Presentation is loading. Please wait.

Presentation is loading. Please wait.

Gore Antimicrobial Technology and Medical Device Infections

Similar presentations


Presentation on theme: "Gore Antimicrobial Technology and Medical Device Infections"— Presentation transcript:

1 Gore Antimicrobial Technology and Medical Device Infections

2 Outline Infections and Medical Devices Gore’s Antimicrobial Technology
Incidence and Impact Role of Biofilms Gore’s Antimicrobial Technology What is It? How Does it Work? Safety and Efficacy

3 Infections and Medical Devices

4 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 Campaign to prevent antimicrobial resistance in healthcare settings. Centers for Disease Control and Prevention web site. Available at Accessed September 12, 2005. Schierholz JM, Beuth J. Implant infections: a haven for opportunistic bacteria. Journal of Hospital Infection 2001;49:87-93.

5 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 The Engemann report was of a prospective, cohort study. The statistically significant differences between groups were: Mortality: Higher MRSA vs control (p<.001) and MRSA vs MSSA (p<.001) Hospitalization after surgery: Higher MSSA vs control, MRSA vs control, and MRSA vs MSSA (p<.001 for each) Hospitalization after infection: Higher MRSA (15 days) vs MSSA (10 days) (p=.001) Costs: Higher for MSSA vs control, MRSA vs control, and MRSA vs MSSA (p<.001 for each) MRSA = methicillin-resistant S. aureus; MSSA = methicillin-susceptible S. aureus Nathens AB, Dellinger EP. Surgical site infections. Current Treatment Options in Infectious Diseases 2000;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:

6 MRSA Prevalence1,2 Problems1,2 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 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: Accessed September 12, 2005. 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: disclaimer_html.display?ip_mode =secure&ip_company_code=CMEZPHY&ip_test_id=8297&ip_cookie= Accessed August 19, 2005.

7 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 The 1-6% is an overall average for all implanted medical devices. There are higher and lower examples. Gristina AG, Naylor P, Myrvik Q. Infections form biomaterials and implants: a race for the surface. Medical Progress Through Technology 1998;4: Stamm WE. Infections related to medical devices. Annals of Internal Medicine 1978;89: Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:

8 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.

9 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 Despite one’s best efforts, some bacteria almost always find their way into wounds and onto implanted medical devices. According to Schierholz JM, Beuth J (Implant infections: a haven for opportunistic bacteria. Journal of Hospital Infection 2001;49:87-93.): It is impossible to create a predictably sterile wound, even under laminar flow. S. aureus can be recovered from ~90% of clean wounds at time of closure. Minor contamination of implant area may be regarded as a physiological phenomenon. An implant lowers the threshold of infection and generates local immunosuppression Gristina AG, Naylor P, Myrvik Q. Infections from biomaterials and implants: a race for the surface. Medical Progress Through Technology 1998;4: Deysine M. Pathophysiology, prevention, and management of prosthetic infections in hernia surgery. Surgical Clinics of North America 1998;78(6):

10 Bacteria Want to Be in Biofilms
“I just can’t go with the flow anymore. I’ve been thinking about joining a biofilm.” Biofilms are a safe haven for bacteria as they help them survive in a harsh environment. Center for Biofilm Engineering, Montana State University

11 Biofilms

12 What Are Biofilms and Why Are They Important?
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 Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 1999;284: What being in a biofilm means to bacteria. The Center for Biofilm Engineering at Montana State University Web Site. Available at: Accessed September 26, 2005. Cvitkovitch DG, Li Y-H, Ellen RP. Quorum sensing and biofilm formation in Streptococcal infections. Journal of Clinical Investigation 2003;112:

13 Biofilms Can Be Difficult to Detect
Culture Short culture times may lead to false negatives Histology Bacteria can be hidden in biofilm Typical culture times in a hospital lab are 24 hours. It may take up to a week of culturing to see growth by bacteria in a biofilm due to their sessile state. The two pictures are of an infected clinical sample. In a typical H&E or Gram stain (left) you may see necrotic cellular debris without being able to see cells because the biofilm doesn’t stain well (glycocalyx blocks the stain). But if you use TEM (right), you can clearly see the bacterial cells within the debris. It may require special training of histologists for them to correctly identify biofilms. Necrotic Cellular Debris Bacteria Within Debris

14 Biofilm Formation When a medical device is implanted, it is “a race for the surface” between bacteria and host cells. If the host cells win the race, they are attached to or integrated into the surface of the device and help to protect it. If the bacteria win the race, they tend to form a biofilm and are very difficult to eradicate without removing the device. Center for Biofilm Engineering, Montana State University

15 Biofilm Formation Biofilm resistance to antimicrobial agents (taken from 1. Antimicrobial depletion in bulk fluid 2. Transport limitation of antimicrobial penetration 3. Physiological limitation of antimicrobial efficacy (at least some of the bacteria adopt a resistant state or phenotype) Center for Biofilm Engineering, Montana State University

16 Plaque is a Biofilm

17 ePTFE Bacteria (cocci) Biofilm (slime) RBC
Biofilm on ePTFE ePTFE Bacteria (cocci) Biofilm (slime) This is an SEM of an infected ePTFE clinical device. The colonizing bacteria is S. epidermidis. RBC Bruce Wagner, W.L. Gore & Associates, Inc.

18 Biofilm Formation 2 hours 8 hours 24 hours 4 hours
These pictures are from an in-vitro study on a “plastic surface” using a strain of S. epidermidis from a patient with endocarditis. The important point is that within 24 hours a full biofilm can develop on a device surface. 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:

19 3-D Imaging of Biofilm Using specialized techniques, biofilms can be imaged in three dimensions. In this video, there is an ePTFE film on top (not visible) and the biofilm has grown below it. The ePTFE film was exposed to a substantial amount of bacteria in an in-vitro model, somewhat analogous to an infected field clinically. Betsey Pitts, Center for Biofilm Engineering, Montana State University

20 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 Both short-term and long-term infections can be attributed to biofilms. In the short term, the device becomes colonized and treatment is not effective due to the resilience of the biofilm. In the long term, the bacteria may form a biofilm at implant and remain dormant until some stimulus causes them to become active.

21 Protect the device from colonization at time of implant.
The Challenge Protect the device from colonization at time of implant.

22 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 The rationale for why Gore’s PLUS technology has a minimal tendency toward resistance is: Only a small population of bacteria, those introduced at implantation, are exposed to the agents for a short period of time PLUS agents are not mainstream therapeutic antibiotics The mechanism of action is mechanical, not a target for a specific site of bacterial growth Combination of two antimicrobials with different mechanisms that are synergistic and complimentary

23 Gore’s Antimicrobial Technology

24 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

25 What Does Antimicrobial Technology Do?
Inhibits bacterial colonization of, and resists initial biofilm formation on, the device for up to 14 days post implantation.

26 Safety and Efficacy of Antimicrobial Technology

27 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 In this clinical study, blood samples were taken pre- and post-op at 1, 6, and ~12 weeks. 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:

28 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 The two example zone of inhibition plates are clinical isolates of S. aureus and E. coli from Flagstaff Medical Center. Also note that C. albicans is a yeast.

29 In-Vivo Efficacy of Gore’s Antimicrobial Technology
Rabbit model 10 days post-inoculation with S. aureus Non-antimicrobial Technology Antimicrobial Technology Colonization of the implant surface and interstices. (H&E stain; 20x magnification) Protection of the implant surface and interstices from colonization. (H&E stain; 20x magnification)

30 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 American Hernia Society. San Diego, CA. Feb 9-12, Page 94. Abstract 36F.

31 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 American Hernia Society. San Diego, CA. Feb 9-12, Page 94. Abstract 36F.

32 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 American Hernia Society. San Diego, CA. Feb 9-12, Page 94. Abstract 36F.

33 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 PLUS has been tested in numerous animal studies. This is a recent one not sponsored by Gore. Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:

34 Mesh Susceptibility to Infection
Log10 Values for Wash Count GORE DUALMESH® PLUS Biomaterial 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) Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:

35 Mesh Susceptibility to Infection
Log10 Values for Broth Count 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 Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:

36 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:

37 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 LeBlanc KA. Laparoscopic incisional and ventral hernia repair: complications–how to avoid and handle. Hernia 2004;8(4): Carbonell AM, Matthews BD, Dreau D, et al. The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 2005;19:

38 Summary Medical Device Infections Gore’s Antimicrobial Technology
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

39 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 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


Download ppt "Gore Antimicrobial Technology and Medical Device Infections"

Similar presentations


Ads by Google