Advancements in medical technology and an aging population are two factors that are leading to a rapid expansion in the use of medical devices, a market that is predicted to double over the next ten years. Coupled with the reality that half of all Americans suffer from one or more chronic diseases (e.g., diabetes, cancer, or heart disease), there is an increasing demand for implanted medical devices that can perform longer-term with reduced complications. Mechanical improvements to these devices have been dramatic, yet improvements in controlling the interface between the body and the device have been minimal. As a result, nearly half of all medical devices implanted in the body are plagued with one or more severe complications – such as infection, thrombosis, improper healing, and cell overgrowth.
Ironically, because of the general improvement in the delivery of healthcare, these complications are on the rise. Consider that from 1980 to 2002:
• Life expectancy increased by more than three years.
• Death from heart attack plummeted by 50%.
• Death from stroke dropped 30%.
• Death from breast cancer dropped 20%.
• Disability among the elderly declined by 25%.
These statistics are encouraging, yet the increasing use of medical devices has led to additional occurrences of major complications. There is a significant need to keep medical device surfaces clean for extended periods of time in the body.
Statistics on the threat of healthcare associated infections (HAI), particularly device complications, underlie a legitimate concern on the part of patients and clinicians:
Healthcare Associated Infections result in 99,000 U.S. preventable deaths annually – more deaths than AIDS, auto accidents, and breast cancer deaths combined.
• The majority of the 1.7 million HAIs contracted each year by Americans originate with the colonization (adherence of bacteria) of implantable medical devices – such as catheters – which provide a source of contamination and a surface for microorganism growth.
• The growing epidemic of HAIs, coupled with the rising prevalence of drug resistant organisms, has received increasing attention in recent years. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) has increased over the past several decades from 2% in 1964 to 64% in 2003. MRSA is even more prevalent in the developing world, with an incidence of 84% among common hospital acquired infections.
‣ When an infection reaches the bloodstream, it lengthens average hospital stays by approximately two weeks, costs up to $50,000 to treat, and increases mortality by up to 25 percent, resulting in nearly $30 billion per year in direct medical expenses every year.
Bacteria introduced either through the inside or outside of the catheter can attach to the surface or multiply to form complex biofilms, or communities of microorganisms in which cells adhere to each other and/or to the surface of the catheter.
‣ Studies suggest that thrombosis acts as a focal point for catheter biofilm.
‣ Once established, these protective biofilms are catalysts for infection. They are generally resistant to the immunological response and traditional antibiotics, due to the biofilms' physical “shielding” effect, allowing bacteria to conceal themselves.
The successful development of a long-lasting antimicrobial and anti-thrombogenic vascular access catheter could potentially save thousands of lives and associated treatment costs.
• The continuous development of antibiotic resistance to certain bacteria and the lack of novel antibiotics render the treatment of HAIs increasingly difficult.
• The severity of this problem is validated by its inclusion on the Institute of Medicine’s Comparative Effectiveness Research priority topics list:
‣ Compare the effectiveness of strategies (e.g., bio-patches, reducing central line entry, chlorhexidine for all line entries, antibiotic impregnated catheters, treating all line entries by way of a sterile field) for reducing health care associated infections; including catheter-associated bloodstream infection, ventilator associated pneumonia, and surgical site infections in children and adults.
Catheter infections represent the eighth leading cause of death in the US (costing $11 billion per year) and lengthen average hospital stays by two weeks (up to $50,000 to treat).
• Device complications represent a significant problem for hemodialysis patients: 20% will develop a catheter-related infection, and bloodstream infections are the 2nd leading cause of death. Also, thrombosis (blood clot formation) leads to complete occlusion in 25% of patients. The loss of vascular access is a direct threat to a patient’s life. Infection and clotting are highly interrelated since bacteria can proliferate from a clot. There is a need to prevent both for duration of catheter use.
• Central venous catheters (CVCs), used to administer long-term intravenous antibiotics, drugs for chemotherapy treatment, and dialysis account for an estimated 90% of all catheter-related bloodstream infections (CRBSI).
• Once a “foreign body” such as a catheter is implanted into the blood stream, an immediate biological response begins. Within seconds, blood proteins and host cells (such as platelets) begin to deposit on the device surface, leading to the formation of a large, complex thrombus on the surface.
• “Openness” or patency to blood flow is a critical concern for catheters, vascular grafts, and stents. Thrombus formation on the surface of these devices can constrict or block flow entirely, often requiring costly device replacement and increasing the risk of severe complications and death.
• Thrombosis can clog up to 25% of catheters.
• Similar to infection, the loss of vascular access due to thrombosis directly threatens a patient’s lifeline by placing them at the fatal risk of missing dialysis, sessions until a new source of access is established.
‣ The processes leading to thrombus formation and infection are interrelated, necessitating the development of a novel dual-functional approach to directly mitigate both phenomena.
The interaction of device surfaces with the surrounding tissues is critical for implants:
• Improper healing can necessitate device removal.
• Despite recent advances in orthopedic joint implants, these implants have a high failure rate when implanted into osteoporotic bones that do not fully integrate into the implant surface.
• Inflammation surrounding intravenous catheters (known as phlebitis) is a common cause of discomfort and device replacement.
• Contracture of breast implants is caused by the excessive formation of a “fibrous capsule” as the body attempts to isolate
the foreign body. Excessive encapsulation can cause cosmetic changes, pain, and eventually necessitate device
‣ Engineering the device surface to closely mimic the properties of the surrounding tissue may help prevent these complications by reducing the foreign body response.
Hyperplasia, or cell overgrowth, often leads to device failure:
• The use of pharmaceuticals known as “restenosis inhibitors” in the drug-eluting stent market has made notable advances to reduce hyperplasia. However, a range of other devices, such as vascular grafts, are still in need of improved protection from cell overgrowth in long-term use.
• The development of a single technology which could simultaneously prevent restenosis and thrombosis would address the multi-functional demands of many vascular devices.
Current Technology Has Limited Ability to Prevent Microbial Growth and Thrombus Accumulation
• Existing antimicrobial and anti-thrombogenic catheters attempt to minimize bacterial colonization and thrombus accumulation by relying on the use of silver, antibiotic, and/or heparin coatings.
‣ Drug-releasing coatings (e.g., silver, heparin) have an inherently limited duration of activity which is ineffective for the chronic (> 90 day) periods of performance demanded by longer term devices such as dialysis catheters.
‣ Both approaches suffer from potential toxicity concerns (e.g., hypersensitivity to antimicrobial agents or potentially fatal heparin allergies), and the use of antibiotic coatings further raises the concern for drug resistance.
‣ These technologies don’t provide a dual-functional surface, which is required to simultaneously prevent the highly interrelated phenomena of biofilm and thrombus formation.
Advice for Patients
When entering a hospital for an extended period of time, patients and their families should refer to the CDC’s LTC (long-term care) Baseline Prevention Practices Assessment Tool 10, a helpful guide to evaluate the status of infection prevention and control efforts in LTC settings.
View the CDC’s LTC Baseline Prevention Practices Assessment Tool.
In addition, patients and their families should always monitor the following:
• The frequency of clinicians’ hand washing.
• The general cleanliness of the hospital room and equipment.
• The cleanliness of visitors who come into contact with the patient.
Prior to their procedure involving an implant, patients are encouraged to consult their clinicians with any concerns they may have regarding device complications. After surgery, patients and their families should keep a watchful eye for symptoms that may develop as a result of device implants, including: 11
• Pain and swelling around an open wound (cut or scrape) of the skin.
• Furuncles (boils) and carbuncles, white-headed pimples around hair follicles.
• Blistering and peeling skin, in infants and young children.
• Swollen lymph nodes in the neck, armpits or groin.
If there is a cause for concern upon making these observations, immediately consult your clinician(s) or other hospital staff to reduce the likelihood of the patient developing an HAI.
Market Solutions in Development
There are a few technological solutions in development being designed to help reduce HAIs, ranging from antimicrobial surfaces to antifouling skins that are designed to inhibit the spread of disease-causing bacteria.
Heparin and silver-based coatings on medical devices have traditionally been effective in limiting the effects of HAIs. Additionally, there are new technologies in development, including non-leaching surfaces that are developed to simultaneously reduce microbial and platelet adhesion and thrombus accumulation.
Beyond the vascular access space, antifouling covers have been effective in modifying surfaces in hospitals such as bed rails, floors, and furniture, to limit the spread of bacteria. Specially-designed industrial steam cleaners have also been useful in disinfecting areas where bacteria are prone to cause problems in healthcare-related settings.