1. Biomaterial Related Infection
Titik Nuryastuti
Microbiology Dept.,
Fac. of Medicine, UGM

2. Structural biological materials
Hard Tissues: Bone, enamel, dentin
Soft Tissues: Cartilage, tendon, ligament, vitreous humor,vasculature,skin, organs
Fluids: Blood, synovial fluid
Problems when used as an implant material: Infection, resorption, inflammation, rejection 2

3. Implant Factors
Bulk properties: chemical composition, structure, purity and presence of leachables.
Surface properties: smoothness, geometry, hydrophilicity, and surface charge
Mechanical properties: match properties of component being replaced, such as elastic modulus. Stability and fixation.
Long-term structural integrity: design for fatigue and fracture loading, wear, creep, plastic deformation, and stress corrosion cracking 3

4. Host Factors
Species (simulated tests in smaller species do not always capture response in humans)
Age and health status
Immunological/metabolic status 4

5. Biocompatibility
Arises from differences between living and non-living materials
Bioimplants trigger inflammation or foreign body response
New biomaterials must be tested prior to implantation according to FDA regulation 5

6. Foreign Body Response
Rapid dilation of capillaries, increased permeability of endothelial cell linings and cell reactions
Macrophages release degradative enzymes (lysozymes) that attempt to digest the foreign material
Macrophages multiply (Mitosis) and serve as progenitor to the giant cell
Undigestable: frustrated phagocytosis. Size scale is important. 6

7. Response to inflammation
Decreased tissue mass and formation of new tissue through granulation
Collagen and other molecules are synthesized
Formation of scar tissue
Remodeling process differs for various tissues 7

8. Challenges Biofixation and stability of an implant
Long-term wear and debris generation
In-vivo degradation through complex bio-chemi-mechanical actions
Inert materials do not elicit “pro-active” responses in the body
Solutions are often temporary for tissue replacement 8

9. Current Trends
Interdisciplinary approach: merge engineering, biology, and materials science
Engineer new biological and hybrid materials
Develop “smart” or “pro-active” materials which can assist in tissue regeneration or treatment 9

10. Implant Associated Infections & Sterilization Methods
Frequently, presenters must deliver material of a technical nature to an audience unfamiliar with the topic or vocabulary. The material may be complex or heavy with detail. To present technical material effectively, use the following guidelines from Dale Carnegie Training®.
Consider the amount of time available and prepare to organize your material. Narrow your topic. Divide your presentation into clear segments. Follow a logical progression. Maintain your focus throughout. Close the presentation with a summary, repetition of the key steps, or a logical conclusion.
Keep your audience in mind at all times. For example, be sure data is clear and information is relevant. Keep the level of detail and vocabulary appropriate for the audience. Use visuals to support key points or steps. Keep alert to the needs of your listeners, and you will have a more receptive audience.
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11. Infectious Agents microscopic organisms, including bacteria, viruses,
Fungi, and
animal parasites,
they penetrate the body’s natural barriers and multiply to create symptoms
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12. Implant associated Infections
The benefits of implanted devices are often limited by the occurrence of infections associated with the devices, even when the best aseptic techniques are practiced;
Each year, as many as 2 million hospital patients in the United States develop device related infections at a cost of nearly $11 billion annually;
Approximately 80% of the 80,000 annual deaths in this country that result from infections that are device related;
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13. Nosocomial Infections
Infections that are acquired while a patient is in a hospital are referred to as nosocomial infections; a term derived from 'nosos' the Greek word for 'disease'.
Nosocomial infections are diseases that heath care professionals give to their clients.
Device-related infection results from the introduction of organisms, primarily bacteria, during the device insertion or implantation procedure, or from attachment of bloodborne organisms to the newly inserted device and their subsequent propagation on its surface.

14. Nosocomial Infections -continued
Infection also can occur after insertion, either from bacteria in the blood or urine attaching to the device or, in the case of externally communicating devices, from bacteria that use the device as a pathway into the body, in some cases long after the device has been inserted.

15. Urinary Catheters
Urinary-tract infections occur in about 20% of patients with Foley catheters in place for more than 10 days;
and in more than 40% of patients with Foley catheters in place for more than 25 days.
There are approximately 500,000 cases of these infections in U.S. hospitals each year, and most are associated with catheters.
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16. Central Venous Catheters
bloodstream infections in the United States number more than 100,000 per year, with annual mortality ranging from 10,000 to 20,000 and cost of treatment estimated at $1 billion;
At least 50,000 cases of these infections are associated with central venous catheters; and,
Other IV devices, such as midline catheters and peripherally inserted central catheters (PICCs), also cause for significant level of infections.
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17. Blood Stream Infections
Migration of skin organisms at the insertion site into the cutaneous catheter tract with colonization of the catheter tip is the most common route of infection for peripherally inserted, short-term catheters;
Contamination of the catheter hub contributes substantially to intraluminal colonization of long-term catheters;
Occasionally, catheters might become hematogenously seeded from another focus of infection; and,
Rarely, infusate contamination leads to BSI
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18. Infectious Agents
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19. 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:

21. 1. Free-floating, or planktonic, bacteria encounter a submerged surface and within minutes can become attached. They begin to produce slimy extracellular polymeric substances (EPS) and to colonize the surface.
2. EPS production allows the emerging biofilm community to develop a complex, three-dimensional structure that is influenced by a variety of environmental factors. Biofilm communities can develop within hours.
3. Biofilms can propagate through detachment of small or large clumps of cells, or by a type of "seeding dispersal" that releases individual cells. Either type of detachment allows bacteria to attach to a surface or to a biofilm downstream of the original community.

22. Aerobic, Gram-positive cocci
Staphylococcus aureus
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23. Glucose-nonfermenting, Gram-negative rods
Pseudomonas aeruginosa
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24. Types of Infectious Agents
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25. Devices and Types of Infections
Sutures -Staphylococcus epidermidis and S. aureus
Exit sites-S. epidermidis and S. aureus
Contact lens-P. aeruginosa and Gram-positive cocci
Urinary catheter-E. coli and other Gram-negative rods
Peritoneal dialysis (CAPD) peritonitis -A variety of bacteria and fungi
Endotracheal tubes -A variety of bacteria and fungi
Mechanical heart valves-S. epidermidis and S. aureus
Vascular grafts -Gram-positive cocci
Orthopedic devices - S. epidermidis and S. aureus
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27. Biofilms are playing an increasingly important role in the spread of nosocomial infections because:
Increasingly aggressive medical and surgical interventions (implants, organ transplants, device use) places patients at a higher risk

28. Prevention & Sterilization
Frequently, presenters must deliver material of a technical nature to an audience unfamiliar with the topic or vocabulary. The material may be complex or heavy with detail. To present technical material effectively, use the following guidelines from Dale Carnegie Training®.
Consider the amount of time available and prepare to organize your material. Narrow your topic. Divide your presentation into clear segments. Follow a logical progression. Maintain your focus throughout. Close the presentation with a summary, repetition of the key steps, or a logical conclusion.
Keep your audience in mind at all times. For example, be sure data is clear and information is relevant. Keep the level of detail and vocabulary appropriate for the audience. Use visuals to support key points or steps. Keep alert to the needs of your listeners, and you will have a more receptive audience.
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29. Biofilm Formation the biological mechanisms are poorly understood
therefore mitigating strategies have to focus decreasing initial bioburden
A key to biofilm formation appears to be the interaction between the body and the implant — more specifically, the interface between the biomaterial surface and the bacteria as well as the associated environments (for example, plasma proteins deposited onto the implant material surface can “condition” the surface for biofilm formation).
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30. A Prosthesis Related Infection is Difficult to Treat
standard antibiotic protocols fail to achieve a cure
reduced sensitivity of the bacteria growing in the biofilm
relatively poor availability of antibiotics from the blood stream
formation of a biomaterial- associated biofilm (irreversible infection) usually leads to removal or revision of the affected device or implant
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31. Prevention
Good clinical practice—such as thoroughly cleaning and disinfecting the area prior to insertion, proper prepping by the clinical staff, and care in handling the device to maintain sterility prior to insertion—will reduce but not eliminate the occurrence of infection
Aseptic procedure for all health care worker
Monitoring number of bacterial room (OR)
Developing “smart biomaterial” for ideal devices

32. Sterilization or Disinfection of Medical Devices: General Principles
In general, reusable medical devices or patient-care equipment that enters normally sterile tissue or the vascular system or through which blood flows should be sterilized before each use.
Sterilization means the use of a physical or chemical procedure to destroy all microbial life, including highly resistant bacterial endospores.
The major sterilizing agents used in hospitals are a) dry heat, b) moist heat by steam autoclaving, c) ethylene oxide gas, and, d) radiation.
Disinfection means the use of a chemical procedure that eliminates virtually all recognized pathogenic microorganisms but not necessarily all microbial forms (e.g., bacterial endospores) on inanimate objects.
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33. Thank you