A proof of concept study on the knee joints of mice, conducted by Johns Hopkins University researchers shows that a coating made with antibiotic-releasing nano fibers can prevent serious bacterial infections related to joint replacement surgery.
The technology, the researchers say, would have “broad applicability” in the use of orthopedic prostheses, such as hip and knee total joint replacements, as well pacemakers, stents and other implantable medical devices. In contrast to other coatings in development, the new material can release multiple antibiotics in a strategically timed way for an optimal effect.
“We can potentially coat any metallic implant that we put into patients, from prosthetic joints, rods, screws and plates to pacemakers, implantable defibrillators and dental hardware, ” said co-senior study author Lloyd S. Miller, M.D., Ph.D., an associate professor of dermatology and orthopedic surgery.
Every year in the U.S., an estimated 1% to 2% of the more than 1 million hip and knee replacement surgeries are followed by infections linked to the formation of biofilms—layers of bacteria that adhere to a surface, forming a dense, impenetrable matrix of proteins, sugars and DNA. Immediately after surgery, an acute infection causes swelling and redness that can often be treated with intravenous antibiotics.
In some people, low-grade chronic infections can last for months, causing bone loss that leads to implant loosening and ultimately failure of the new prosthesis. These infections are very difficult to treat and, in many cases of chronic infection, prostheses must be removed and patients placed on long courses of antibiotics before a new prosthesis can be implanted. The cost per patient often exceeds $100, 000 to treat a biofilm-associated prosthesis infection, Miller says.
Surgeons and biomedical engineers have for years looked for better ways—including antibiotic coatings—to reduce these risks of infections that are a known complication of implanting artificial hip, knee and shoulder joints.
In contrast to other coatings in development, the new material can release multiple antibiotics in a strategically timed way for an optimal effect.
“We can potentially coat any metallic implant that we put into patients, from prosthetic joints, rods, screws and plates to pacemakers, implantable defibrillators and dental hardware, ” says Miller,
To test the technology’s ability to prevent infection, the researchers loaded the nanofiber coating with the antibiotic rifampin in combination with one of three other antibiotics: vancomycin, daptomycin or linezolid. “Rifampin has excellent anti-biofilm activity but cannot be used alone because bacteria would rapidly develop resistance, ” says Miller. The coatings released vancomycin, daptomycin or linezolid for seven to 14 days and rifampin over three to five days. “We were able to deploy two antibiotics against potential infection while ensuring rifampin was never present as a single agent.”.
The team then used each combination to coat titanium Kirschner wires—a type of pin used in orthopedic surgery to fix bone in place after wrist fractures. They inserted them into the knee joints of anesthetized mice and introduced a strain of Staphylococcus aureus, a bacterium that commonly causes biofilm-associated infections in orthopedic surgeries.
Miller says that after 14 days of infection in mice that received an antibiotic-free coating on the pins, all of the mice had abundant bacteria in the infected tissue around the knee joint, and 80% had bacteria on the surface of the implant. In contrast, after the same time period in mice that received pins with either linezolid-rifampin or daptomycin-rifampin coating, none of the mice had detectable bacteria either on the implants or in the surrounding tissue.
According to Dr. Miller, “We were able to completely eradicate infection with this coating. Most other approaches only decrease the number of bacteria but don’t generally or reliably prevent infections.”
After the two-week test, each of the rodents’ joints and adjacent bones were removed for further study. Miller and Hai-Quan Mao, Ph.D. found that not only had infection been prevented, but the bone loss often seen near infected joints—which creates the prosthetic loosening in patients—had also been completely avoided in animals that received pins with the antibiotic-loaded coating.
