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Disclosure
There is a potential for bias in slides 40-44. This has been mitigated
by providing full references, referring to scientific names and
providing materials/methods and raw data for experimental results.
Disclosure of
Commercial Support
Mitigating Potential
Bias
Learning Objectives
1. Antibiotic Resistance and Wound Infection
2. Biofilms 101
1. Biofilms in chronic wounds
1
2
Antibiotic Resistance
In 2013 - 23 million antibiotic Rx were written in
Canada
o 45% respiratory, 16% upper respiratory, 14% UTI, 10% ear, 20% other
o Many of these infections may not have required antibiotic therapy (eg.
virus)
http//www.sciencephoto.commedia11428enlarge
http://phil.cdc.gov/phil/home.asp
Staphylococcus aureus
Enterococcus faecium
VRE
Enterobacter spp.
CRE
MRSA/VRSA
No ESKAPE
Pseudomonas aeruginosa
MDRPA
Klebsiella pneumoniae
CRE
Acinetobacter baumannii
MDRAB
Q. Where do antibiotics
come from?
Alexander Flemings Nobel Laureate Speech
A. Bacteria
http://microbewiki.kenyon.edu/index.php/Streptomyces
Bacteria in these caves have been isolated for an estimated 4 million years
They are on average resistant to 3-4 clinically used antibiotics
Glycopeptide Antibiotics
Front-line treatment for serious Gram-positive
infection (MRSA)
Two used clinically vancomycin and
teicoplanin
Three second-generation televancin (2009),
oritovancin, dalbavancin (2014)
All have the same primary mechanism of
action
Resistance exists for all
murF
ABh
ASt
ABh
Producers
VRE vanA
R
VRE vanB
R
VVE
H
APa
Clinical
Pathogens
P. apiarius PA-B2B
R
S. coelicolor
S
ASc
Environmental
Number of
Antimicrobial
NDA = 1
17
Considerations
Antibiotics and subsequent resistance are natural
phenomena
Microbes can adapt quickly
Antibiotics impact the healthy microbiome and
select for resistance in human pathogens
Alternate strategies are desperately needed
So Why am I here?
What does this have to do with wound care?
19
Contamination
Haemostasis
Colonization
Inflammation
Vigilance required
Critical
ColonizationRemodeling
Infection
Proliferation
Intervention required
20
Principles of best practice: Wound Infection in clinical practice. An International Consensus. London: MEP Ltd, 2008.
Available from www.mepltd.co.uk
21
Infection
Colonization
Critical Colonization
Harrison et al. 2008. Nature Rev Micro
Phillips et al. 2010. Wounds International
EPS:
an
electrostatically
charged
mix
of
eDNA,
polysaccharides, and protein
Structurally heterogeneous and fluid
(structure can change to form ridges,
layers, or microcolonies - depending on
environment and genetics)
Adherence to a surface (biotic or abiotic)
Biofilm Physiology
Aerobic
Neutral pH
Readily available
nutrients
High antimicrobial
penetration
A.
B.
C.
D.
Anaerobic,
Acidic pH
Scarce nutrients/by-products
Low antimicrobial penetration
In a multispecies biofilm
T=0
D1
T=0 D1
W1 W2 W3 W4
W2
Family Comamonadaceae
Curvibacter sp.
Family Comamonadaceae
Family Burkholderiales
Sphingomonas sp.
Family Rhodospirillaceae
Family Bradyrhizobiaceae
Family Caulobacteraceae
Peptoniphilus sp.
Finegoldia sp.
Streptococcus sp.
S. aureus
Paenibacillus sp.
Corynebacterium sp.
W3
29
Biofilms in Wounds
30
VS
Antibiotics
Antimicrobial Silver
Phoenicians
Water purification
1000 BCE
Hippocrates healing
and anti-disease
1980-now
32
Gram (-)
Ag+
Gram (+)
Ag+
Ag+
SH
OUT
IN
Oxidizing Agent
e-
Reduced
Oxidized
Oxidized
e-
Reduced
ee-
+ e Ag2+
Ag2+
+ e Ag+
+ e Ag0
Reduction
Potential (V)
+ 1.80
+ 1.98
+ 1.17
+ 0.80
+ 0.64
Ag2O
+ 0.34
AgCl
+ e Ag0 + Cl
+ 0.22
Reduction potential
(+) potential (V)
= need for electrons
oxidation
All silver species are
different
Reactivity
35
AgCl
O2
O2
O2
Ag2O
Ag
Ag
Ag7NO11
37
Silver in Dressing
(mg Ag/100 cm2)
Silver Release
(4h in SWF)
Silver Oxysalts
40
107
Metallic Silver,
Silver (I) Oxide
Ag1+, Ag0
160
28
Metallic Silver
Ag1+, Ag0
440
Silver Na H
Zr Phosphate
Ag1+
210
Silver Sulfate
Ag1+
120
18
Silver Chloride
Ag1+
12
28
Silver Type
38
Silver Availability
4 hr silver release into RO H2O
400
200
ppm Ag+/dressing
ppm Ag+/mg Ag(s)
500
400
300
200
100
0
24
48
72
Time (hrs)
40
30
20
10
0
600
10
8
2
LOD
1
200 M
200 M
10 M
10 M
20 M
10 M
10 M
1 M
40
4 hr exposure in saline
log cfu/gauze
AgCl
8
6
4
2
0
P.aeruginosa (blavim-2)
**** ****
****
****
*
****
10
log cfu/gauze
10
8
6
4
2
0
****
***
***
In Vitro In Vivo
Efficacy
Porcine Burn Biofilm Model
Log 10 value [cfu/mL]
10
5
LOD
0
W2
W1
W4
T=
D4
W
1
W2
W3
Curvibacter sp.
Comamonadaceae
family
Burkholderiales order
Sphingobium sp.
Caulobacteraceae
family
Peptoniphilus sp.
Helcococcus sp.
Finegoldia sp.
Anaerococcus sp.
S. aureus
Staphylococcus sp.
Macrococcus sp.
Paenibacillus sp.
43
W1
W3
W2
W4
D1
W1
W2
W3
W4
44
Additional Considerations
Infected wounds may require additional
interventions such as systemic antibiotics (oral or
intravenous), dressing selection to support
moisture balance and debridement of necrotic
tissue.
The wound management team, including the
patient, must have clearly identified endpoints
(goals or outcomes) with rationale for all
decisions related to wound care.
46
Summary
Systemic antibiotics might not be effective even in
the absence of a resistant microbe Antibiotic
stewardship is critical
Many if not all chronic wounds have a multi-species
biofilm established with intrinsic antibiotic resistant
The patient may have co-morbidities significantly
impacting healing
We still have a lot to learn about the influence of
microbes on healing pathways
The wound team is multi-disciplinary
Innovative treatment strategies start with you
47
http://www.woundsinternational.com/clinical-guidelines/wound-i
nfection-in-clinical-practice-an-international-consensus
http://www.woundsinternational.com/clinical-guidelines/intern
ational-consensus-appropriate-use-of-silver-dressings-in-woun
ds
https://www.scribd.com/doc/261794917/Clinical-Information48
Tool-a-Closer-Look-at-Silver
Thank-You
The Canadian Wound Care Community Collaborators
Michele Suitor
Dr. Andrew Myles
Jane Ratay
Dr. Raymond Turner
Marlene Varga
Dr. Mi Zhou
Westview Health Center Wound Clinic
Alberta Provincial Microbiology Lab
Questions and
Discussion
50
Supplementary
51
2000
1500
****
****
****
E.coli
1250
P.aeruginosa
S.aureus
850
500
80
**
60
40
50
40
*
*
E.coli
P.aeruginosa
S.aureus
30
20
20
10
*
*
450
1000
Clinical Performance
50 patients, mixed etiology wounds
o 25 men and 25 women
Spina, C.J., Lischuk, D.L, CE Mark Technical File: Scientific and Clinical Report. Exciton Technologies Inc.,
December 2011, In Support of European Regulatory Submission
53
Multi-Center Clinical
Evaluation
patients
entered (4 week) study with
chronic (non-healing) wounds
93% of patients perceived a reduction in pain
(with no pain reported upon dressing application)
Day 0
Conclusion:
Higher oxidation state silver (in Exsalt wound dressing)
is effective for chronic and critically colonized wounds.
Day 6
Day 16
Data on file - GMA Multi-Site
Study
54
Positive outcomes
Size in 16 out of 20 stalled chronic wounds
Decrease in cumulative pain scores
Patricia
Patricia Coutts, Grace
Grace Modelski,
Modelski, Laurie Goodman, Judy Ryan, R. Gary Sibbald
Sibbald M.D.
M.D.
** 20
20 out
out of
of 30
30 total
total patients
patients analyzed
analyzed to
to date
date
Positive outcomes
Reducing wound size: 52.3 cm2 to 34.1 cm2
Visual improvement in bacterial burden
Decrease in exudate
Symptom
# Improved
Pain
Oedema
Stalled Healing
Malodor
Bakeer
Bakeer M,
M, Vair
Vair A,
A, Keast
Keast D,
D, Evaluation
Evaluation of
of Silver-impregnated
Silver-impregnated Dressings
Dressings in
in a Clinical
Clinical Setting:
Setting: Observations
Observations on
on Efficacy
Efficacy and
and
Practicality,
Practicality, CAWC 2012
Microbial Ecology of
Wounds
INCLUSION AND EXCLUSION
CRITERIA
Inclusion
Exclusion
Systemic antibiotics in
previous 2 weeks
Day 1
V1 V2
V1
Swab
Week1
V3
Debridement
Week2
V4
Week3
V5
Dressing Change
Week4
V6
57
exsalt cut
to size,
foam
secondary
dressing
Note: Debridement samples have an inverse
correlation to streptococcus (assuming dead
slough). DNA analysis does not indicate
58
live/dead cells.
Infected Surgical
Wound
59
Right Flank
Non-Healing VLU
December 4, 2013: Started on
Aquacel Ag + Mepilex
December 12, 2013: NU-GEL
+ Alldress
December 19, 2013: Biopsy
taken, NU-GEL, calcium
alginate, Alldress
January, 2014: Mepilex Ag and
coban wrap
Week 2
Week 4
61
Day 2
Week 2 - Healed
Recurring Cellulitis
Day 0
Week 1
Wound measurements
improving
Week 2
Week 4
Increase of granulation
Continued improvement,
wound eventually closed
65
Fistula infection 1
month post surgery
Day 0
Week 4
66
Recurrent VLU
Week 1
Day 0
Week 2
Week 3
Week 4
67
Questions?
68