gore antimicrobial technology and medical device infections

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 InfectionsUnited 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

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 = methicillin-resistant S. aureus; MSSA = methicillin-susceptible S. aureus

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 =secure&ip_company_code=CMEZPHY&ip_test_id=8297&ip_cookie=12421183. Accessed August 19, 2005.

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. Gristina AG, Naylor P, Myrvik Q. Infections form biomaterials and implants: a race for the surface. Medical Progress Through Technology 1998;4:205-224.

2. Stamm WE. Infections related to medical devices. Annals of Internal Medicine 1978;89:764-769.3. 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 InfectionA 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;4:205-224.

2. Deysine M. Pathophysiology, prevention, and management of prosthetic infections in hernia surgery. Surgical Clinics of North America 1998;78(6):1105-1115.

“I just can’t go with the flow anymore. I’ve been thinking

about joining a biofilm.”

Bacteria Want to Be in Biofilms

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.

Necrotic Cellular Debris Bacteria Within Debris

Biofilms Can Be Difficult to Detect

• Culture– Short culture times may lead to false

negatives

• Histology– Bacteria can be hidden in biofilm

Biofilm Formation

Center for Biofilm Engineering, Montana State University

Plaque is a Biofilm

Biofilm on ePTFE

RBC

Bacteria (cocci)

Biofilm (slime)

Bruce Wagner, W.L. Gore & Associates, Inc.

ePTFE

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.

2 hours 4 hours

24 hours

Biofilm Formation

8 hours

Betsey Pitts, Center for Biofilm Engineering, Montana State University

3-D Imaging of Biofilm

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 Efficacyof Antimicrobial Technology

Safety of Gore’s Antimicrobial TechnologyClinical 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-agent-impregnated 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 Non-antimicrobial TechnologyTechnology

Antimicrobial Antimicrobial TechnologyTechnology

Colonization of the implant Colonization of the implant surface and interstices. surface and interstices. (H&E stain; 20x magnification)(H&E stain; 20x magnification)

Protection of the implant Protection of the implant surface and interstices from surface and interstices from colonization. colonization. (H&E stain; 20x magnification)(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


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


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;19:430-435.



Significant Values: 1) DM+ < DM, M, X, SM, S, A, P (p=0.05). 2) SM < A (p=0.05). 3) P < A (p=0.05)

0

1

2

3

4

5

6

7

8

DM+ DM M X SM S A P

012345678910

MeanMinMaxMedian

Log10 Values for Wash Count




Log10 Values for Broth Count

0

1

2

3

4

5

6

7

DM+ DM M X SM S A P

0

1

2

3

4

5

6

7

8

MeanMinMaxMedian

Significant Values: 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).



• 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


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. LeBlanc KA. Laparoscopic incisional and ventral hernia repair: complications–how to avoid and handle. Hernia 2004;8(4):323-331.2. 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

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

W. L. Gore & Associates, Inc.Flagstaff, AZ 86004

800.437.8181928.779.2771

goremedical.com

CONTRAINDICATIONS: Patients with hypersensitivity to chlorhexidine or silver;reconstruction of cardiovascular defects; reconstruction of central nervous system orperipheral nervous system defects; pre-term and neonatal populations. WARNINGS: Usewith caution in patients with methemoglobinopathy or related disorders. When used as atemporary external bridging device, use measures to avoid contamination; the entire deviceshould 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 maybe necessary. Improper positioning of the smooth non-textured surface adjacent tofascial or subcutaneous tissue will result in minimal tissue attachment.POSSIBLE ADVERSE REACTIONS: Contamination, infection, inflammation,adhesion, fistula formation, seroma formation, hematoma and recurrence.

gore antimicrobial technology and medical device infections

Documents

aureus infections

implant infections

nosocomial infections

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skin structure infections