Infection Control Strategies Offer a Plan of Pathogen Attack

Hospital-acquired infections—or healthcare-associated infections—are acquired infections that aren’t present or incubating at the patient’s time of admission into the hospital. They can include catheter-associated urinary tract infections, central line-associated bloodstream infections, surgical site infections, ventilator-associated pneumonia, hospital-acquired pneumonia, and Clostridium difficile infections, among others. The infections are usually acquired after hospitalization and manifest 48 hours after admission to the hospital.¹ Hospitals have been taking hospital-acquired infections seriously for the last few decades. Many hospitals have put infection tracking and surveillance systems in place and built prevention strategies to reduce the rate of infections.

The impact isn’t just seen at the level of individual patients—they affect the community because the infections have been linked to multi drug-resistant infections. The risk for hospital-acquired infections depends largely on the facility’s infection control practices, but is also affected by the patient’s immune status and prevalence of various pathogens within the community. Specific patient-related risk factors include immunosuppression, older age, length of stay in the hospital, underlying comorbidities, frequent visits to clinics, mechanical ventilatory support, indwelling catheters, stay in an intensive care unit, and recent invasive procedures like orthopedic surgery.

“Infection control is a major concern in orthopedic surgery because of the possibility of contamination from blood and other bodily fluids,” said Arjun Luthra, commercial director of BioInteractions, a U.K.-based research and development company specializing in biocompatible material technologies for the medical device industry. “Even with many precautions and protocols to prevent infection, any surgery that requires an incision increases the chance of surgical site infections due to the germs normally found on the skin. Similarly, orthopedic-device related infections are one of the most challenging complications for patients after orthopedic surgery. Comparable to healthcare-associated infections (HAIs), these infections are a significant burden on our healthcare systems both in the U.K. and across the world, and require special prevention strategies.”

Introduction of an implant into the body comes with the risk of microbial infection, particularly for fixing open-fractured bones and joint revision surgeries. Infection can lead to implant failure, and one of the most worrisome complications of spinal surgery continues to be post-operative spinal implant infection (PSII). Depending on the virulence of the microbes, PSII can either manifest early on (within four weeks of surgery) or be delayed more than four weeks after surgery.²

It can be challenging to treat orthopedic implant infections that may lead to replacement of the implant or, in extreme cases, amputation and mortality. Sources of the infection bacteria come from various areas, including the operating room environment, surgical equipment, clothes worn by medical staff, resident bacteria on the patient’s skin, and bacteria already present inside the patient’s body.

“In addition, medical implants can lead to severe infections in the patient and present a major problem in orthopedic surgery, which can often lead to implant failure,” said Luthra. “These infections are normally the result of bacterial adhesion to an implant surface and resulting biofilm formation on the implant surface. Therefore, inhibiting bacterial adhesion is essential to prevent implant-associated infection because the biofilm is progressively becoming extremely resistant to antibiotics used to treat infections. New intervention strategies to either prevent or treat orthopedic implant-related infections are the future. Various technologies to be adopted to prevent implant infection are still evolving and strategies to develop the best bioengineering method to bond the antimicrobial coating securely to the material of different medical devices, for their lifecycle, are coming to light in the medical device industry.”

This article will cover several infection control strategies certain medical device makers and suppliers are taking to combat hospital-acquired infections for orthopedic surgeries and related fields.

TridAnt Antimicrobial

BioInteractions develops advanced and specialized coatings for devices that are used in medical treatments and procedures ranging from Class I to Class III implants. The company has been a supplier to the medical device industry for over 30 years. Its portfolio of multi-action materials addresses chronic challenges like thrombus (clot) formation, infections, complication at the interface of the device and tissue, and other biocompatibility challenges. The company has licensing contracts with major medical device manufacturers around the world.

Its TridAnt antimicrobial coating tackles the problem of HAIs in clinical settings.

“We understand the broad impact [hospital-acquired infections] have and have developed a technology platform in TridAnt to tackle these from a preventative standpoint,” said Luthra. “Antibiotics, vaccines, and other drugs help to treat [AL1] infections but are becoming limited in their overall impact. What is needed in the future is an antimicrobial solution that works alongside other measures to prevent a wide range of infections and protects patients for the long-term.”

TridAnt is a non-leaching coating that endows a surface with infection resistance and minimizes formation of biofilms. The coating targets a wide variety of bacteria to significantly reduce the chances of infections. According to the company, the coated surface interacts with bacteria and causes them to physically lyse (disintegrate due to rupture in the cell wall or membrane). The process is non-leaching and offers a consistent effect without degradation of impact by the releasing components.

“Our TridAnt enhanced antimicrobial coating solution offers a new way to combat infections more effectively, efficiently, and for longer,” said Luthra. “Based on over three decades of dedicated research and trials, TridAnt is fully compliant with current medical device regulations, has been independently tested to international standards (ISO, EN, PAS), and was proven to provide monoclonal protection, which kills a broad spectrum of pathogens including gram-positive, gram-negative, and drug resistant bacteria, as well as enveloped and non-enveloped viruses and yeast. These include E.Coli, MRSA, Influenza, Norovirus, and SARS-CoV-2.”

According to the company, the coating protects against infection from the moment the device is deployed. It can protect the medical device consistently for up to 365 days. Using both active and passive agents gives the coating the ability to eliminate bacteria, prevent formation of biofilm, and inhibit bacteria from adhering to the surface of the device.

Clinical applications include central venous devices, endotracheal tubes, intraocular lenses, titanium cranioplasty, and neurological stents.

“The new biocompatible antimicrobial technology includes active components that target microbes (prokaryotic cells) and is non-leaching, which has a reduced risk to human cells unlike previous technologies,” said Luthra. “It is the first known medical device technology to kill a wide range of pathogens in under 15 seconds, prevents the formation of biofilms for up to 365 days (and is safe enough to protect skin for up to 48 hours), with non-leaching technology to provide a constant level of protection over long periods of time.”

Biomimetic Surface Technology

Pasadena, Calif.-based ACatechol provides technologies for surfaces that prevent nosocomial (originating in a hospital) infections and promote/prevent adhesion of objects and microbes. The company’s underwater bonding and on-demand debonding technologies are currently undergoing commercialization in a partnership with Envista Holdings and a product launch is expected in Q4 2023. The technology tackles long-standing problems with current orthodontic adhesives that can irreversibly damage healthy enamel surfaces.

“ACatechol is a startup medtech company providing novel surface technologies. ACatechol Inc. (Delaware C. Corp) was founded in 2016 by four partners—Kollbe Ahn (ex-professor/faculty of UCF and UC Santa Barbara), Eric Ryan, Phillip Ho, and Jinsoo Ahn,” said Kollbe Ahn, Ph.D., CEO of ACatechol. “Since then, ACatechol has developed several surface treatment technologies, resulting in three granted and two pending patent families, which were subsequently licensed out to Danaher in 2018 to be applied to their dental devices. ACatechol’s non-invasive surface bonding and on-demand debonding technology address long-standing issues with existing orthodontic treatments that irreversibly damage healthy native tissues.”

Greater than half of deaths from COVID-19 can be attributed to acute respiratory distress syndrome (ARDS) due to secondary healthcare-acquired infections like ventilator-associated pneumonia (VAP). Devices like indwelling catheters (endotracheal tubes) that are used for ventilation processes don’t have mechanisms to prevent bacterial colonization on their surfaces.

“In 2020, ACatechol recognized the importance of surface treatments/modifications, as infections are transmitted through contacts,” said Dr. Ahn. “Funded by an NSF COVID-19 research grant, we developed a new self-sanitizing surface technology showing superior efficacy and durability over current products, and we are now in the process of scaling up the production of a durable self-sanitizing coating.”

“One of the potential applications of the antimicrobial surface technology is indwelling medical devices such as catheters,” Dr. Ahn continued. “Over 3 million central lines (central venous catheters or CVCs) are inserted into patients in the U.S. annually, resulting in over 250,000 central line-associated bloodstream infections (CLABSIs), of which over 100,000 occur in patients receiving hemodialysis therapy for kidney disease. These infections are lethal and expensive—mortality rates are estimated at 14% to 40%, and cost U.S. healthcare providers in excess of $12.5 billion (250,000 cases x $50,000 per case) annually without reimbursement (as Medicare & Medicaid programs do not reimburse costs to treat CLABSIs).”

The company developed a new class of antifouling coatings by using a surface modification technique called silanization with powerful gemini-surfactant technology. According to the company, in pilot studies the technique showed high levels of hydrophilicity and resistance to bacterial colonization.

“One of the tools currently used to reduce CLABSIs is use of CVCs with antimicrobial features,” said Dr. Ahn. “Despite antimicrobial properties, such catheters remain susceptible to biofouling/biofilm formation as their surface properties do not display repellency to biofoulants and cellular debris from dead bacteria, thereby remaining susceptible to the formation and adherence of infectious biofilms. Funded by NIH NIAID, ACatechol has recently developed anti-infective (antibiofilm and antimicrobial) CVC, leveraging the success of surface-modification technology, developed with an NSF COVID-19 research grant.”

The technology has the potential to give catheters unmatched antifouling properties, and could clinically reduce the incidence of secondary infections in intubated patients to prevent ARDS—reducing overall COVID-19 mortality.

“ACatechol’s technology incorporates biofilm-repellent moieties together with antimicrobial moieties into CVC surfaces,” said Dr. Ahn. “In this strategy, the biofouling residues serve to continuously repel biofoulants, while antimicrobials kill any microorganisms not sufficiently repelled on contact. The study confirmed the synergetic effect of the biofilm-repellent and antimicrobial strategies. ACatechol is now producing prototype CVCs with superior anti-infective and anti-thrombotic properties, compared to current CVCs. ACatechol’s anti-infective CVCs show resistance to biofilm formation longer than six to 12 months. This technology will significantly reduce CLABSIs, resulting in saving lives and associated pains and costs.”

The technology, according to the company, can also be used in intravenous, urinary, central venous, and hemodialysis catheters, which together address an estimated market size of $77.7 billion by 2026.

“If we successfully demonstrate >20% reduction of infection rate in the following in-vivo and clinical studies as shown in the in-vitro study (>20% reductions in biofilm, proliferation, and antimicrobial assays with improved hemocompatibility compared to current CVCs), the expected outcome is significant, because over 20% reduction in the national infection rate would prevent more than 50,000 CLABSI cases, saving over 10,000 lives and over $2.5 billion in direct healthcare costs each year in the U.S. alone,” said Dr. Ahn.

Investing Against Infection

Swedish medical device maker Getinge touts a broad portfolio of products, solutions, and services in the hospital and life sciences markets. These include cardiac, pulmonary, and vascular therapies, intensive care products, as well as products and solutions for surgical workflows and hospital infrastructure. Included in its arsenal are technologies for both decontamination and sterilization.

Getinge’s portfolio of washers address applications like cGMP cleaning in biopharmaceutical production to the research space. Its lab washers offer clean and contamination-free glass and labware for a variety of laboratory settings. The company also offers sterilizers for components, equipment, and tubs as well as terminal sterilization. Some sterilization systems address the need for reprocessing of cages and racks, and dedicated lab sterilizers offer reliable processes for a variety of applications and lab requirements.

“Sterile processing departments across North America are facing a variety of mounting pressures in the post-COVID healthcare environment,” said Don McAllister, VP Infection Control Sales, U.S., for Getinge. “Some of the most prominent challenges include staffing shortages, increased throughput demand as elective surgeries return to a pre-pandemic pace, and an increased complexity in instrumentation (including those used in robotic surgeries) that needs sterilization.”

This past March, Getinge acquired Ultra Clean Systems Inc. in a SEK 170 million ($16 million) deal. Getinge has been the exclusive distributor of Ultra Clean’s North American offering for nearly a decade. The company is a U.S. manufacturer of ultrasonic cleaning technologies that are used in hospitals and surgery centers to decontaminate surgical instruments. Ultrasonic cleaning is a critical part of best practices to reprocess instruments—particularly the most complex ones used in surgical robotics—in order to reduce the risk of hospital-acquired infections.

“The acquisition of Ultra Clean Systems demonstrates Getinge’s commitment to continuous innovation in sterile processing,” said Patty Fitch, president, North America for Getinge. “Our partnership with Ultra Clean dates back almost a decade and aligns perfectly with our vision to provide complete sterilization solutions to our customers—from sterile processing capital equipment to consumables to tracking software. Ultrasonic cleaning systems are an integral part of our comprehensive portfolio and are particularly useful in cleaning the complex instruments used in robotic surgery. Additionally, Ultra Clean is one of the most recognized and trusted brands for ultrasonic cleaning in the industry. Getinge’s long-standing relationship with this supplier made it a natural strategic fit as a fold-in acquisition.”

Getinge will add Ultra Clean’s titanium rod transducer (TRT) technology to its portfolio to offer customers higher standard ultrasonic medical instrument cleaning. According to Ultra Clean, TRT technology creates a high cavitation energy output—79 watts per gallon with a frequency of 40 kHz—with a rod that sits in the basin instead of below it. This offers uniform energy distribution and eliminates cold spots. The technology is ideal to clean complex instruments used in laparoscopic, orthopedic, ophthalmic, and robotic surgical procedures.

“The acquisition of Ultra Clean allows us to continue to seamlessly integrate ultrasonic solutions into departments across North America,” said McAllister. “Ultra Clean offers the largest portfolio range on the market with tabletop and floor models to match the unique needs of virtually any medical facility.”

With eight- to 13-minute adjustable cleaning cycles, TRT technology can reduce cleaning times compared to bonded transducers. Many ultrasonic cleaning systems pass their energy from surface-mounted transducers, via a bonding agent, through the metal basin, and into the water. This causes a power loss of about 20%.

According to the company, the technology offers 15-minute cleaning cycles for da Vinci robotic instruments and provides a longer life for both cleaning equipment and instruments cleaned. There’s less maintenance involved, reducing machine downtime and associated costs. More thorough cleaning in one cycle also allows customers to keep instrument sets together.

Changing the Face of Titanium

Titanium and its alloys are critical for orthopedic and dental procedures, but they still require using surface modification technologies to achieve robust osseointegration and increase antibacterial properties to avoid implant-associated infections. These technologies include plasma spray, plasma immersion ion implantation, plasma immersion ion implantation and deposition, physical vapor deposition, chemical vapor deposition, sol-gel, and micro-arc oxidation methods.

Kinamed, based in Camarillo, Calif., is a designer and manufacturer of implantables and instruments for the orthopedics, cardiothoracic, and neurosurgery specialties. William Pratt, vice president of operations and director of creative design for Kinamed Inc., spoke to ODT about a titanium surface modification technology to change hydrophilicity that he has been working on for a few years.

“The titanium surface modification technology would be used for probably any implantable that’s compatible with the process—which in our experience, involves anodizing in the presence of hydrofluoric acid and subsequent heat treating,” said Pratt.

Titanium anodizing is an electrolytic finishing process that manipulates the oxide layer on the titanium’s surface using an electric current. The medical device industry widely uses titanium anodizing processing because anodized titanium parts are nontoxic and suitable for orthopedic implants.

Pratt explained how the titanium surface modification technology works to improve infection control of orthopedic devices.

“There is a deep body of research in this area, but in general, it’s about the race to the surface,” said Pratt. “If we can hold off the colonization of the surface by the bad organisms long enough for the body to occupy the surface with its own proteins and subsequent cellular coverage, it’s a win. High hydrophilicity is antagonistic to the biofilm formation of organisms that are most feared in the operative environment.”

The choice of a particular surface topography remains a debated topic among healthcare practitioners. Increased surface level hydrophilicity has been shown to boost osseointegration and shorten healing times—in addition to, of course, providing extra protection against microorganisms.

“From a design perspective and in my experience, other forms of anodization like colorizing are incompatible—the nano surface modification takes precedence,” said Pratt. “Also, this is the world of the extremely small, well beyond the sensitivity of any optical microscopy. All surfaces have features at the nano level; it comes down to the character of those features that influence the interaction of the surface with its environment. The beauty and simplicity of titanium surface modification is we’re working with the parent material–it’s a structured oxide layer instead of a random topology—and it still has the natural durability and compatibility of titanium oxide.” 

References

1. bit.ly/mpo05231
2. bit.ly/mpo05232