Transcript Gore Antimicrobial Technology and Medical Device Infections Outline • Infections and Medical Devices – Incidence and Impact – Role of Biofilms • Gore’s Antimicrobial Technology –

Gore Antimicrobial Technology
and Medical Device Infections
Outline
• Infections and Medical Devices
– Incidence and Impact
– Role of Biofilms
• Gore’s Antimicrobial Technology
– What is It?
– How Does it Work?
– Safety and Efficacy
Infections and
Medical Devices
Hospital-Acquired Infections
United States
• Nearly 2 million nosocomial infections per
year1,2
– ~90,000 deaths
– >70% of the causal bacteria are resistant
• Patients with drug-resistant infections1
– Longer hospital stays
– Treatment with drugs that may be less effective,
more toxic, and/or more expensive
• Nearly $11 billion annually2
1. Campaign to prevent antimicrobial resistance in healthcare settings. Centers for Disease Control and Prevention web site. Available at
http://www.cdc.gov/drugresistance/healthcare/problem.htm. Accessed September 12, 2005.
2. Schierholz JM, Beuth J. Implant infections: a haven for opportunistic bacteria. Journal of Hospital Infection 2001;49:87-93.
Surgical Site Infections
United States
• ~700,000 surgical site infections per year1
• ~$1.6 billion added hospital charges annually2
• One study2:
Outcome
Control
(n=193)
MSSA
(n=165)
MRSA
(n=121)
Death (number)
4
11
25
Hospital stay (days)
5
14
23
Cost (median)
$29,455
$52,791
$92,363
MRSA = methicillin-resistant S. aureus; MSSA = methicillin-susceptible S. aureus
1. Nathens AB, Dellinger EP. Surgical site infections. Current Treatment Options in Infectious Diseases 2000;2:347-358.
2. Engemann JJ, Carmeli Y, Cosgrove SE, et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with
Staphylococcus aureus surgical site infection. Clinical Infectious Diseases 2003;36:592-598.
MRSA
• Prevalence1,2
– Precipitous rise
– 43% of hospital S. aureus infections
– 28% of surgical site infections
• Problems1,2
– Generally multi-drug resistant
– MRSA only susceptible to vancomycin grew from
23% to 56% in 10 years
– Resistance to vancomycin has emerged
1. Kuehnert MJ, Hill HA, Kupronis BA, Tokars JI, Solomon SL, Jernigan DB. Methicillin-resistant–Staphylococcus aureus hospitalizations, United States.
Emerging Infectious Diseases [serial online] 2005;11(6). Available at: http://www.cdc.gov/ncidod/EID/vol11no06/04-0831.htm. Accessed September 12,
2005.
2. Fry DE. Complicated skin and skin structure infections caused by hospital- and community-acquired MRSA: What surgeons need to know [CME course on
the Internet]. Available at: http://www.cmezone.com/ce-bin/owa/pkg_ disclaimer_html.display?ip_mode
Medical Device Infections
• 1-6% of implanted medical devices become
infected1
– Account for ~45% of nosocomial infections2
• Ventral Hernia Repair3
– Open 7-18%
– Laparoscopic 0-2%
• Timeframe
– Short term – within first 10 days
– Long term – up to several years post op
1.
2.
3.
Gristina AG, Naylor P, Myrvik Q. Infections form biomaterials and implants: a race for the surface. Medical Progress Through Technology 1998;4:205-224.
Stamm WE. Infections related to medical devices. Annals of Internal Medicine 1978;89:764-769.
Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:430-435.
Consequences of Device Infections
• Increased
–
–
–
–
–
–
Pain and discomfort
Hospital stay
Healing/recovery time
Cost
Morbidity
Mortality
• May require additional
surgery to remove
device
Infected polypropylene mesh
seven months post operatively.
Pathogenesis of Infection
A Race for the Surface1,2
• Bacteria introduced primarily at time of
implant or in the immediate post-op period
–
–
–
–
–
Patient’s own skin flora
Pre-existing infection at distant site
Hospital environment
Surgical staff
Supporting therapy (IV, etc.)
• Bacteria adhere to and colonize device
– Bacteria can produce their own protective biofilm
– Bacteria evade conventional antibiotic therapy
and patient’s immune response
1.
Gristina AG, Naylor P, Myrvik Q. Infections from biomaterials and implants: a race for the surface. Medical Progress Through Technology 1998;4:205224.
Bacteria Want to Be in Biofilms
“I just can’t go with the flow
anymore. I’ve been thinking
about joining a biofilm.”
Center for Biofilm Engineering, Montana State University
Biofilms
What Are Biofilms and
Why Are They Important?
• Biofilm
– Bacteria in a self-excreted slimy substance adhered
to a surface1
• Bacteria in biofilms2
– No longer planktonic
– Act as a community
– Often multiple species
• Estimated 65% of human infections involve
biofilms3
– Provide protection from host’s immune response
– Can require 1000x antibiotic concentration to kill
versus planktonic2
1. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 1999;284:1318-1322.
2. What being in a biofilm means to bacteria. The Center for Biofilm Engineering at Montana State University Web Site. Available at:
http://www.erc.montana.edu/CBEssentials-SW/bf-basics-99/bbasics-bfcharact.htm. Accessed September 26, 2005.
3. Cvitkovitch DG, Li Y-H, Ellen RP. Quorum sensing and biofilm formation in Streptococcal infections. Journal of Clinical Investigation 2003;112:1626-1632.
Biofilms Can Be Difficult to Detect
• Culture
– Short culture times may lead to false negatives
• Histology
– Bacteria can be hidden in biofilm
Necrotic Cellular Debris
Bacteria Within Debris
Biofilm Formation
Center for Biofilm Engineering, Montana State University
Biofilm Formation
Center for Biofilm Engineering, Montana State University
Plaque is a Biofilm
Biofilm on ePTFE
ePTFE
Bacteria (cocci)
Biofilm (slime)
RBC
Bruce Wagner, W.L. Gore & Associates, Inc.
Biofilm Formation
2 hours
4 hours
8 hours
24 hours
Olson ME, Ruseka I, Costerton JW. Colonization of n-butyl-2-cyanoacrylate tissue adhesive by Staphylococcus epidermidis. Journal of Biomedical Materials
Research 1988;22:485-495.
3-D Imaging of Biofilm
Betsey Pitts, Center for Biofilm Engineering, Montana State University
Clinical Impact of Biofilms
• Two main infection scenarios
– Short term – within 10 days
– Long term – up to several years post op
• Treatment progression
– Broad spectrum and/or specific antibiotics
– Wound does not heal and is culture negative
– Device is removed
The Challenge
Protect the
device from
colonization at
time of implant.
Gore’s Solution
• Device coating as first line of defense against
bacterial colonization
– Resist bacterial adherence
– Effective against a broad spectrum of bacteria
• Local rather than systemic exposure
– Small amounts of agents
– Protect device, not treat surrounding tissue
• Agents not typically used to treat infections
– Does not affect choice of local or systemic antibiotics
– Minimal tendency toward resistance
Gore’s Antimicrobial Technology
Gore’s Antimicrobial Technology
• What is it?
– Synergistic combination of two antimicrobial agents,
silver and chlorhexidine
• Silver
– Binds with and destroys bacterial cell proteins,
causing loss of normal biological function
• Chlorhexidine
– Permeates bacterial cell wall causing disruption and
leakage of the cell contents
What Does Antimicrobial Technology Do?
Inhibits bacterial
colonization of, and
resists initial biofilm
formation on, the device
for up to 14 days post
implantation.
Safety and Efficacy
of Antimicrobial Technology
Safety of Gore’s Antimicrobial Technology
Clinical Experience
• Short-term study1
– 37 patients; controlled, randomized
– PLUS products do “not appear to produce any
adverse systemic or clinical effects after hernia
repair”
• Almost 10 years and over 150,000 implants
– To date no confirmed reports of hypersensitivity
1. DeBord JR, Bauer JJ, Grischkan DM, LeBlanc KA, Smoot Jr. RT, Voeller GR, Weiland LH. Short-term study on the safety of antimicrobial-agentimpregnated ePTFE patches for hernia repair. Hernia 1999;3:189-193.
In-Vitro Efficacy of Gore’s Antimicrobial
Technology
• Zone of inhibition bioassays
• Substantial antimicrobial
activity against gram-positive
and gram-negative organisms
–
–
–
–
–
–
–
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa
Klebsiella pneumoniae
Staphylococcus epidermidis
Candida albicans
Methicillin-resistant Staphylococcus
aureus (MRSA)
– Vancomycin-resitant enterococcus
faecalis
– Group A Streptococcus
– Acinetobacter baummanii
In-Vivo Efficacy of Gore’s Antimicrobial
Technology
• Rabbit model 10 days post-inoculation with S.
aureus
Non-antimicrobial
Technology
Colonization of the implant
surface and interstices.
(H&E stain; 20x magnification)
Antimicrobial Technology
Protection of the implant
surface and interstices from
colonization.
(H&E stain; 20x magnification)
Susceptibility to MRSA Adherence
• AG Harrell, American
Hernia Society Meeting,
Feb. 2005
– Compared MRSA
adherence to various types
of meshes using an in-vitro
model
• Methods
– Inoculated with 108 MRSA
in tryptic soy broth
– Incubated for 1 hour at 37
oC
– Washed and counted CFU
in wash and broth
– SEM of meshes
• Products tested
– GORE DUALMESH® PLUS
Biomaterial
– GORE DUALMESH®
Biomaterial
– Bard® Mesh
– Bard® COMPOSIX® E/X Mesh
– PROCEED™ Surgical Mesh
– PARIETEX® COMPOSITE
Mesh
– TiMESH Mesh-Implant
– ULTRAPRO™ Mesh
– VYPRO™ Mesh
Harrell AG. Prosthetic mesh biomaterial susceptibility to methicillin resistant Staphylococcus aureus adherence in an in-vitro model. Abstract presented at
Hernia Repair 2005. American Hernia Society. San Diego, CA. Feb 9-12, 2005. Page 94. Abstract 36F.
Results of MRSA Adherence
GORE DUALMESH®
PLUS Biomaterial
Harrell AG. Prosthetic mesh biomaterial susceptibility to methicillin resistant Staphylococcus aureus adherence in an in-vitro model. Abstract presented at
Hernia Repair 2005. American Hernia Society. San Diego, CA. Feb 9-12, 2005. Page 94. Abstract 36F.
Susceptibility to MRSA Adherence
• GORE DUALMESH® PLUS Biomaterial
– No detectable MRSA in the broth or the pooled wash
samples
– SEM confirmed bacterial adherence to all other mesh
types
– Only mesh type in the nine tested that demonstrated
a bactericidal property
Harrell AG. Prosthetic mesh biomaterial susceptibility to methicillin resistant Staphylococcus aureus adherence in an in-vitro model. Abstract presented at
Hernia Repair 2005. American Hernia Society. San Diego, CA. Feb 9-12, 2005. Page 94. Abstract 36F.
Mesh Susceptibility to Infection
• AM Carbonell et al, Surg
Endosc 2005
– Determine the
susceptibility of mesh to S.
aureus infection in a rat
model
• Methods
– Created 2 cm2 hernia
defect and sutured mesh
to it
– Inoculated each mesh with
108 penicillin-sensitive S.
aureus
– 5 day incubation
– Harvested biomaterials
sterilely, washed, cultured,
counted CFU
• Meshes tested
– GORE DUALMESH®
PLUS Biomaterial
– GORE DUALMESH®
Biomaterial
– Bard® Mesh
– Bard® COMPOSIX® Mesh
– SEPRAMESH™
Biosurgical Composite
– SURGISIS® Soft Tissue
Graft
– ALLODERM®
Regenerative Tissue
Matrix
Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:430-
Mesh Susceptibility to Infection
Log10 Values for Wash Count
8
7
GORE DUALMESH®
PLUS Biomaterial
10
9
8
7
6
5
4
3
2
1
0
6
5
4
3
2
1
0
DM+
DM
Significant Values:
M
X
SM
S
A
Mean
Min
Max
Median
P
1) DM+ < DM, M, X, SM, S, A, P (p=0.05).
2) SM < A (p=0.05).
3) P < A (p=0.05)
Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:430-435.
Mesh Susceptibility to Infection
Log10 Values for Broth Count
7
6
5
8
7
GORE DUALMESH®
PLUS Biomaterial
6
5
4
4
3
3
2
Mean
Min
Max
Median
2
1
1
0
0
DM+
DM
Significant Values:
M
X
SM
S
A
P
1) DM+ < DM, M, X, SM, S, A, and P (p=0.05).
2) P < DM, M, X, SM, S, and A (p=0.05).
Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:430-435.
Mesh Susceptibility to Infection
• GORE DUALMESH® PLUS Biomaterial
– Was the least susceptible to infection
– Able to kill all the inoculated bacteria in a live-animal
study of mesh infection
• Silver/chlorhexidine meshes
– May be the prosthetics of choice to minimize
occurrence of mesh infection
Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:430-435.
Clinical Experience with Gore’s
Antimicrobial Technology
Laparoscopic Ventral Hernia Repair
• KA LeBlanc, MD, MBA, FACS1
– The use of GORE DUALMESH® PLUS Biomaterial
“appears to anecdotally decrease the rate of
infections. We have not encountered a postoperative
infection when this prosthesis was used.”
• AM Carbonell et al.2
– 268 laparoscopic ventral hernia repairs using ePTFE
– Two mesh infections, neither of which occurred with
GORE DUALMESH® PLUS Biomaterial
1.
2.
LeBlanc KA. Laparoscopic incisional and ventral hernia repair: complications–how to avoid and handle. Hernia 2004;8(4):323-331.
Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:430-435.
Summary
• Medical Device Infections
– Increase morbidity, mortality, cost, etc.
– Biofilm formation makes diagnosis and treatment
difficult
– The best treatment is prevention
• Gore’s Antimicrobial Technology
– Inhibits bacterial colonization for up to 14 days post
implantation
– Currently available in devices used for soft tissue
repair
Considerations
• Do NOT alter usual practice of pre-, peri-, or post-operative
administration of local or systemic antibiotics
• NOT recommended for contaminated fields
• NOT for treatment of infection
• NOT for patients with hypersensitivity to chlorhexidine or silver
• NOT for pre-term and neonatal populations
CONTRAINDICATIONS: Patients with hypersensitivity to chlorhexidine or silver;
reconstruction of cardiovascular defects; reconstruction of central nervous system or
peripheral nervous system defects; pre-term and neonatal populations. WARNINGS: Use
with caution in patients with methemoglobinopathy or related disorders. When used as a
temporary external bridging device, use measures to avoid contamination; the entire device
should be removed as early as clinically feasible, not to exceed 45 days after placement.
When unintentional exposure occurs, treat to avoid contamination or device removal may
be necessary. Improper positioning of the smooth non-textured surface adjacent to
fascial or subcutaneous tissue will result in minimal tissue attachment.
POSSIBLE ADVERSE REACTIONS: Contamination, infection, inflammation,
adhesion, fistula formation, seroma formation, hematoma and recurrence.
W. L. Gore & Associates, Inc.
Flagstaff, AZ 86004
800.437.8181
928.779.2771
goremedical.com
Product(s) listed may not be available in all markets pending regulatory clearance.
GORE, DUALMESH®, DUALMESH® PLUS, and designs are trademarks of W. L. Gore & Associates. ALLODERM® is a trademark of LifeCell Corporation. BARD®, MARLEX®, and COMPOSIX® are trademarks
of C. R. Bard, Inc. PARIETEX® is a trademark of Sofradim Production, Inc. PROCEED®, ULTRAPRO®, and VYPRO are trademarks of Ethicon, Inc. SEPRAMESH® is a trademark of Genzyme Corporation.
SURGISIS® is a trademark of Cook Biotech, Inc. TIMESH® is a trademark of Medtronic, Inc.
© 2007 W. L. Gore & Associates, Inc. AJ1857-EN3 MAY 2007