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The compatibility of INTRASITE™ Gel and ACTICOAT™: An In-Vivo and In-Vitroassessment

An In-Vivo and In-Vitro assessment of the compatibility of ACTICOAT™ andACTICOAT 7 with INTRASITE™ Gel dressings inthe management of chronic wounds

IntroductionACTICOAT and ACTICOAT 7 (with SILCRYSTTM Nanocrystals) are effectiveantimicrobial barrier dressings which are indicated for use on partial and fullthickness wounds such as pressure ulcers, venous ulcers, diabetic ulcers,burns, donor and recipient graft sites. In-Vitro data has demonstrated that the nanocrystalline coating of silver rapidly kills a broad spectrum ofbacteria in as little as 30 minutes.

ACTICOAT must be kept moist to be effective. When exposed to moisture it can maintain bactericidal activity for at least 3 days. With ACTICOAT 7bactericidal activity can be maintained for up to 7 days. This bactericidalactivity will help to prevent and reduce infection of wounds.

Keeping ACTICOAT and ACTICOAT 7 dressings moist, may require re-wetting of the dressing with sterile water. However, some clinicians are using INTRASITE Gel/Conformable together with ACTICOAT and ACTICOAT 7 in order to keep the dressings, and the wound moist for longer periods oftime.

Case studies have been undertaken to show the effectiveness of thiscombination in the treatment of chronic wounds. To support these two in-vitro tests have been carried out to investigate the compatibility of the twodressings.

Dr. Juan Carlos López GutierrezHospital Infantil La Paz- Cirugía PediátricaPº de la Castellana, 26128046 - Madrid, Spain

The use of ACTICOAT™ on a severe traumawound in a paediatric patient

This case study demonstrates the use of ACTICOAT in combination withreconstructive surgery and tissue replacement in a paediatric patient withsevere trauma.

The patient was a 3 and a half year old boy with a trauma wound as aresult of a traffic accident. Originally, the patient suffered an open femurfracture to the left leg with injury to the femoral artery, femoral vein andsciatic nerve.

After reconstruction of the sciatic nerve and blood vessels, the patientpresented with a blood clot of the femoral artery and tissue destruction ofthe muscles of the thigh, lower leg and the front of the foot (Figures 1, 2 & 3).

TreatmentACTICOAT was applied along with INTRASITE™ Conformable for 8 days toavoid desiccation and infection of the bone (Figures 4 & 5). IntegraTM wasapplied (Figure 6) and covered with ACTICOAT to prevent infection.

After 5 months of treatment (Figures 7 & 8), despite sciatic paralysis, thepatient could walk without assistance.

TMJohnson & Johnson

Figure 1

Figure 2

Figure 3 Figure 4 Figure 5

Figure 6 Figure 7 Figure 8

Marcus Guergen, Senior consultant surgeonHead of Outpatient Wound Clinic, Dept. of Surgery, Sørlandet Sykehus HF, Flekkefjord, Norway

The effect of ACTICOAT™ 7 and INTRASITE™ Gelon a mixed aetiology leg ulcer

BackgroundThe patient was a 67 year-old female with a small ulcer on the top of herright foot, which had been present for approximately 6 months.

On examination on 19th December 2001, the ulcer measured 2.0cm x1.5cm x 0.4cm, with slough present in the ulcer bed. The skin surroundingthe ulcer, measuring approximately 16cm x 10cm was reddened.Considerable pain was experienced by the patient. The cause of the ulcer was classified as a combination of arterial and venous disease,complicated by an allergic reaction around the ulcer.

TreatmentThe ulcer was first debrided under local anaesthetic. Followingdebridement the ulcer site was treated with INTRASITE™ Gel and ACTICOAT™ 7, whilst the allergic reaction was treated with hydrocortisone1% ointment. The dressing was removed, and the ulcer assessed once aweek.

The Outcome On examination of the ulcer on 19th January 2002, granulation tissue waspresent in the wound bed, and the ulcer had reduced in size to 1.0cm x0.8cm x 0.1cm (see fig. 2). The reddening of the skin surrounding the ulcerhad improved considerably, and the patient experienced less pain.

A further examination on the 25th February 2002 showed that the ulcerhad further reduced in size, and now measured 0.3cm x 0.3cm withgranulation tissue reaching the edges of the ulcer (see fig. 3). Thereddened skin surrounding the ulcer had shown further improvement, andthe patient no longer was experiencing any pain.

At this point, the treatment with ACTICOAT 7 was stopped, and localtherapy continued using hydrocolloid dressings. At a final examination on16th April 2002 the ulcer had healed completely with just a scar and signsof hyper-pigmentation present.

An ulcer which earlier had not shown any signs of progression, despitevarious treatment therapies, progressed well, and without complicationswhen ACTICOAT 7 (in conjunction with INTRASTE Gel) was used. Thistreatment regime provided a high degree of patient comfort.

Fig1 - The wound at commencement of treatment.

Figure 2 - The wound at 17th January 2002

Figure 3 - The wound at 25th February 2002

Fig 4 - The wound at 16th April 2002

Marcus Guergen, Senior consultant surgeonHead of Outpatient Wound Clinic, Dept. of Surgery, Sørlandet Sykehus HF, Flekkefjord, Norway

The use of ACTICOAT™ 7 and INTRASITE™ Gel ona patient’s trauma wound with venousinsufficiency

BackgroundThis case study is about an 81 year old lady who fell in her home in March2002 and suffered a large wound in the area medial to the kneecap. Shehad previously been a patient at the Outpatient Wound Clinic due to a largeulcer on her right leg. This had been treated with, among other things, skingrafting and treatment was completed on 5 March 2002. The patient wasknown to have venous insufficiency.

Wound evaluation The patient came to the Outpatient Wound Clinic on the 15 April 2002(Figure 1). Examination showed a large necrotic wound medial to the patellawith the dimensions 8.0 x 3.5 x 1.5 cm. The ulcer did not probe to bone.There were evident signs of infection. There was no doubt that the woundwas in the inflammation stage. The patient was admitted to the hospital.

TreatmentDebridement was performed surgically, and a 10-day course of systemicantibiotic therapy was started. This was done to prevent the infectionspreading into the joint.

ACTICOAT™ 7 moistened with sterile water was used in combination withINTRASITE™ Gel as local therapy. The wound was assessed every other daywhile the patient was in the hospital, just by lifting up the ACTICOAT 7dressing. This allowed us full control of the wound.

The patient was sent home after one week at the hospital on 22 April 2002(Figure 2). The wound was now granulating. The treatment continued at theOutpatient Wound Clinic where a new ACTICOAT 7 dressing was appliedonce a week. The patient reported the dressing as being very comfortableand allowed her to continue her daily activities as normal.

Examination on 27 May 2002 (Figure 3) showed an ulcer reduced from 8.0 x 3.5 x 1.5 cm to 4.0 x 2.2 cm. Granulation tissue was present on thewound bed and there were no signs of infection. The ulcer marginsshowedsigns of re-epithelialisation. Skin grafting proved to be unnecessary. Use ofACTICOAT 7 was stopped, and the ulcer was treated locally with ALLEVYN™.

ConclusionThis case study shows the successful use of ACTICOAT 7 on a patient withvenous insufficiency and an infected traumatic wound.

Figure 1 - The wound before commencement of treatment 15 April 2002

Figure 2 - The wound at 22 April 2002

Figure 3 - The wound at 27th May.

In-Vitro assessments of the compatibilty ofACTICOAT™ and INTRASITE™ Gel dressings

IntroductionTo support the use of ACTICOAT in conjunction with INTRASITE™ Gel, two in-vitro tests have been undertaken toinvestigate the compatibility of the two dressings:

Test 1: ACTICOAT bioactivity when used with INTRASITE Gel - to confirm INTRASITE Gel does not affect theactivity of ACTICOAT

Test 2: The rheological effect of INTRASITE Gel when used with ACTICOAT - to confirm ACTICOAT does notaffect the rheology of INTRASITE Gel

Test 1: ACTICOAT bioactivity when used with INTRASITE Gel

MethodTwo in-vitro antimicrobial activity tests were used to determine the ability of the dressing to kill a variety ofimportant clinical pathogens.

Bacterial Reduction Test (Log) – This test is performed to determine the ability of the dressings to kill a wide varietyof important clinical pathogens. Inocula of bacteria, suspended in tryptic soy broth, were applied directly to thesurface of the dressings. After 30 minutes and 2 hours the bacterial reduction of viable organisms remaining oneach of the dressing was compared. The microorganisms used in this experiment were: S. aureus and P.aeruginosa, (two antibiotic resistant strains of these organisms).

Corrected zone of inhibition - Specimens of each of the dressings were placed onto a lawn of bacteria (P.aeruginosa) and the zone of no growth surrounding the dressing was determined over a 24 hour incubation periodthen the specimen was transferred to a fresh lawn of bacteria. This is repeated every 24 hours for a 7 day periodand the zone of no growth determined after each incubation.

2.54cm x 2.54 cm pieces of ACTICOAT dressing were coated with 0.7 g of INTRASITE Gel. For comparativepurposes, the coated ACTICOAT dressing without wound gel was also tested. ACTICOAT dressing pieces wereinoculated with 0.2 ml of a bacterial suspension. An untreated ACTICOAT dressing served as the control. The restof the test was conducted as per the procedure except that S. aureus samples were eluted in STS with increasedNaCl to facilitate elution of the organisms.

ResultsResults from the CZOI tests are shown in Table 1.The results from the Log Reduction Tests are shown in Table 2

Table 1: CZOI of ACTICOAT dressing coated with INTRASITE Gel

Table 2: Log reduction in bacterial load by ACTICOAT dressing coated with INTRASITE Gel

NT = Not tested

Sample

INTRASITE Gel treated dressing

CZOI (mm) vs P. aeruginosa

Test

7

ACTICOAT control

6

CZOI (mm) vs S. aureus

Test

7

ACTICOAT control

6

Hydrogel

Untreated ACTICOAT

INTRASITE Gel treated dressing

Log reduction in Ps.aeruginosa

30min incubation

5.6

2 hr incubation

NT

5.3 NT

Log reduction in S. aureus

30min incubation

4.9

2 hr incubation

4.3

3.0 4.3

In-Vitro assessments of the compatibilty ofACTICOAT™ and INTRASITE™ Gel dressings cont...

ACTICOAT with INTRASITE Gel gave zone sizes similar to the ACTICOAT dressing used alone. Reduction inbacterial count for treated and untreated ACTICOAT dressings are tabulated in Table 2. When P. aeruginosa wasused as the inoculum, both plain and treated ACTICOAT dressings reduced the microbial load to a non-detectablelevels within 30 minutes. For S. aureus, the gel treated ACTICOAT did display reduced kill rates relative to theregular ACTICOAT dressing. At the 30 minute time point the dressing with INTRASITE Gel still displayed a threelog reduction in bacteria, but displayed the same level of kill at 2 hours.

A log reduction of 3 or greater is considerable with regard to antimicrobial efficacy. Assuming that 10,000,000bacteria were present at the outset (equating to 107) a 3 log reduction would equate to a reduction to 10,000 CFU(Colony Forming Units). If the log reduction was greater than 4 this would equate to less than 1000 CFU remainingand a log reduction of greater than 5 would equates to less than 100 CFU present after the test period. After 2hours, the log reduction was 4.3 for S.aureus which would equate to less than 1000 CFU present. With P.aeruginosa, the antimicrobial was faster acting. The log reduction of 5.3 would equate to less than 100 CFU after30 minutes.

DiscussionNo significant impact on zones of inhibition was detected with treating ACTICOAT with INTRASITE Gel. This studyshowed that the ACTICOAT continued to give a considerable reduction in bacteria at both time points. The resultsgive confidence that the two dressings can be used in combination without comprising the antimicrobial efficacyof ACTICOAT.

In-Vitro assessments of the compatibilty ofACTICOAT™ and INTRASITE™ Gel dressings cont...

Test 2: The rheological effect of INTRASITE Gel when used with ACTICOAT

MethodEight samples of ACTICOAT dressing were coated with INTRASITE Gel. INTRASITE Gel was applied at 2mm/cm2

(equivalent to 20g over a 10x10cm dressing).

Samples were aged at 32oC for up to seven days sealed in light / moisture impregnable foil pouches. After 0, 1, 2and 7 days, duplicate samples were removed from storage.

Samples coated with INTRASITE Gel were scraped and the gel rheology determined. The standard specificationoscillation and flow tests were performed in attempts to determine whether the INTRASITE GEL was being adverselyaffected by anything that the ACTICOAT was excreting or absorbing. In addition, a creep test was performed,measuring the displacement that the sample made under a suitable low load. Also, a more complex oscillationtest was used to try and determine the limit of elasticity when oscillated at “zero” frequency.

All tests were performed on TA AR 500 Rheometer with temperature 25oC / Parallel plate with a 2mm (2000um)gap.

ResultsThe INTRASITE Gel that was removed from ACTICOAT dressings during the test did become discoloured as itabsorbed silver, however this discolouration diminished over time taking on a brownish yellow colour after 7 days.the subjective texture and appearance of the INTRASITE Gel after removal from the acticoat dressings did not feeldifferent from between the fingers of the operator.

The rheological data showed that over the course of the test, the INTRASITE Gel did show a slight increase inviscosity and elasticity (see fig 1), but this was not evident subjectively.

Figure 1

Figure 1 Elasticity of Intrasite gel after contact with Acticoat dressings for up to 7 days. Elasticity (G’) andDynamic Viscosity (n’) @ 5Hz/50 Pa

DiscussionThere is little noticeable rheological effect on the INTRASITE Gel from being in contact with ACTICOAT for a one day,two day, or seven day period. Over the 7 day period of this experiment, the INTRASITE Gel is subjectively the same to the touch, although rheological data shows it to be slightly thicker and stiffer. The results of this test suggest that ACTICOAT and INTRASITE Gel are compatible for use together.

In-Vitro assessments of the compatibilty ofACTICOAT™ and INTRASITE™ Gel dressings cont.

ConclusionsClinicians do use ACTICOAT and ACTICOAT 7 in conjunction with INTRASITE Gel in the treatment of chronicwounds, and this is supported by both in-vitro and in-vivo data. The in-vitro tests suggest that althoughdiscolouration of the gel is observed, the bioactivity is not compromised. The case study results provide in-vivoevidence that when used together, ACTICOAT and ACTICOAT 7 with INTRASITE Gel can provide an effectivetreatment regime for chronic wounds that may be susceptible to infection.

Notes

Notes

Wound ManagementSmith& Nephew Medical Ltd101 Hessle RoadHull HU3 2NBEngland

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