Case reports on the use of antimicrobial (silver impregnated) soft silicone foam dressing on infected diabetic foot ulcers

ABSTRACT

This article described four patients who had an episode of an infected foot ulcer, and subsequently treated with a novel antimicrobial soft silicone foam dressing together with standard off‐loading and antibiotic therapy. Qualitative description of the ulcer‐healing process was documented. All four ulcers showed positive wound contraction and reduction in size throughout the follow‐up period ranging from 3 to 16 weeks. In addition, clinical signs of infection were absent at the end of the follow‐up period. Moreover, surrounding skin maceration and trauma were absent in all wounds. Adequate moisture control was also achieved with the evidence of a healthy red granulating base, and a thin layer of clear light exudate in three out of the four cases. However, these reports had very little evidence to show the dressing's effectiveness in combating wound infection, but there might be some possible clinical efficacies of the dressing to control infection. Appropriate antibiotic therapy and off‐loading are still essential components when treating diabetic foot infection.

INTRODUCTION

In Asia, the number of people suffering from diabetes mellitus (DM) is more than double from 62 to 132 million between 2000 and 2010 (1). And, Singapore figures in 2004 showed that about 8·2% of adults between 18 and 69 years old were suffering from DM (2). The prevalence of DM in Singapore is amongst the highest in the Western Pacific region (3) (see Table 1) and it had been estimated that every day, two people lose a leg to diabetes (4).

Table 1.

Prevalence of diabetes mellitus in the Western Pacific region. (adapted from Cockram (4))

Country	Prevalence (%)	Year	Comment
Vietnam	1·4 *	1990	Hanoi
	2·5		Ho Chi Minh City
China	2·5	1994	Age 25–64
Indonesia	5·7	1992	Jakarta
Australia	5·0–6·0	Not reported	Caucasians Descent; Age standardised
Malaysia	> 8·0 *	1997	National Survey
Singapore	8·2	2004	National Survey; age 18—69
Hong Kong	8·9	1995	Age standardised
Taiwan	11·0	1995	Age standardised
Thailand	11·9	1995	North‐East Thailand (rural); age 30–74

^* Age adjusted figure.

People with DM are susceptible to the development of plantar foot ulcerations. It is believed widely that such incidences are attributed to a triad of factors, namely, the presence of sensory neuropathy, ischaemia, and an elevated plantar loading pressure (5). Foot ulcers and amputations are major causes of morbidity, disability as well as emotional and physical costs for people with DM.

Many non traumatic lower‐limb amputations and other costly medical treatment for chronic wounds were attributed to the incidence of diabetic foot ulcers. When the ulcers were infected, cellulitis and osteomyelitis could develop very quickly (6). Therefore, it is of paramount importance that any apparent local wound infection be treated early and aggressively. With the advent of silver impregnated wound dressings, combating local wound infection may be more efficient than before. This is because ionic silver released into the wound bed upon contact with wound exudates are toxic to multiple components of bacterial cell metabolism, thereby destroying their life cycle (7). Silver ions were also thought to be effective against biofilms (8), described as the layer of slime composed of polysaccharides, proteins, nucleic acids and microbial cells (9). Biofilms had been reported to be an integral component in causing local wound infection of chronic wounds (10).

These case reports described four patients who had an episode of an infected foot ulcer each, and subsequently treated with antimicrobial soft silicone foam dressing (Mepilex Silver, Molnlycke Gothenburg, Sweden). Mepilex Silver (Ag) is an absorbent polyurethane foam dressing impregnated with silver sulphate (AgSO₄) salts, combined with the benefits of Safetac (soft silicone) incorporated at the wound contact surface 11, 12.

Silver ions are released into the wound bed from the dressing upon contact with wound exudates, and the dressing has a rapid (within 30 minutes) and sustained antimicrobial activity (up to 7 days) against a wide range of diabetic foot wound pathogens (13). It had previously been reported to be effective in inhibiting growth of commonly found pathogens in the diabetic foot, including Methicillin Resistant Staphylococcus Aureus (MRSA), using the zone of inhibition (ZOI) method (14). The dressing had compared well with other silver dressings in terms of combating pathogens and improvements in healing rates (15). Safetac dressing (Mepitel, Molnlycke) had previously been shown to reduce overall costs by accelerating healing and reducing wound pain and resource use in patients with burn wounds (16). It had also prevented trauma to the wound by protecting the stratum corneum (17) and new epithelialisation tissue during dressing change (18).

A recent observational study had also reported that Mepilex Ag was effective in removing clinical signs of infection in most of the wounds treated (15). Prospective open studies of mixed aetiology infected wounds treated with Mepilex Ag had also shown good outcome in terms of cost‐effectiveness and wound size reduction 19, 20, 21. The combination of silver antimicrobial properties and Safetac soft silicone technology, in conjunction with antibiotics and off‐loading, might also be used to manage infected diabetic foot ulcers, and at the same time allow for atraumatic dressing removal.

The aim of these case reports was to evaluate the efficacy of antimicrobial soft silicone foam dressing (Mepilex Ag) in treating infected diabetic foot wounds non comparatively. The cases were randomly picked when they were referred for podiatry management of the foot wounds after surgical intervention if any. At the point of referral, all cases showed signs of both clinical and laboratory infection at the wound site. The standard podiatrist management of all four wounds included regular sharp debridement of surrounding callosities, non viable and slough tissues if any, and standard off‐loading with customised insoles. The clinical outcome of the ulcer‐healing process would be discussed qualitatively.

CASE 1 –POST AMPUTATION WOUND

Clinical history

A 63‐year‐old Malay man presented with a swollen left second toe ulcer on 3 July 2007 at the accident and emergency department. No prior treatment was administered as the patient immediately sought help at the emergency unit upon discovering the swollen toe. He had a history of type 2 diabetes, hypertension and hyperlipidaemia. The second toe was swollen with heavy exudate and presented with a foul smell. Dorsalis pedis pulse was still palpable but the posterior tibial pulse was poorly felt. Erosion of the distal and middle phalanges of the second toe with soft tissue lucencies was present on X‐ray. Osteomyelitis of the second toe was present.

Wound history

Subsequently, ray amputation of the toe was done on 4 July. Both tissue cultures at the amputation site and wound swab at the wound bed were taken on the same day. Staphylococcus Aureus, Pseudomonas Aeruginosa and Enterococcus Species were present. Intravenous clindamycin 300 mg 12 hourly was given daily for 3 days. Postoperative dressing used was hydrogel (Duoderm gel, ConvaTec Greensboro, NC, USA) and gauze impregnated with chlorhexidine.

Podiatrist's management

The wound was subsequently referred to the podiatrist for management on 30 July in preparation for outpatient care and off‐loading the foot. At the same time, he was undergoing gait training to build the left lower‐limb muscle in preparation for prosthetic fitting to the amputated right leg. The wound size was 3 · 2 cm × 1 · 1 cm, see Figure 1A. No laboratory evidence of wound infection was noted through a wound swab. The wound bed showed a rich red granulating base. However, there were purulent yellow discharges and the surrounding skin condition was still slightly inflamed and erythematous suggesting that the wound might still be critically colonised. Mepilex Ag was used in anticipation to reduce the chances of further wound infection on the surface, and the Safetac layer would allow new epithelialised cells to migrate across the wound margins, promoting a moist wound healing environment (11). He was subsequently discharged on 10 August, and the wound was managed as an outpatient with every other day dressing changes by the caregiver. The wound measured 3 · 0 cm × 1 · 0 cm, without clinical signs of infection present at the day of discharge, but the dressing regimen was not altered because the wound was still at risk of infection. The wound had hypergranulated on 11 September, and 75% silver nitrate was used to reduce the hypergranulating tissues with no change to the dressing used. A few weeks later on 28 September, the wound surface area had reduced dramatically to 1 · 0 cm × 0 · 5 cm with mild hypergranulation and serous discharge. When a probe was inserted to explore the depth of the wound bed gently, bone fragments were dislodged from the deep wound bed of 1 · 5 cm. However, the patient was afebrile, alert and not nauseas, and hence continued treatment as an outpatient. Oral amoxicillin/clavulanate 625 mg twice daily for 1 week was prescribed for the patient. At this juncture, silver impregnated calcium alginate dressing (Searsorb Ag, Coloplast) was used to pack the deep wound bed, whilst the wound surface was dressed with absorbent soft silicone dressing (Mepilex, Molnlycke) as a secondary dressing, see Figure 1C.

Figure 1.

(A) 30 Jul 2007 –3·2 cm × 1·1 cm (B) Absorption of excessive exudate exactly to wound size. (C) 28 Sep 2007 –1·0 cm × 0·5 cm. (D) 5 Nov 2007 –fully healed wound. (D).

Clinical outcome

The surrounding skin of the wound did not show any signs of trauma such as maceration or skin breakdown throughout all dressing changes with Mepilex Ag. In addition, the Mepilex Ag dressing was held in place during changes. Excess exudate was absorbed into the foam layer exactly to the wound size, showing no lateral wicking, see Figure 1B. The use of oral antibiotics and Seasorb Ag were also important in controlling the infection of the wound, especially when the wound bed tunnelled deeply on 28 September. Mepilex Ag seemed limited in dressing deep tunnelling wounds, and best suited for superficial and shallow cavity wounds. The wound was healed on 5 November, see Figure 1D.

CASE STUDY 2 –POST INCISION AND DRAINAGE WOUND

Clinical history

The 64‐year‐old lady of Indian descent had a purulent discharging ulcer with sinus tracking on her plantar left sole on 12 July 2007. Excoriation of the skin was noted with surrounding cellulitis. Tenderness and warmness were also present. She is a known type 2 diabetic for 10 years and suffered from end stage renal failure undergoing haemodialysis. On plain X‐ray, a destruction lesion in the calcaneum associated with marked soft tissue swelling was noted. Vascular calcifications were also noted around the ankle joint and the first intermetatarsal web space. Both intravenous ceftriaxone 2 g once daily and intravenous cloxacillin 2 g 6 hourly for 3 days were given immediately.

Wound history

Skin and subcutaneous tissue wound debridement was performed on 15 July. The resultant wound was dressed with chlorhexidine soaked roller gauze according to the hospital's orthopaedic department protocol. Tissue culture and wound swab results showed that Pseudomonas Aeruginosa and Stenotrophomonas Maltophilia were present. The antibiotic regime remained as intravenous ceftriaxone 2 g once daily and intravenous cloxacillin 2 g 6 hourly for the next 3 days.

Podiatrist's management

The podiatrist saw the wound on 2 August when orthopaedic referred to podiatry on that day for wound management and off‐loading. At this point, the patient was still on the same antibiotics regime. The wound measured 5 · 2cm × 2 · 5cm, and was still about 1 cm deep, see Figure 2A, B. The wound bed was evident with sloughy tissues and heavily exudating. Surrounding skin was atrophic and fragile, with the foot still oedematous. Residual slough was further debrided gently with a sharp blade. The chlorhexidine soaked roller gauze dressing used was then changed to Mepilex Ag in view of the impending infection from the bone tissue culture results taken on 1 August where Pseudomonas Aeruginosa and Stenotrophomonas Maltophilia were still present. In addition, the soft silicone layer would serve to protect the fragile skin and hence reduce and further trauma to the atrophic skin (22), see Figure 2C. Excessive exudate could also be absorbed into the foam layer effectively. The patient was then discharged on 15 August with the continued use of Mepilex Ag. Upon discharge, the wound size remained relatively unchanged although pockets of red granulating tissues began to dominate the wound surface, but mild yellowish exudate and slough covering about 10% of the wound surface were still present. Both oral ciprofloxacin 500 mg and co‐trimoxazole (sulfamethoxazole 400 mg + trimethoprim 80 mg) once daily for 3 weeks were given to the patient upon discharge.

Figure 2.

(A) 2 Aug 2007 –far view. (B) 2 Aug 2007 −5·2 cm × 2·5 cm. (C) 6 Aug 2007 −5·0 cm × 2·2 cm. (D) 20 Sep 2007 −3·0 cm × 1·2 cm.

Clinical outcome

On 20 September, the wound had reduced in size and depth, 3 · 0cm × 1 · 2cm, see Figure 2D. Wound margin showed healthy epithelialising skin with no maceration. The wound bed showed a healthy red granulating base with minimal clear exudate. The patient did not return for follow‐up appointment on 30 October because the wound had fully healed as inspected by the caregiver when a courtesy telephone call was made to ascertain the reason for missing the appointment. Aggressive and appropriate administration of both intravenous and oral antibiotics eradicated the infection from the wound appropriately.

CASE STUDY 3 –HALLUX AMPUTATION WOUND

Clinical history

The 61‐year‐old Malay patient had a chronic ulcer on the plantar first interphalangeal joint first presented at the emergency department since 10 February 2007. He had bone excision performed on 13 February, given intravenous ceftriaxone 2 g once daily and intravenous cloxacillin 2 g 6 hourly for 3 days, and was subsequently discharged on 20 February for every other day dressing changes with hydrogel (Duoderm gel, ConvaTec) and gauze by the community polyclinic nurse. Oral amoxicillin/clavulanate 625 mg twice daily for 4 days was given upon discharge. However, the wound remained unhealed despite subsequent outpatient visits to the orthopaedic department and five hospital admissions (6 March, 14 May, 1 July, 9 July, 26 August) due to recurrent foot infection from the ulcer. He is a known type 2 diabetic complicated with nephropathy, retinopathy and peripheral vascular disease. Unfortunately on 3 September, the wound turned gangrenous. He was immediately admitted and given intravenous ceftriaxone 2 g once daily and intravenous cloxacillin 2 g 6 hourly for 3 days.

Wound history

The toe was amputated on 6 September after failing to improve. Postoperative dressing used was gauze impregnated with chlorhexidine according to orthopaedic department protocol for postoperative wound. The wound was clean and no pus was evident after the amputation. Intravenous ceftriaxone 2 g once daily and intravenous cloxacillin 2 g 6 hourly was given postoperatively daily for 3 days, while a wound swab was taken to ascertain the bacteria flora. The patient developed MRSA on the wound when the results of the wound swab were confirmed. Intravenous vancomycin 1 g and intravenous ciprofloxacin 400 mg 12 hourly each had also been administered since 7 September for five days.

Podiatrist's management

The podiatrist saw the wound on 11 September, which measured 3 · 3cm × 2 · 2cm, see Figure 3A. A heavily exudative, pink granulation wound base was noted with the metatarsal head partially exposed. The central core was also burrowed deep to about 0 · 3 cm. Silver impregnated soft silicone foam dressing (Mepilex Ag) was used because of the MRSA on 6 September. Two days later, the exposed metatarsal head was overlaid with healthy granulating tissue, and the central core appeared more superficial. A wound swab taken on 12 September confirmed the eradication of MRSA on the wound. The patient was discharged on 14 September, and rifampicin 300 mg and ciprofloxacin 500 mg twice daily for 2 weeks each were also prescribed. The wound remained relatively unchanged from 11 September upon discharge. On 27 September, the wound showed signs of contraction at the margins coupled with a less exudative base, see Figure 3B. The wound size was subsequently reduced to 2 · 5cm × 1 · 5cm on 15 October, where the wound bed was largely covered with 90% healthy granulating tissues with mild serous exudate (see Figure 3C), and further reduced to 1·4 cm × 0·9 cm on 17 December.

Figure 3.

(A) 11 Sep 2007 –3·3 cm × 2·2 cm with heavy exudate. (B) 27 Sep 2007 –less exudative base. (C) 15 Oct 2007 –2·5 cm × 1·5 cm. (D) 9 Jan 2008 –fully healed wound.

Clinical outcome

It was clear that the dressing provided adequate moisture balance without macerating the wound margins. It also provided a conducive environment for laying of new granulation tissue. It was unclear if the dressing was able to maintain the local wound environment free from further MRSA infection since the patient was given appropriate antibiotics upon discharge as well. However, the wound remained infection free without the use of antibiotics from 27 September 2007 till 9 January 2008 when the wound was completely healed, see Figure 3D.

CASE STUDY 4 –CHRONIC DIABETIC ULCER

Clinical history

The 52‐year‐old patient with chronic renal failure and 8 years history of type 2 diabetes had a non healing chronic ulcer on the plantar aspect of the left first interphalangeal joint since December 2005. He was also suffering from chronic renal failure and hyperkalaemia.

Wound history

The ulcer had been managed by another hospital and hence the management history was unclear. He presented at the emergency department on 23 July 2007 for a wound infection with foul smell. During history taking, the patient had only mentioned that incision and drainage was done in December 2005 at another hospital. No off‐loading devices were found and the patient came in with a pair of open toed sandals without any accommodative padding. Hallux rigidus was noted and the ulcer probably failed to heal because of increased pressure transferred to the interphalangeal joint as a result. The ulcer showed granulation tissue with increased warmth around the skin, and no documentation on the wound size was found at the emergency department. Serous fluid and some purulent discharge were noted without any bleeding, but no slough was present. A wound culture showed that Proteus Vulgaris, Klebsiella Species and Staphylococcus Aureus were present. Intravenous cloxacillin 2 g 6 hourly for 7 days was administered.

Podiatrist's management

The ulcer was referred to the podiatrist for off‐loading and local wound care on 30 July, and it measured 2 · 4cm × 0 · 7cm, see Figure 4A. It showed a healthy pink granulating base with minimal serous discharge, but malodour characterised by a musty, fetid and putrid smell was still present. This highly signified that bacterial load especially gram‐negative anaerobes might still be present on the wound surface (23). A layer of biofilm characterised by a layer of slime composed of polysaccharides, proteins, nucleic acids and microbial cells (9), as well as pale yellow adherent slough were also noticeable. Hence, sharp debridement was performed followed by application of silver impregnated soft silicone foam dressing (Mepilex Ag, Molnlycke). The ulcer improved marginally on 1 August, showing pockets of rich red healthy granulating base whilst about 90% of the wound bed was still covered with the pale yellowish adherent slough and it measured 2 · 3cm × 0 · 6cm, see Figure 4B. The slough was removed with sharp debridement again that day. He was discharged on 1 August and given oral amoxicillin/clavulanate 625 mg twice daily for 2 weeks. About 3 weeks later on 22 August, the ulcer healed further, measuring 1 · 5cm × 0 · 4cm with the biofilm still noticeable, see Figure 4C. The patient was subsequently lost to follow up and remained non contactable.

Figure 4.

(A)30 Jul 2007 –2·4 cm × 0·7 cm. (B) 1 Aug 2007 –pockets of rich red granulating tissue. (C) 23 Aug 2007 –1·5 cm × 0·4 cm with evidence of biofilm.

Clinical outcome

Wound contraction for this patient occurred promisingly despite being a chronic ulcer for the past 18 months. Wound margins were not compromised and offensive odour was adequately controlled noticed by marked reduction of the musty and fetid smell during dressing change on 1 and 22 August. No signs of acute infection were noted during dressing change on those 2 days as well. It should be noted that the patient was still taking oral antibiotics between 1 August and 14 August. As such, it would not be conclusive if Mepilex Ag was effective in maintaining the local wound environment free from further infection.

SUMMARY OF CASES

The mean age of the patients was 60 years old, with a mean duration of Type 2 DM of 11 · 25 years. The wound size of the patients ranged from 2 · 4cm × 0 · 7cm to 5 · 2cm × 2 · 5cm at the start of the reports, as shown in 1, 4. The wound depth varied from superficial to 1 · 5 cm. Slough was present coupled with surrounding skin erythema and inflammation. All four ulcers showed positive wound contraction and reduction in size throughout the follow‐up period ranging from 3 to 16 weeks. One wound was completely healed at 14 weeks (see Figure 1D), and another at 16 weeks (see Figure 3D). In addition, clinical signs of infection were absent at the end of the follow‐up period. Moreover, surrounding skin maceration and trauma were absent in all wounds. Adequate moisture control was also achieved with the evidence of a healthy red granulating base, and a thin layer of clear light exudate.

DISCUSSION

Most wound healing studies that had investigated on the efficacy of Mepilex Ag were non comparative, had a small number of patients, and even a smaller inclusion of diabetic foot ulcers. A recent single‐centred open, non randomised, prospective study of 30 patients was conducted to evaluate the efficacy of Mepilex Ag on reducing the clinical signs of local wound infection and the progression towards wound healing, as well as patient acceptance of the dressing in a variety of wound types (15). The study showed that 90% of the wounds had clinical signs of infection completely eradicated, and a complete healing rate of 53% with 27% almost healed at the end of 4 weeks. However, there was only one diabetic foot ulcer being included in that study.

A smaller scale explorative study featured approximately 30% reduction in wound size of 18 patients at the end of a 4 week period with the use of Mepilex Ag (20). That study included a total of three diabetic foot ulcers. Another open, non comparative study evaluating the benefits of Mepilex Ag in treating chronic wounds had three diabetic foot ulcers included out of 24 patients. Approximately 50% wound size reduction was achieved with two wounds completely healed after 8 weeks (21). However, it was not reported if antibiotics had been administered in the two studies mentioned. For the management of surgical reconstruction of Charcot midfoot deformity, it was reported anecdotally that Mepilex Ag could be used to dress external fixator pin wounds easily, as it could absorb drainage, neutralise bacteria and the foam layer provided some compression (24).

Therefore, it could be observed that very little conclusive studies have been done to show the clinical efficacy of Mepilex Ag in the management of diabetic foot ulcers. The four case reports presented herein would not be conclusive due to a lack of inclusion and exclusion criteria for patients, as well as a very small sample size that lacked a definite study period. Moreover, both intravenous and oral antibiotics had been indicated in all four cases prior to the use of the test dressing. Therefore, the findings could not show that Mepilex Ag was beneficial in healing infected diabetic foot ulcers clinically, although all wounds remained infection free at the last follow‐up date. The appropriate use of antibiotics and good local wound care is still of paramount importance when treating infected diabetic foot ulcers.

However, these reports could augment the abovementioned non comparative studies to pave the way for Mepilex Ag be included in larger, randomised control studies with other similar dressings such as Biatain Ag (Coloplast), Polymem Ag (Ferris Manufacturing Corporation), Urgocell Ag (Urgo Laboratories) and Allevyn Ag (Smith and Nephew) for specific wound types such as diabetic foot ulcers (15).

Biatain Ag was reported previously to be superior over Biatain in treating diabetic foot ulcers over a 6 week period in a comparative study (25). Apart from this, there seemed to be no other comparative studies on the use of silver foam dressings in treating diabetic foot ulcers. Urgocell Ag had been evaluated in terms of wound area reduction, and reduction of critical colonisation clinically, but the wounds treated were all venous leg ulcers (26).

It might be very useful to evaluate comparatively the benefits of silver containing foam dressings clinically, so that the strengths and weaknesses of each dressing named above could be identified for better informed choices when clinicians prescribed the dressing to patients. Besides comparing wound healing characteristics such as healing rate, control of infection and effective moisture balance control, it might also be very useful to investigate the plantar pressure reduction properties of the above dressings as all of them had a foam layer to provide some degree of cushioning. Previously, there was only one in vitro study comparing the ‘pressure relieving’ characteristics of foam dressings, where Allevyn (Smith and Nephew) emerged as an all round pressure relieving dressing (27). Invariably, increased plantar foot pressure is an important factor in the aetiology of diabetic foot ulcers (28). Therefore, choosing foam dressing that had superior pressure reduction properties might help to facilitate wound healing effectively.

CONCLUSION

These case reports had very little conclusive evidence to show that Mepilex Ag is effective in treating infected diabetic foot ulcers. Since antibiotics regime commenced before the use of the dressing in all cases, and off‐loading was also indicated in case study 1, 2 and 4 at the same time when the dressing was first applied, it is unclear if Mepilex Ag attributed significantly to the outcome. However, these reports might augment previous small‐scale non comparative studies that Mepilex Ag be put forward for further larger scale comparative studies to test its efficacies in healing infected diabetic foot ulcers clinically. On the other hand, it should be noted that together with the use of appropriate antibiotics, it allowed infected ulcers to have a positive wound environment for contraction and healing to occur. Skin surrounding the wound did not show any signs of trauma such as maceration or skin breakdown. Moreover, dressing change was carried out with ease, and exudate was absorbed into the foam layer exactly to the wound size, showing no lateral wicking. Offensive wound odour was also adequately controlled. It is therefore recommended that a comparative study be conducted to evaluate not only traditional wound healing characteristics, but also the pressure reduction capabilities of silver foam dressings. It might also be worthwhile to evaluate the extent of bioburden in wounds through a small serial comparative trial between Mepilex Ag and standard Mepilex.