Background

Delayed healing of chronic wounds places a burden on individuals, especially those at high risk, such as patients with SCI, and healthcare systems. It leads to significant discomfort, distress and morbidity to patients. In the UK, there are approximately 2.2 million wounds per annum, costing £5.3 billion a year, of which over a third are chronic.5

The microbiome of the skin interacts, and is synergistic with, the immune system. A healthy microbiome is diverse, balanced and constantly changes in response to factors such as environment, health and hygiene.5 A microbiome lacking diversity, as a result of indiscriminate or inappropriate use of antiseptics and antibiotics, is at risk of infection, especially if one or two species of bacteria begin to dominate.8 Chronic wounds are often caused by persistent or recurrent infection, prolonged by the action of a biofilm nullifying effective treatment.

The formation of a biofilm leads to continued infection and delayed healing. Biofilms are made up of communities of microorganisms, protected by an extracellular matrix of slime in the wound, created during the chronic phase of a wound. This barrier can tolerate the host immune defenses and applied topical antimicrobials and therefore make the treatment of such wounds very challenging.9

The current methods of wound treatment, using dressings (including antimicrobial, silver or honey), antiseptic washes and antimicrobial powders, have a poor evidence base and are potentially detrimental to the host immune system while leading to cytotoxic effects and antimicrobial resistance.3 5

Furthermore, patients who have sustained a SCI are more likely to develop chronic wounds as a result of SCI-induced immune depression syndrome (SCI-IDS).10 SCI-IDS, caused by loss of neuronal regulation of the immune system below the injury, results in a reduction in the ability to combat infection, delays wound healing and therefore increases the propensity of minor wounds, such as a pressure sore, developing into large, non-healing wounds.10

Case study

A Service Person in his 30s sustained a complete SCI in 2016. In early 2019, he developed an abscess, requiring incision and drainage. It was packed with Sorbsan ribbon and covered with secondary dressings and began to heal with high levels of wound exudate. In discussion with the plastic surgeons, a further surgical procedure was performed for wound closure in June.

Post surgery, a haematoma formed followed by the wound spontaneously fully reopening. Topical negative pressure wound treatment (TNPWT) was commenced as a second-line treatment. By September, a chronic wound had developed which continued to fail to heal, and the TNPWT was stopped. The wound was subsequently managed with Aquacel ribbon packing, covered with Tegaderm foam or Tielle Lite as a secondary dressing to manage a large amount of exudate. Input was also sought from wound care specialists to assist the nursing staff.

These treatment regimes were unfortunately unsuccessful in wound healing and failed to manage the amount of wound exudate or the strong associated odour. The chronicity of the wound, especially the smell, impacted negatively on the psychological well-being and physical rehabilitation of the patient. He required increased bed rest, reducing his time in the wheelchair, and leading to a dramatic loss of independence.

The patient was offered a trial of Amicapsil therapy commencing in October 2019 (Figure 1). This was initially a twice-daily, non-sterile procedure, with Amicapsil applied by a nurse, after the wound was cleaned with tap water, in the morning and evening. During the application of Amicapsil, the vial was sprinkled over the wound, coating the wound surface and surrounding areas with a thin layer of the powder. After application of Amicapsil, the wound would ideally be left open to air, but if needed for rehabilitation purposes, a thin lint-free gauze, allowing airflow, was applied to manage exudate.

The wound was reviewed daily by nursing staff, weekly on the consultant ward round, and photographs were taken at regular intervals to provide a record of changes in the wound size, shape and exudate production. As part of the trial, representatives of Willingsford also monitored the wound remotely via emails with the patient.

After the first 4 weeks, there was a dramatic improvement in the wound with dimensions and exudate levels substantially reduced and epithelisation visible (Figure 2). Within a week of starting, the wound odour had disappeared. As a result of this improvement, the patient was happy to continue with the trial, especially as the use of an air pump into the gauze dressing allowed wound healing to continue while having the extended periods in his wheelchair. As the wound continued to improve, Amicapsil administration decreased to once daily (Figure 3).

After 3 months, there was a minimal residual open area to the wound with a very low exudate level (Figure 4), and by 6 months, full resolution of the wound was nearly reached with the wound in the remodelling stage (Figure 5). The patient encountered no adverse effects as a result of his Amicapsil therapy.

What is MPPT and how does it work?

Amicapsil is the first MPPT product licensed for clinical use by the Food and Drug Administration. It is an inactive, neutral white powder, applied by hand and requires a constant flow of air once applied.5 It works in conjunction with the host immune system by disrupting the wound biofilm and helping restore the microbiome. This action occurs by penetrating and perforating the biofilm surface, and allowing the host immune cells (including macrophages, neutrophils and other cells of the inflammatory response) to infiltrate the chronically colonised wound.5

The Amicapsil particles draw moisture up through capillary action (mimicking leukotriene action), drawing the excess fluid up and allowing it to evaporate, hence the need for airflow over the wound site in order to maintain capillary action.5 Once the inflammatory response has cleared the colonised bacteria, then microbiome rebalancing can occur.

The introduction of neutrophils and macrophages into the wound retriggers the inflammatory phase of wound healing. The former is indicated in chemosignalling, vascular permeability and free radical formation, and the latter is essential in the clearance of debris and bacteria, via phagocytosis, fibroblastic action, and the generation of chemoattractants and other immune cells, before triggering the proliferative phase.1

For chronic wounds, the proliferative phase is key, as it generates epithelialisation and therefore sets the conditions for healing. Again, macrophages, fibroblasts and their related cells play a key role in the matrix formation, angiogenesis and, eventually, wound contraction with visible remodelling and maturation.1

A comparative study was performed with 266 patients with acute wounds of different aetiologies, between Amicapsil (n=88), Gentaxan (antibiotic based powder, n=90) and Ioddicerin (antisepamicapsiltic-based powder, n=88). It demonstrated 60% improved wound healing times, with MPPT taking 3.0±0.9 days compared with 7.0±1.2 for Gentaxane and 8.0±1.1 for Ioddicerin.6 This study demonstrates noticeable improvement in wound healing using MPPT compared with antibiotic and antiseptic formulations. Similar findings were seen in a cohort of nine acute dehisced surgical wounds7 and an individual case study of a patient with SCI with a chronic wound.11 The literature also describes much shorter duration of treatment required for acute wounds (days) compared with chronic (months).6 7 11

Implications for military practice

Amicapsil has potential benefit for the patients of DMRC, especially those who have developed SCI-IDS and have chronic, non-healing wounds. These potential benefits include reducing the number and duration of wound-related admissions to DMRC, earlier commencement of effective rehabilitation, decreased pain and increased patient mobilisation. In complicated wounds requiring surgical input for secondary complications such as osteomyelitis, Amicapsil can be used to prepare for surgery by reducing any concurrent tissue infections.5 There is also a potential role for Amicapsil in the treatment of acute wounds to prevent progression into chronicity. Further experience is required with Amicapsil at DMRC to confirm these assumptions.