Exploring the microbiome & antibiotic resistance in chronic wounds
Research type
Research Study
Full title
Exploring the microbiome & antibiotic resistance in chronic wounds using advanced sequencing (Nanopore) methods
IRAS ID
300733
Contact name
Angela Oates
Contact email
Sponsor organisation
University of Hull
Clinicaltrials.gov Identifier
RS158, University of Hull (Sponsor)
Duration of Study in the UK
1 years, 11 months, 31 days
Research summary
Delayed wound healing is a common occurrence in chronic wounds often resulting in a reduced quality of life for patients. Infection can be a key factor in this delayed healing. The presence of antimicrobial resistance in bacteria (pathogens that have developed ways which stop antibiotics from working) often make treating the infection difficult. This results in treatment failures, prolonging the infection and further delaying healing.
Chronic wounds can harbour a range of microorganisms, together termed the microbiome. This microbiome represents the whole microbial community of the wound and can be composed of different types of bacteria including those that can cause infections and also those which are part of the normal organisms present on the skin. Each member of this community can have variable types of antibiotic resistance. The resistome of this community refers to the antibiotic resistance profile (all antibiotic resistance genes) of the whole bacterial community in the wound.
This project aims to explore the wound microbiome and resistome of chronic wound infections and see how these communities and antibiotic resistance change during infection and antibiotic treatment. We will use advanced DNA sequencing-based approaches to identify the microbiome and their antibiotic resistance profiles using non-invasive swab samples from infected wounds.
This project will involve participants that have a clinical diagnosis of a wound infection requiring a routine sample for microbiology investigations and associated antibiotic recommendations. After samples are collected for microbiology, we will take one extra swab sample in this study (the baseline sample). At routine weekly clinical follow up visits, we will take one additional swab each week for 4 weeks from the first baseline swab collection. This will be an important first step in understanding how the microbiome in wound infections react to antibiotic treatment regimens and the impact on wound healing rates.
Lay Summary of Results:
What was this study about?
This study, funded by a University of Hull PhD Scholarship, explored the microorganisms (microbiome) and antibiotic resistance in chronic wounds, specifically diabetic foot ulcers (DFUs). Chronic wounds often heal slowly and can severely affect the quality of life. One of the main reasons for delayed healing is infection, especially when bacteria are resistant to antibiotics, making treatment less effective and further complicating the healing process.Why is this important?
Chronic wounds are home to diverse microorganisms, collectively called the microbiome. Some of these microorganisms are harmful and can cause infections that are difficult to treat, particularly when they develop resistance to antibiotics. Understanding which microorganisms are present and their antibiotic resistance patterns can help improve treatments, prevent complications like sepsis or amputation, and ultimately support faster healing.What did we aim to do?
The study aimed to identify the microbial community in DFUs, track how this changes during treatment, and investigate patterns of antibiotic resistance over time. This could improve understanding of the relationship between microbial behaviour and wound healing.Who participated?
The study recruited nine participants from a single foot clinic. These were individuals who consented to take part and had chronic diabetic foot ulcers with active infections. The research team collected wound swab samples weekly over five weeks. During this time, the clinical team monitored the wounds and managed treatments, including wound size measurements, dressings used, antibiotics prescribed, and clinical diagnoses of pathogens.What did we do in the laboratory?
In the laboratory, DNA was extracted from microorganisms in the wound swabs. Using PromethION Nanopore sequencing technology, we analysed the DNA to identify the microorganisms present in each sample and their relative abundances. This approach allowed us to detect a wide range of bacteria, including those that are difficult or impossible to grow using traditional laboratory methods.What did we find?
1. Microorganisms in wounds
The diabetic foot ulcer microbiomes contained various microorganisms. Common wound pathogens, like Staphylococcus aureus, were frequently identified. However, some less well-known microorganisms were also found in significant amounts. For example, Corynebacterium striatum and Finegoldia magna (two types of bacteria) were the most abundant bacterial species in this group of participants. These microbes are often overlooked in clinical diagnoses because they are difficult to grow or are considered harmless when detected in low amounts.
2. Limitations of traditional methods
When diagnosing infections, clinical labs often rely on culturing (growing) bacteria from patient samples. While this method works well for some microbes, it misses others that are difficult to grow in a lab or are present in small quantities. For example, in one sample, the clinical diagnosis did not report the presence of Pseudomonas aeruginosa, a key wound pathogen. However, DNA sequencing identified it at a low abundance. Over subsequent weeks, this bacterium became the dominant organism in that wound. Finegoldia magna, an anaerobic bacterium (which thrives in environments without oxygen), is challenging to grow due to competition from other bacteria. Despite this, sequencing detected it reliably in several samples.
3. Antibiotic resistance
Using sequencing, we identified genes linked to resistance against at least 12 different classes of antibiotics. These included resistance to common first-line antibiotics like flucloxacillin, doxycycline, and clarithromycin. This finding is significant as it highlights the potential for treatment failures and the need to develop new approaches to manage such infections.
4. Changes in the microbiome over time
The study revealed that the microbial community in wounds is dynamic. Microorganisms and their abundances changed over the five weeks, influenced by the treatments provided. For example, some bacteria increased in abundance despite antibiotic treatment, while others became less prominent.What do these results tell us?
This study shows the potential of DNA sequencing to improve the diagnosis and treatment of wound infections. Unlike traditional culture methods, sequencing can quickly identify a broader range of microorganisms, including those that are hard to grow in the lab. It also provides insights into antibiotic resistance and changes in the microbiome over time. While this study included a small number of participants, it offers important findings that could guide future research and improve care for patients with chronic wounds.REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
21/YH/0272
Date of REC Opinion
14 Dec 2021
REC opinion
Further Information Favourable Opinion