robust evidence to guide clinicians in how to collect samples for the microbiology laboratory, for example tissue swab, or piece of ulcer tissue. Research performed by our team has established the differences between tissue sampling and swabbing foot ulcers for microbiology, demonstrating the increased information obtained from tissue samples over swabs. 

3. We are now planning to investigate whether increased information on the bacteria in a wound makes any impact on management and clinical outcomes. We are also looking at the potential for genetic fingerprinting of bacteria to replace traditional culture techniques, using virtual clinics and qualitative methods. 
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