Phage therapy for diabetic foot infection

Matthew J Young, Lesley ML Hall and Joshua D Jones

      The treatment of diabetic foot infections (DFIs) represents a costly and growing challenge to the NHS. DFIs can be difficult to treat for a variety of reasons, including late presentation of advanced infection, and antibiotic tolerance or resistance. Bacteriophage (phage) are ubiquitous viruses that infect and kill bacteria in a species-, sometimes even strain-, specific manner. Phages have been used to treat bacterial infection since 1919, but their use in the geopolitical West ceased in the 1930s due to a variety of factors, including the mass production of antibiotics. The modern antibiotic resistance crisis has driven renewed interest in phage therapy and 2,241 patients with mostly with antibiotic refractory infections have been treated since 2000, 79% of whom improved. This includes at least 310 patients with chronic wound infections, among whom 86.1% achieved clinical resolution or improvement of infection. Reassuringly, the available evidence suggests that phage therapy is safe and without notable side effects. Some phages also possess enzymes capable of degrading the biofilms that afford antibiotic tolerance to bacteria and underpin many chronic infections. Phages also act independent of antibiotic resistance, allowing the treatment of even pan-resistant bacteria, and topical or local application to DFIs means antimicrobial activity is independent of a patient’s peripheral perfusion. Presently only an option when antibiotics are not meeting a patient’s clinical needs, future integration of phage therapy at all levels of DFI care will radically transform the outlook for DFIs in the UK. Reducing the number of serious infections and amputations will not only benefit patients but will deliver vast savings to the NHS and reduce the amount of antibiotics used, making phage therapy a tangible response to the antibiotic resistance crisis.

Citation: Young MJ, Hall LML, Jones JD (2022) Phage therapy for diabetic foot infection. The Diabetic Foot Journal 25(4): 30–7

Key words - Bacteriophage  - Diabetic foot infection  - Phage therapy

Article points

1. Bacteriophages (phages) are viruses that infect and kill bacteria that can be used to treat infections, known as phage therapy.

2. The available evidence suggests that phage therapy is safe and effective for the treatment of wound infections.

3. Phage therapy has the potential to transform the care of diabetic foot infections.

Authors

      Matthew J. Young is Consultant Physician, Royal Infirmary of Edinburgh, Edinburgh, UK; Lesley ML Hall is Consultant Physician, Diabetes and Endocrinology, Queen Elizabeth University Hospital, Glasgow, UK; Joshua D Jones is Consultant Physician, Infection Medicine, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, UK; Clinical Microbiology, Ninewells Hospital, NHS Tayside, Dundee, UK

Early-onset type 2 diabetes: Clinical implications, diagnosis and management

David Morris

There is strong evidence that early-onset type 2 diabetes (commonly defined as that occurring in people under the age of 40 years) is a more aggressive condition than late-onset type 2 diabetes. The longer period of exposure to the risk factors of hyperglycaemia, hypertension and hyperlipidaemia and the more rapid progression of disease itself renders the individual more vulnerable to developing both microvascular and macrovascular complications at an earlier age. Early recognition and management of type 2 diabetes in younger people and public health messaging aimed at prevention of type 2 diabetes will be crucial to dealing with the problem. This article outlines the diagnosis, clinical implications and management of early-onset type 2 diabetes, with a particular focus on younger adults (rather than children and adolescents), in whom the condition is more common, and who are likely to be managed in primary care.

Citation: Morris D (2022) Early-onset type 2 diabetes: Clinical implications, diagnosis and management. Journal of Diabetes Nursing 26: [Early view publication]

Article points

Article points

1. The incidence of early-onset type 2 diabetes is increasing, with important individual health and socioeconomic consequences.

2. Individuals with early-onset type 2 diabetes experience more rapid progression of microvascular and cardiovascular complications than those with type 1 diabetes and those who develop type 2 diabetes in later years.

3. The presence of islet cell autoantibodies is predictive of future insulin requirement and the development of other autoimmune diseases.

4. If there is uncertainty about the type of diabetes in a child or young adult, it is safer to manage as type 1 diabetes and treat with insulin.

5. A holistic approach to earlyonset type 2 diabetes is essential. Socioeconomic status and psychological issues need to be taken into account.

Key words

- Children and young people - Early-onset type 2 diabetes

Author

David Morris, Specialist Doctor in Diabetes, Royal Shrewsbury Hospital; Clinical Undergraduate Tutor, Keele University; and retired GP

Depression — the ‘elephant in the room’ for the under-utilisation of foot self-care in diabetes?

Andrew Hill

      Much evidence indicates that foot self-care behaviours, specifically, remain underutilised in the prevention of diabetic foot ulcers (DFUs). Adherence to care is a multidimensional phenomenon, determined by the interplay of several factors, including: social and economic, patient-related, health-system-related and conditionrelated factors. Of particular interest and relevance may be the role that depression plays in the context of foot self-care in diabetes, which is discussed in this article. Diabetes-associated depression is well established phenomenon and the prevalence of depression amongst people with diabetes is known to be in the range of 10%–15% — which is twice the rate of people without diabetes. Furthermore, the outcomes for diabetes and depression are worse when they appear together. The mechanisms of their co-existence are multiple and complex and likely involve sociological, psychological and physiological elements. Their co-existence also appears to heavily influence the likelihood of individuals to undertake self-care behaviour that may help to avert the worst of the diabetes-related complications, such as DFU and amputation

Citation: Hill A (2022) Depression — the ‘elephant in the room’ for the under-utilisation of foot self-care in diabetes. The Diabetic Foot Journal 25(4): 16–21

Key words

- Foot care practices - Patient and public involvement - Risk identification - Risk reduction

Article points

1. Adherence to foot selfcare behaviours is a multidimensional phenomenon, determined by the interplay of several factors, including: social and economic, patient related, health-system-related, and condition-related.

2. Depression is well known to co-exist in many people with diabetes — especially those who have suffered diabetesrelated complications, such a foot ulceration and amputation.

3. The co-existence of diabetes and depression appears to heavily influence the likelihood of individuals to undertake self-care behaviour that may help to avert the worst of the diabetes-related complications, such as DFU and amputation.

Authors

Andrew Hill is Senior Lecturer and Programme Lead, The SMAE Institute, Maidenhead, UK

CGM for children and young people with type 1 diabetes: NICE criteria and effects of decision fatigue and alarm fatigue

Imogen Stamford

Research has shown that use of continuous glucose monitoring (CGM) is associated with improved time in range, improved HbA1c, and decreased risk of long-term complications secondary to type 1 diabetes. There are, however, several barriers that can lead to discontinuation of CGM, including pain, skin reactions, concerns around accuracy, sensor loss, interference with daily activity, and alarm fatigue. This review paper will outline the impact of decision fatigue and alarm fatigue in children and young people using CGM.

Citation: Stamford I (2022) CGM for children and young people with type 1 diabetes: NICE criteria and effects of decision fatigue and alarm fatigue. Diabetes Care for Children & Young People 12: [Early view publication]

Article points

1. While the advantages of continuous glucose monitoring (CGM) are well recognised, as practitioners it is important to be aware of the implications of CGM use.

2. People with diabetes can never have a day without checking and responding to ever-changing glucose levels, which puts them at an increased risk of developing decision fatigue.

3. It is important for practitioners to support patients in creating balance between setting alarm limits that are narrow enough to ensure patient safety, but not so narrow that alarms will be repeatedly triggered can lead to the risk of alarms being ignored.

Key words

- Alarm fatigue - Continuous glucose monitoring - Decision fatigue - Type 1 diabetes

Author

Imogen Stamford, Paediatric Diabetes Specialist Nurse, Oxford University Hospitals NHS Foundation Trust

The Wound Microbiome

Ellen K. White and Elizabeth A. Grice

Department of Dermatology, University of Pennsylvania, Perelman School of Medicine, Philadelphia,

Pennsylvania 19104, USA

Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

      Breach of the skin barrier and subsequent wound healing occur in the context of microbial communities of bacteria, fungi, and viruses. These polymicrobial communities are dynamic and important components of the wound environment and are associated with differential healing outcomes. Here, we highlight both culture-dependent and -independent methods that have furthered our understanding of the wound microbiome. We discuss common themes that have developed from such studies about the microbial inhabitants of diverse wound types.We additionally explore the wide range of microbial mechanisms that influence healing, from invading pathogens to beneficial commensals. These insights can be leveraged to better predict healing outcomes and derive novel microbial-based therapies for chronic wounds.

Editors: Xing Dai, Sabine Werner, Cheng-Ming Chuong, and Maksim Plikus Additional Perspectives on Wound Healing: From Bench to Bedside available at www.cshperspectives.org Copyright © 2022 Cold Spring Harbor Laboratory Press; all rights reserved Advanced Online Article. Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a041218

Role of wound microbiome, strategies of microbiota delivery system and clinical management

Qinghan Tang a,1 , Nannan Xue a,b,1 , Xiaofeng Ding c,d , Kevin H.-Y. Tsai e , Jonathan J. Hew f , Ruihan Jiang a ,

Rizhong Huang a , Xuxi Cheng a , Xiaotong Ding a , Yuen Yee Cheng g , Jun Chen a,b,⇑ , Yiwei Wang a,b,e,⇑

a Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing 210023, PR China

b Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China

c Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China

d Department of Plastic Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, PR China

e Burns and Reconstructive Surgery Group, ANZAC Research Institute, Concord Hospital, The University of Sydney, Concord West, NSW 2137, Australia

f General Surgery, Lesimore Hospital, NSW 2480, Australia

g Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, University of Technology Sydney, NSW 2007 Australia

abstract

      Delayed wound healing is one of the most global public health threats affecting nearly 100 million people each year, particularly the chronic wounds. Many confounding factors such as aging, diabetic disease, medication, peripheral neuropathy, immunocompromises or arterial and venous insuffificiency hyperglycaemia are considered to inhibit wound healing. Therapeutic approaches for slow wound healing include anti-infection, debridement and the use of various wound dressings. However, the current clinical outcomes are still unsatisfified. In this review, we discuss the role of skin and wound commensal microbiota in the different healing stages, including inflflammation, cell proliferation, re-epithelialization and remodelling phase, followed by multiple immune cell responses to commensal microbiota. Current clinical management in treating surgical wounds and chronic wounds was also reviewed together with potential controlled delivery systems which may be utilized in the future for the topical administration of probiotics and microbiomes. This review aims to introduce advances, novel strategies, and pioneer ideas in regulating the wound microbiome and the design of controlled delivery systems.

article info

Article history:

Received 27 September 2022 Revised 23 November 2022 Accepted 14 December 2022 Available online 17 December 2022

Keywords:

Wound healing，Skin microbiome，Inflammation，Clinical wound care，Cell response to microbiome，Probiotic delivery

Abbreviations: 16S-rDNA, 16S ribosomal DNA identifification; b2-AR, b2-adrenergic receptor; ADAM10, A disintegrin and metalloprotease 10; AHR, aryl hydrocarbon receptor; AMP, adenosine monophosphate; B. subtilis, Bacillus subtilis; C. albicans, Candida albicans; CSF, colony-stimulating factor; CXCL2, chemokine (C-X-C motif) ligand 2; CXCL10, chemokine (C-X-C motif) ligand 10; CXCL12, chemokine (C-X-C motif) ligand 12; DFU, diabetic foot ulcer; ECM, extracellular matrix; E. coli, Escherichia coli; EPB, epidermal permeability barrier; EVs, extracellular vesicles; FDA, Food and Drug Administration; hBD, human b-defensin; HF, Hair follicle; HMP, Human Microbiome Project; IL-1, interleukin-1; IL-1R, interleukin-1R; IL-1b, interleukin-1b; IL-6, interleukin-6; IL-23, interleukin-23; K. pneumoniae, Klebsiella pneumoniae; L. acidophilus, Lactobacillus acidophilus; L. lactis, Lactococcus lactis; L. plantarum, Lactobacillus plantarum; L. reuteri, Lactobacillus reuteri; L. rhamnosus, Lactobacillus rhamnosus; M
CSF, macrophage colonystimulating factor; MHCII, major histocompatibility complex II; MMP-9, matrix metalloproteinase-9; MRSA, methicillin-resistant Staphylococcus aureus; MYD88, myeloid differentiation factor 88; NETs, neutrophil extracellular traps; NIH, National Institutes of Health; NPWT, negative pressure wound therapy; P. aeruginosa, Pseudomonas aeruginosa; pDCs, plasmacytoid dendritic cells; PEO, polyethylene oxide; PLA, polylactic acid; ROS, reactive oxygen species; PRP, Plat-rich plasma; PVA, polyvinyl alcohol; PVP, polyvinyl pyrrolidone; SadA, serum adenosine deaminase; S. aureus, Staphylococcus aureus; Sbi, staphylococcal immunoglobulin-binding protein; SCMC, sodium carboxymethylcellulose; S. epidermidis, Staphylococcus epidermidis; SLO, streptolysin O; SpA, Staphylococcal protein A; SPF, specifific pathogen-free; SSWI, surgical site wound infection; TAs, trace amines; Tc17, cytotoxic T cells 17; TGF-b1, transforming growth factor-b1; TNF-a, tumor necrosis factor-a; VEGF, vascular endothelial growth factor; WHO, World Health Organisation. ⇑ Corresponding authors at: Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, PR China. E-mail addresses: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。, 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J. Chen), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y. Wang). 1 These authors contributed equally to these work.

https://doi.org/10.1016/j.addr.2022.114671 0169-409X/
2022 Published by Elsevier B.V.