An Integrated Treatment Pathway for Treating Diabetic Foot …BSN+for+webinar2.pdf ·...
Transcript of An Integrated Treatment Pathway for Treating Diabetic Foot …BSN+for+webinar2.pdf ·...
Use of DACC Technologyand Total Contact Casting
An IntegratedTreatment Pathway for Treating
Diabetic Foot Ulcers and Implications of Silver Resistance
Supported by an educational grant from BSN Medical
Faculty
Phillip J. Finley, PhD
Senior Research Scientist
Mercy Hospital
Division of Trauma and Burn Research
Springfield, Missouri
James McGuire, DPM, PT, CPed, FAPWHc
Director, Leonard Abrams Center for Advanced Wound Healing
Temple University
Philadelphia, Pennsylvania
Faculty Disclosures
Dr. Finley: Consultant – BSN Medical
Dr. McGuire: Grant/Research Support – BSN Medical, NuTech, Podimetrics, TEI BioSciences; Consultant – BSN Medical, Devon Medical Products, Zeomedix,; Scientific Advisor – Pedorthic Footcare Association; Promotional Speakers’ Bureau – 3M, BSN Medical, Hollister, Medline, Smith & Nephew, Steadmed, TEI BioSciences; Stock Shareholder – Creative Footwear Technologies
• This continuing medical education activity includes device brand names for participant clarity purposes only, due to the presence of different branded versions of the same device. No product promotion or recommendation should be inferred.
Learning Objectives
• After completing this activity, participants should be able to
– Explore the value of hydrophobic dressings in reducing bacterial colonization
– Assess the prevalence and implications of silver resistance
– Review the current literature supporting off-loading of diabetic foot ulcers to improve healing rates and the role of total contact casting as an evidence-based standard
– Review case studies on the use of hydrophobic bacteria-binding dressings and total contact casting for the treatment of diabetic foot ulcers
Hydrophobic Bacteria-Binding Dressings and Total Contact Casting: Review of Current Literature and Case
Studies
James McGuire, DPM, PT, CPed, FAPWHc
National Diabetes Statistics Report 2014
Centers for Disease Control and Prevention. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed March 7, 2015.
Total29.1 million diabetics in the United States –9.3% of the population
Diagnosed 21 million people (all ages)
Undiagnosed 8.1 million people (all ages)
Prediabetes 86 million people (20 years old and above)
New Cases1.7 million new cases of diabetes were diagnosed in people 20 years and olderin 2012
Estimated Diabetes Costs in the United States, 2012
• Total medical costs (direct and indirect): $245 billion
– Direct costs: $176 billion
• Average medical expenditures for people with diagnosed diabetes were 2.3 times higher than for people without diabetes
– Indirect costs: $69 billion
Centers for Disease Control and Prevention. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed March 7, 2015.
Diabetes
• 85% of all lower limb amputations in diabetics are preceded by a foot ulcer
• Diabetics who develop a foot ulcer have a 55x greater risk of infection
• If a DFU is open 30 days or longer it has a 4x greater risk of infection
DFU = diabetic foot ulcer.Singh N, et al. JAMA. 2005;293(2):217-228. The Diabetic Foot. St Louis, MO: Mosby; 2001:13-32. Yates C, et al. Diabetes Care. 2009;32(10):1907-1909. Lavery LA, et al. Diabetes Care. 2006;29(6):1288-1293.
Etiology ofNeuropathic Diabetic Foot Ulcers
Neuropathy Deformity
Repetitive Stress
Footwear
LifestyleCompliance
ActivityCompliance
VascularDisease
Pecoraro RE, et al. Diabetes Care. 1990;13(5):513-521. McGuire J. Adv Skin Wound Care. 2010;23(4):175-188.
Diabetic Foot Offloading:Goals of Treatment
American Diabetes Association. Diabetes Care. 1999;22(8):1354-1360.
Stabile Ambulationwith Aides
Assure Compliance
Prevent Reinjury
ReduceCostsRapid
WoundClosure
Low Plantar Pressure
Transitional Approach to Offloading
OpenWound
• TCC/iTCC• Wound isolation TCC• Football dressing
Shallow Wound or
NewlyClosed
• RCWs• Carville healing sandal• Felted foam
NewlyHealedWound
• OrthoWedge Shoe®
• Diabetic healing shoe
ClosedWound x 2-4
Weeks
• Depth shoe with rocker sole
TCC = total contact casting; iTCC = instant total contact cast; RCWs = removable cast walkers.McGuire J. Adv Skin Wound Care. 2010;23(4):175-188.
What is a TCC?
“A snug fitting below the knee cast that protects
insensitive limbs from repetitive trauma, promotes ulcer
healing, and allows patients to ambulate”
— Dr. Paul BrandFather of the TCC
Diabetes Mellitus. Garden City, NY: Medical Examination Publishing; 1983.
TCC Systems Are Designed to Address Barriers to Utilizing the TCC as a “Gold Standard”
• Easy to use – no learning curve
• Shortened application time
• Not messy
• Lighter
• Cooler
• Increased patient acceptance
• Functionality of traditional TCC
Results of 9 TCC Studies
• Average healing time:43.73 days
• Percent healed:88.9%Helm 1984; Sinacore 1987; Walker 1987; Mueller 1989; Meyerson 1992; Birke 1992; Lavery 1997; Armstrong 2001; Birke 2002
Fife CE, et al. Wound Repair Regen. 2010;18(2):154-158.
Healing/Days to HealTCC vs iTCC vs RCW
Armstrong DG, Lavery LA, Wu S, Boulton AJ. Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial. Diabetes Care. 2005;28(3):551-554. Fife CE, et al. Wound Repair Regen. 2010;18(2):154-158.
Healing Rate
Days to Heal
100
80
60
40
20
0
He
ali
ng
/Da
ys t
o H
ea
l
TCC RCWiTCC
90
70
50
30
10
51.9
82.689.5
58
41.6
33
Indications for TCC
• Plantar ulceration Wagner grades I and II
– UTHSC grade A0, 1, 2, or 3
• Neuropathic, pressure, traumatic
– Avoid: arterial, venous
• Neuropathic fracture (Charcot)
• Post-reconstructive surgery
McGuire J. Adv Skin Wound Care. 2010;23(4):175-188.
Contraindications for TCC
• Acute infection
• Fever
• Palpable lymph nodes
• Deep sinus tract or narrow deep wound
• Perfuse drainage
• Active dermatitis
• Excessive/fluctuating edema
• Claustrophobia
• Known noncompliance
• Arterial insufficiency Ankle-Brachial Index <0.8
• Wagner Grades 3, 4, 5
McGuire J. Adv Skin Wound Care. 2010;23(4):175-188.
Don’t Let ’em Take It Off!
• A higher proportion of patients with ulcers that were healed at 12 weeks in the iTCC group thanin the RCW group (82.6% vs 51.9%; P=.02).
• Of the patients with ulcers that healed, those treated with an iTCC healed significantly sooner (18.7 vs 15.2 days; P=.02).
Armstrong DG, et al. Diabetes Care. 2005;28(3):551-554.
TCC Complications
• A major area of concern is the risk of iatrogenic complications
• Complication rates range from 11%-30% of high-risk patients
• The vast majority of these complications are minor
• Wukich found that 93% of the complications are minor skin irritations and do not require a change in the treatment protocol
• The most important factor for decreasing the risk of iatrogenic complications is frequent cast changing
• The real fear is not producing a new ulceration but an infection that may develop at the site that would be attributed to the clinician!
Laing PW, et al. J Bone Joint Surg Br. 1992;74(1):133-136. Baker RE. J Am Podiatr Med Assoc. 1995;85(3):172-176. Myerson M, et al. J Bone Joint Surg Am. 1992;74(2):261-269. Sinacore DR, et al. Phys Ther. 1987;67(10):1543-1549. Wukich DK, et al. Foot Ankle Int. 2004;25(8):556-560. Guyton GP. Foot Ankle Int. 2005;26(11):903-907.
What Is“Good” Diabetic Foot Wound Care?
• Debridement of nonviable tissue
• Maintain moist wound healing
• Bacterial management
• Reduce excess inflammation
• Exudate management
• Edema management
• Maximize limb perfusion
• Metabolic control and nutrition
• Biomechanical offloading
Advanced Dressings Designed to Address Bacterial Burden
• Silver (all dressing categories come with silver option!)
• Cadexomer iodine
• Pigmented foam
• PHMB
• Honey
• DACC
PHMB = polyhexamine biguanide; DACC = dialkylcarbamoyl chloride.
The Spectrum of Wound Bioburden
Sterile Infected
Contaminated Colonized CriticallyColonized
Critical Point for Bioload Management?
Sibbald RG, et al. Adv Skin Wound Care. 2006;19(8):447-461.
Traditional Approach to Infection
• Systemic antibiotics
– Systemic adverse effects, tissue damage, allergic reactions
– Unable to reach tissues with reduced perfusion
– Limited effect on biofilm colonies
– Limited to specific “sensitive” bacteria
– Produce antigenic, inflammatory cellular debris
– Induce antibiotic resistance (methicillin-resistant S aureus, vancomycin-resistant enterococci)
– Topical hypersensitivity reactions
European Wound Management Association. http://ewma.org/fileadmin/user_upload/EWMA/pdf/Position_Documents/2006/English_pos_doc_2006.pdf. Accessed March 8, 2015.
Traditional Agentsto Control Bioburden
• Debridement: surgical, mechanical, autolytic, enzymatic
• Wound cleansing: macro- or microlavage
• Topical antiseptics: silver, copper, PHMB, iodine, methylene blue, gentian violet, cadexomer iodine, hypochlorous acid, hydrogen peroxide, Dakin’s solution, povidone-iodine, honey
• Topical antibiotics: mupirocin, gentamycin, bacitracin
• NPWT
• Superabsorbent dressings: hydroconductive, hydroretentive
NPWT = negative pressure wound therapy.
Negative Aspects ofAntiseptic Dressings
• High toxicity
– Example: High levels of silver, povodine-iodine, and Dakin’s solution were demonstrated to have a negative effect on fibroblast and epithelial cell proliferation
• Allergy to the agent
• Risk of bacterial resistance, cytotoxicity, inflammation, or discoloration
• Killing of bacteria will result in the release ofintracellular contents and endotoxins from destroyedcells into the wound
Lee AR, et al. Arch Pharm Res. 2003;26(10):855-860. Poon VK, et al. Burns. 2004;30(2):140-147.
Combating Biofilms
• Physical removal of bacteria from the wound prevents aggregation of bacteria into microcolonies, thereby preventing them from producing the necessary “minimal threshold concentration” needed to begin biofilm formation
– Debridement
– Antibiofilm agents
– DACC
– Antiseptic/antibiotic cleansers or dressings
– NPWT/superabsorbent dressings
Miller MB, et al. Annu Rev Microbiol. 2001;55:165-199.
Hydrophobicity of Microbes
• Wound pathogenic bacteria andfungi express cell surfacehydrophobicity because of certainhydrophobic structures on their cellsurfaces
– For cell-to-cell commmunication(eg, DNA exchange)
– To bind to molecules for nutrition
– To bind to surfaces to rest
– For protection against phagocytosis
– To adhere to host tissue (eg, in theinitial phase of wound infection)
Ljungh A, et al. J Wound Care. 2006;15(4):175-180.
Hydrophobic interaction is essential for microbial life!
Physical Binding of Bacteria and Fungi to DACC-Coated Fibers
Magnification x 2000 Magnification x 15,000
S aureus (yellow), P aeruginosa (purple),
Enterococcus faecalis (blue), Klebsiella species (green), Candida albicans (orange)
DACC Hydrophobic Technology
Cutting K, et al. J Wound Care. 2011;20(5):1-19.
DACC Technology
• Dialkylcarbamoyl chloride coating
• “Hydrophobic” molecular structure
• Irreversible binding of bacteria with hydrophobic molecules on its cell walls to the DACC-coated dressing material
• Once bound, the bacteria “inactivate” or exhibit a decreased rate of replication
– Their metabolism slows down and they exhibit decreasedproduction of bacterial toxins
• They can be removed from the wound in toto
Ljungh A, et al. J Wound Care. 2006;15(4):175-180.
Prophylactic Bacterial Binding
• Preventing the attachment of planktonic microorganisms to the wound surface interferes with the very first stage in biofilm formation
• Encouraging the attachment on an alternative surface reduces the opportunity for formation of microcolonies within the wound itself, preventing the development of the characteristic exopolysaccharide “slime” noted in biofilms
Gristina AG. Science. 1987;237(4822):1588-1595. Schierholz JM, et al. J Hosp Infect. 2001;49(2):87-93.
Many Virulent, MicroorganismsExhibit Hydrophobicity
• Some common microorganisms in infected wounds
– Staphylococcus
– Streptococcus
– Klebsiella
– Citrobacter
– C albicans
Ljungh A, et al. Microbiol Immunol. 1995;39(10):753-757.
Test: Replication of Bound Bacteria
• Dressing samples with bound bacteria
• Incubation for 24 hours
• Result: limited replication occured
Bo
un
dC
ells
/cm
2
108
107
106
Pseudomonas
S aureus
Time (hours)
0 After 24 hours
Ljungh A, et al. J Wound Care. 2006;15(4):175-180.
Rapid and Effective Bacteria Binding
Ce
lls
/cm
2
109
107
106
Time (hours)
After 30 Seconds After 2 Hours
105
104
108
• The in vitro test shows – DACC binds bacteria already within 30 seconds
– After 2 hours, the DACC dressing continues to bind more bacteria
Ljungh A, et al. J Wound Care. 2006;15(4):175-180.
Pseudomonas
S aureus
Reduction ofWound Odor and Exudate Levels
• In a clinical trial on nonhealing wounds bySylvie Hampton, DACC dressings eradicatedmalodor and increasedthe number ofnonodorous wounds
• Exudate levels werereduced considerably
• Highly exuding woundsmoved to moderate exudation within 4 weeksof treatment
43%
28% 28%
73%
27%
0%0
0.10.20.30.40.50.60.70.80.9
1
None Some Odor Malodorous
10%
57%
33%27%
73%
0%0
0.10.20.30.40.50.60.70.80.9
1
Low Moderate High
Per
cen
tP
erce
nt
Hampton S. Wounds UK. 2007;3(4):113-119.
Reduction in Odor
Reduction in Exude Levels
Day 1
Day 28
Day 1
Day 28
Promotion of Wound Healing
• In the Kammerlander trial on 116 colonized and infectedwounds, the DACC dressingeliminated the infection signsin the majority of patients
• Nearly all wounds (93%) improved or healedcompletely in the documentedperiod
• The wound status ofpreviously nonhealing woundsprogressed from black andyellow toward red and pink
72%
21%
6%
1%
4%
14% 14%
38%
14% 14%
4%0% 0% 0%
9%
27%
1%
64%
0102030405060708090
100
Per
cen
t
Kammerlander G, et al. Die Schwester Der Pfleger. 2007;46:84-87. Hampton S. Wounds UK. 2007;3(4):113-119.
Day 1
Day 28
Improved
Cured
Stagnating
Worsened
The Importance of DACC Technology
• Avoids development of microbial resistance
• Avoids cytotoxicity and the release of inflammatorycellular debris
• No demonstrated allergies to DACC
• Avoids systemic contraindications
• Prevents accumulation of bacteria on the wound surface
• Reduces bacterial exo- and endotoxin release
• Safe, simple, cost-effective
Cutting K, et al. J Wound Care. 2011;20(5):1-19.
DACC Dressing Indications
• DACC dressings are effective in all wounds where the primary goal is to remove microorganisms
• Contaminated, colonized, or infected wounds, regardless of their etiology
– Chronic wounds, such as diabetic foot ulcers, leg ulcers, and pressure ulcers
– Postoperative dehisced wounds
– Traumatic wounds
– Wounds after excision or incision of fistula or abscesses
• DACC is also effective against dermal fungal infections
Comparative Study of Two Antimicrobial Dressings in Infected Leg Ulcers: A Pilot Study
• 40 patients were randomly assigned to treatment with a silver hydrofiberdressing or a DACC dressing
• Swab samples from ulcer beds weretaken in order to quantify the bacterial load at inclusion
• Analyzing bacterial load variation showed a significant reduction of bacterial burden on day 4 in both groups
• The silver hydrofiber group had an average bacterial load reduction of 41.6%
• The DACC group had an average reduction of 73.1% (p< 0.00001)
Mosti G, et al. J Wound Care. 2015;24(3):121-127.
Case Studies
DACC with Transformative Foam and TCC on aTransmetatarsal Amputation Ulcer – Weekly Assessments
Diabetic Charcot with Sub-Cuboid UlcerHydrophobic contact layer, Transformative Foam, and
TCC
12-15-13 Original Ulcer Treated with a
Silver Foam and Removable Cast
Walker for Almost 9 months
9-2-14 Patient Agrees to Try TCC – Open toe
design with Hydrophobic Contact
Layer and Transformative Foam
7-24-14 Little Progress After Initial 8 Weeks
Progression During Healing
9-23-2014 10-14-2014 10-21-2014 12-5-2014
Diabetic Ulcer With Undermining
Diabetic Ulcer With Dissecting Hematoma
DACC Over ORC Collagen With Interdigital Maceration
DACC and Super Absorbent DressingOver Post-Op Incision
Questions?
Please do not hesitate to contact meif there is anything at all
that I can do for you:
215-255-5994
Background, Basics and Significance of Silver-Resistance
Phillip J. Finley, PhD
Background and Introduction
• Origin
• Explosion of silver utilization in medicine due to broad-spectrum antimicrobial properties
• Not just used in burn and wound care
• Surgical devices, implants, shunts, catheters, etc
• Concerns of widespread silver resistance have been raised
• Funding – publication
Google-Images. Klasen HJ. Burns. 2000;26(2):117-130. Klasen HJ. Burns. 2000;26(2):131-138. Lansdown AB. J Wound Care. 2002;11(4):125-130. Lansdown AB. J Wound Care. 2002;11(5):173-177. Chopra I. J AntimicrobChemother. 2007;59(4):587-590.
AMP-R
Levo-R
Sil-R
Gent-R
Tobra-R
Cefazo-R
Levo-R = levofloxacin resistance; AMP-R = ampicillin resistance; Gent-R = gentamicin resistance; Tobra-R = tobramycin resistance; Cefazo-R = cefazolin resistance; Sil-R = silver resistance.Gupta A, et al. Nat Med. 1999;5(2):183-188. Gupta A, et al. Microbiology. 2001;147(Pt 12):3393-3402.
Introduction
Genetic Basis for Silver Resistance
Gupta A, et al. Nat Med. 1999;5(2):183-188. Gupta A, et al. Microbiology . 2001;147(Pt 12):3393-3402. Haefeli C, et al. J Bacteriol. 1984;158(1):389-392. Loh JV, et al. Int Wound J. 2009;6(1):32-38. Percival SL, et al. Ostomy Wound Manage. 2008;54(3):30-40. Woods EJ, et al. Vet Microbiol. 2009;138(3-4):325-329.
We know that silver-resistant genes exist
• Plasmid pMG101, isolated from Salmonella
• Since then, sil-genes have been identified in Salmonella, Enterobacter , Escherichia coli, Pseudomonas, Acinetobacter, Klebsiella, and Staphylococcus aureus
Just because genes exist, does not mean they are expressed
• A few cases of bacteria able to grow in toxic levels of silver concentrations
• Pseudomonas stutzeri, originally cultured from a silver mine
• This level of phenotypic silver-resistant expression is unique and remains unseen in clinical bacteria isolated from patients
Initial Bacteria Screening
• Can we even find any?
• Increase probability
250 µM
Cheap Screening Assay
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
67 were capable of luxuriant growth on agar
with 250 µM Ag+
Repeated for 859 isolates collected from patients
250 µM Ag+
Ag = silver ion.Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
32 isolates yieldedpolymerase chain reaction
products for sil + genes20 being from Enterobacter
and Klebsiella
Out of the 67 growers,how many had sil-resistant genes?
Gupta A, et al. Nat Med. 1999;5(2):183-188. Gupta A, et al. Microbiology. 2001;147(Pt 12):3393-3402. Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
Minimum Inhibitory Concentration
• Are any of the 32 isolates expressing the genes?
[Ag] in µM – representative MIC images. Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
Species MIC (µM)
Enterobacter 5500
Klebsiella 5500
Sil +
500 1000 3000 5000 5500
Sil +
0 200 250 300
Scanning electron microscopy/energy dispersive x-ray spectroscopy of same isolate confirming the presence of silver adhered to the cell surface
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
Silver’s Microbiocidal Efficacy
Can be accounted for by three primary mechanisms
1. Silver can bind directly to DNA, interfering with cell replication and transcription
Google-Images. Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
2. Silver can bind to enzymes
3. Silver can bind to the bacterial cell wall, disrupting polysaccharide integrity and membrane fluidity
Quite unique capability
Clinical Significance
Antimicrobial efficacy against silver dressings?
• First looked at them qualitatively
• Corrected zone of inhibition testing
• Secondary cultures
S.
aure
us
GauzeGauzeSilverSilver
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
Silver-SensitiveK pneumoniae
CFU = colony-forming unit.Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
(7 log) 99.99999%
(5 log) 99.999%
(8 log) 99.999999%
(3 log) 99.9%
0%
Lo
g R
ed
uc
tio
n o
f C
FU
/mL
(1 log) 90%
(6 log) 99.9999%
(4 log) 99.99%
(2 log) 99%
Silver-ResistantK pneumoniae
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
(7 log) 99.99999%
(5 log) 99.999%
(8 log) 99.999999%
(3 log) 99.9%
(0%
Lo
g R
ed
uc
tio
n o
f C
FU
/mL
(1 log) 90%
(6 log) 99.9999%
(4 log) 99.99%
(2 log) 99%
Silver-SensitiveE cloacae
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
(7 log) 99.99999%
(5 log) 99.999%
(8 log) 99.999999%
(3 log) 99.9%
(0%
Lo
g R
ed
uc
tio
n o
f C
FU
/mL
(1 log) 90%
(6 log) 99.9999%
(4 log) 99.99%
(2 log) 99%
Silver-ResistantE cloacae
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
(7 log) 99.99999%
(5 log) 99.999%
(8 log) 99.999999%
(3 log) 99.9%
(0%
Lo
g R
ed
uc
tio
n o
f C
FU
/mL
(1 log) 90%
(6 log) 99.9999%
(4 log) 99.99%
(2 log) 99%
Clinical Significance
• Silver-resistant bacteria were at least 1000 X more resistant to commercially available silver-based wound dressings compared with their nonresistant counterparts
• Current Clinical Studies
– Biofilm or silver resistance
– Catheter surveillance
Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
DACC Ability to Bind Silver Resistant Bacteria
Finley PJ, et al. Silver Resistance identified in clinically isolated Enterobacteriaceae: Major Implications for Burn and Wound Care. Presented at 2015 Symposium on Advanced Wound Care; April/May 2015; San Antonio, TX.
Clinical Comments/Criticism
• Only 2 out of 859 isolates (0.2%) were expressing the genes at time of analysis
• But 32 actually had the genes (3.7%)
– Just because they weren’t expressed during testing doesn’t mean they can’t
• Remember, 67 were capable of growth during initial screening (~8.0%)
• We only looked at specific genes in 1 plasmid (there are potentially many different plasmids and genes)
– For example: R478, pAPEC-O1-R, R27, and pUPI199
Gilmour MW, et al. Plasmid. 2004;52(3):182-202. Johnson TJ, et al. Antimicrob Agents Chemother. 2006;50(11):3929-3933. Deshpande LM, et al. Biometals. 1994;7(1):49-56.
Clinical Comments/Criticism
Bacteria can’t share this plasmid above room temperature
Copyright © 2006 Nature Publishing Group. Nature Reviews. Microbiology.
Bacterial Transformation
Bacterial Conjugation
Incompatibility Group HI Plasmids
Maher D, et al. Can J Microbiol. 1993;39(6):581-587. Finley PJ, et al. Identification of Highly Silver-Resistant Clinical Bacteria: Major Implication for Burn and Wound Care. Presented at 2014 Symposium on Advanced Wound Care; October 2014; Las Vegas, Nevada.
Unexpected DNA
Value of Hydrophobic Dressings
• Antimicrobial agent stewardship
• Nonsilver-based dressings
• Foundation of hydrophobic interactions
• Cell surface hydrophobicity
Ljungh A, et al. J Wound Care. 2006;15(4):175-180.
Value of Hydrophobic Dressings
• Sequestering and retention of microorganisms
• Passive mechanism for reduction of bioburden
• Addresses issues of resistance
Bowler PG, et al. J Wound Care. 1999;8(10):499-502.
Conclusions
• First clinical bacteria identified expressing clinically significant silver resistance
• The development of acute silver resistance would have significant consequences on wound care and patient outcomes
• Warning
– Bacteria are resilient – they are going to figure out a way to survive
– Silver antimicrobial stewardship
Q&A