Title: SILVER DRESSINGS DOES THEIR EFFECT ON MICROBES JUSTIFY THE EXPLOSION IN THEIR USE
1SILVER DRESSINGSDOES THEIR EFFECT ON MICROBES
JUSTIFY THE EXPLOSION IN THEIR USE?
- OCTOBER 2005 ADELAIDE
- ASSOCIATE PROFESSOR
- MICHAEL WOODWARD
- AUSTIN HEALTH
2HISTORY OF SILVER
- Precious heavy metals have attracted health
interest through the ages - Silver coins used to purify water in middle ages
- Silver in many salves and ointments
- Silver nitrate recognised as antiseptic in 19th
century - SSDC first used in 1968
- Allowed more extensive use than silver nitrate
- Less skin discolouration
- Revolutionised burns management
3WEAKNESSES OF SSDC
- Ag rapidly binds to tissue Cl- , creating AgCl
,which is inactive
- So need to apply large quantities,and frequently
- Pseudo-eschar formed
- Binds tightly to wound surface
- Removal necessary but painful
- Can macerate wound
4NEW SILVER PRODUCTS
- Prolong the release of ionic silver
- Or absorb wound fluid into silver-impregnated
product - Utilize modern wound management principles
- Most based on existing modern products,with
silver added
5SILVER DRESSINGS AVAILABLE IN AUSTRALIA
6HOW DOES SILVER ENHANCE WOUND HEALING?
- Controls microbial burden
- Other effects
- Controls inflammation
- Alters proteases
- Promotes apoptosis
7EFFECTS OF MICROBES ON WOUND HEALING
- 1. Contaminate all wounds
- 2. Critical colonisation
- Delays healing
- May lead to
- 3. Infection
8MICROBES WOUND HEALING
- Contamination may be helpful to wound healing
- Promotes beneficial inflammation
- Increases blood flow
- Critical clonisation/infection delays healing
- Bacterial endotoxins elevate cytokines (eg IL-1
and TNF),causing increased proteases and reduced
growth factors - Vessels occluded
- Bacteria spread to and damage adjacent healthy
tissue
9BIOFILMS
- Microbes on wound surfaces usually form a biofilm
- Complex community embedded in a polysaccharide
matrix - Resembles a single organism
- Excretes via channels,attracts and shares
nutrients,resists external threats - Bacteria within can reduce metabolism
(hibernate)
10BIOFILMS
- Bacteria in a biofilm up to 1000 times more
resistant to antibiotics - Protected by the matrix
- Reduced metabolism
- So factors which aim to control bacterial burden
must work on biofilms
11CONTROLLING MICROBIAL BURDEN
- ANTIBIOTICS
- May be effective for infection
- But increasing resistance
- In critical colonisation, often ineffective
- Biofilm resistance
- Multiple organisms
- Too late
- In surgery, giving Ab after operation increases
infection rate
12CONTROLLING MICROBIAL BURDEN
- ANTISEPTICS
- Much less resistance
- as short acting and locally acting
- Penetrate and control biofilms
- COMMONLY USED ONES
- Chlorhexidine
- Alcohol
- Iodine
- Silver
13EFFECTS OF SILVER ON MICROBES
- Attracted to the proteoglycans in cell walls
- mammalian cells lack these
- Denatures microbial proteins
- esp. those involved in respiration
- Also affects microbial DNA
14RESISTANCE TO SILVER
- Extremely rare
- One mechanism microbes develop ability to pump
silver out - Not seen in bacteria resistant to multiple
antibiotics - Not shown to spread between patients
15EVIDENCE FOR EFFICACY OF SILVER PRODUCTS
- 1. In Vitro
- 2. Animal Models
- 3. Human Studies
16IN VITRO STUDIES
- Bowler et al
- Foetal calf serum
- Inoculated with various organisms
- - At 0,4 and 9 days
- Small piece of Aquacel Ag or control hydrofiber
added - Cultured for persistent organisms
Bowler PG et al.J Burn Care Rehab 2004,25192-60
17BOWLER ET AL - RESULTS
- Single piece of Aquacel Ag nearly completely
eliminated microbes up to 9 days later - Despite reinoculations
- Effective against
- Pseudomonas
- MRSA
- VRE
- anaerobes
- fungi/yeasts
18IN VITRO STUDIES
- Wright et al
- Inoculated organisms onto dressings coated with 3
different silver forms - Nanocrystalline
- SSDC
- Silver nitrate
- then extracted surviving organisms 30 minutes
later - Results
- Nanocrystalline silver most effective
- SSDC partly effective
Wright BJ et al.Am J Infect Control 199826572-7
19IN VITRO STUDIES
20IN VITRO COMPARATIVE STUDIES
- Recent study compared antimicrobial effect of 4
products - Acticoat most rapid
- Contreet slower but effective against same broad
range of bacteria - Actisorb only effective within product(not at
wound surface) - Avance not effective
Thomas et al J Wound Care 200312101-7
21ANIMAL STUDIES
- Porcine contaminated wound model
- wounds created in young pigs
- contaminated with Ab-resistant bacteria
- then dressed
- then cultured and biopsied
Wright et al. Wound Repair Regeneration
200210141-9
22PORCINE MODEL - RESULTS
- Nanocrystalline silver dressing improved healing
- Better quality granulation tissue on inspection
- Better graft uptake
- 6/6
- compared to 0/6 control wounds
- Reduced metalloproteinases on Bx in
silver-treated wounds - Increased apoptosis after silver Rx
- healthy cell death
- the other, necrosis, causes inflammation and
tissue damage
23HUMAN STUDIES
- No gold standard study with silver
- Nearest is probably CONTOP
- Naturalistic comparator trial
- Partly randomised
- Silver or standard care which could be silver
- 1,000 patients to be enrolled
- Findings on first 352 presented at WUWHS meeting,
Paris July 2004
24CONTOP
25CONTOP
26P0.006
27CONTOP
28CONTOP
- Results on 619 patients at Silver Symposium in
Perth, September 2005 - 50 reduction in size at week 4 with Contreet
- 34 with standard care
29INTERPRETING CONTOP
- Not published
- Not fully randomised
- No rater blinding
- Outcomes clunky
- P values hard to understand
- Results apply only to this silver product
- and presumably sponsored by manufacturer
- but most drug research is
30CONTREET FOAM vs ALLEVYN
- 109 patients with chronic venous leg ulcer or
mixed arterial/venous ulcer - 13 Centres
- Healing stalled
- Less than 30 reduction in size at 4 weeks
- Features of critical colonisation
- Pain, appearance
31CONTREET FOAM vs ALLEVYN
- RESULTS
- CONTREET
- 45 reduction in size by 4 weeks
- ALLEVYN
- 25 reduction in size by 4 weeks
- OTHER SECONDARY ENDPOINTS IMPROVED WITH CONTREET
- less exudate
- less leakage
32RDNS/SILVER CIRCLE STUDY
- Planned 360 patients with wounds not decreasing
in size or signs of critical colonisation - Randomise to cadexomer iodine or silver product
(Iodosorb or Acticoat) - Follow-up 3 months 2-weekly reviews
- Endpoints wound size, use of antibiotics,
- adherence, wound swabs,
- nurse and client satisfaction
- Results 2007
33CHRONIC VENOUS ULCERS
- 25 patients with chronic venous ulcers
- Contreet foam use led to 56 reduction in ulcer
area over 4 weeks - IMPORTANT-not selected for colonization
- No comparator group
Karlsmark et al J Wound Care 200312351-4
34CHRONIC WOUNDS
- Randomised non-blinded study in chronic wounds
with no clinical infection, using an activated
charcoal silver dressing - Reduced bacterial levels in 85.1 of 67
silver-treated wounds by day 15 - Compared with 62.1 of 58 control wounds
- Healing times not reported
Soriano et al J Wound Care 200413421-3
35SIGNIFICANCE OF THESE LAST 2 STUDIES
- These suggest a role for silver even when
microbial burden not an obvious factor - Not clear if this influenced dressing selection
in CONTOP - probably did
- However, role of silver may still be via control
of microbes, as last study suggests
36BURNS STUDIES
- 1. Open-label non-comparator study with Urgotul
SSD - Low rate of Staph aureus colonisation
- 1 of 41 subjects
- 2. Another non-comparative trial with Aquacel-Ag
- 17 patients
- healed in average 14 days
- only one required grafting
1.Carsin et al J Wound Care 200413145-8 2.Caruso
et al J Burn Care Rehab 20042589-97
37DIABETIC FOOT ULCERS
- Non-randomised trial of diabetic foot ulcers
treated with Contreet in 27 patients - small comparator group of 6 ulcers in same
patients not treated with Contreet - average healing 56 over 4 weeks
- not reported in comparators
- two treated ulcers infected,compared to all 6
comparators
Rayman RG et al British J Nursing 200514109-14
38IS THIS EVIDENCE SUFFICIENT?
- By comparison to other areas of health practice
- POSSIBLY
- By comparison to pharmaceutical research
- DEFINITELY NOT
39COST EFFECTIVENESS DATA
- ALWAYS SEEMS TO JUSTIFY EXPENSIVE PRODUCT USE
- Use a commonsense approach
- And ask - can service or patient afford it,
even if cost effectiveness claimed
40HOW SHOULD THIS EVIDENCE INFLUENCE CLINICAL
PRACTICE?
- Consider silver dressings for critically
colonised wounds - and return to standard dressing once microbial
burden controlled - Try a different silver product if initial one
fails - But no human head-to-head trials and such trials
notoriously unhelpful - always seem to favour sponsors product !
41EVIDENCE-BASED USE OF SILVER
- Consider silver product in non-healing and slowly
healing wounds - even if no evidence of microbial critical
colonisation/infection - could biopsy first to establish such burden, but
evidence only exists for value of high counts
revealing infection, not lower counts and
colonisation - and silver may be effective even with no
microbial burden
42EVIDENCE-BASED USE OF SILVER
- Infected wounds need
- Antibiotic
- Debridement
- Silver may add extra benefit
- But no human studies
- Only support from in-vitro and porcine studies
43EVIDENCE-BASED USE OF SILVER
- Always return to first principles
- Fully and repeatedly assess
- Compress if venous
- Ensure adequate blood supply
- Reduce pressure
- Improve nutrition
- Treat co-morbidities
- Assess social circumstances
- Silver is not a panacea
44THE FUTURE
- A Challenge
- Design and participate in well-designed and
powerful trials - Avoid the temptation of easy research only
- More case series
- No comparator group
- Until then, use silver mainly for control of
microbial burden - This is where the evidence is currently strongest