New Therapeutic Approaches to Periprosthetic Knee Infections

    In this report from the EFORT Congress, surgeons from Europe urge their colleagues to consider alternatives to 2-stage revision for certain infections after total knee replacement.

    Periprosthetic infections are among the most serious complications in the field of endoprosthetics. They not only mean potentially devastating emotional and financial tolls for patients, but they are also associated with high costs for public health systems.

    “In the United Kingdom the total burden caused by infections has risen by 92% over the past 5 years and will continue to increase exponentially,” said William Jackson, BSc, MBBS, FRCS(Orth), from the Oxford University Hospitals NHS Trust, at the 16th EFORT Congress in Prague, Czech Republic.

    “Treating infections in total knee replacements (TKR) can cost up to 70,000 pounds in each case, exposing the British healthcare system to costs of around 160 million pounds or 220 million euros each year.”

    According to Dr. Jackson, infection following TKR procedures is a growing problem. He attributes this to a combination of factors, including:

    • The increasing number of knee replacement surgeries performed annually
    • An increasing rate of obesity in the general population
    • Higher life expectancy
    • Steady decline in the age of patients receiving treatment

    DAIR and Antibiotic Cement as Treatment Options

    If an element of the knee endoprosthesis is infected, in many cases the only certain way to entirely eradicate the infection is to completely remove all of the prosthetic material. This usually calls for a 2-stage revision operation that “comes at huge cost both financially and often with functional limitations for the patient,” Dr. Jackson said.

    For several years, knee specialists in Oxford have taken a different approach, with the aim of preserving the prosthetic components to the fullest possible extent.

    “This approach allowed us to achieve new levels of infection control – an 80% survival rate of components after 8 years – and the functional outcome is akin to that of a complication-free joint replacement surgery.”

    He is urging orthopaedic surgeons to consider surgical debridement, antibiotics, and implant retention (DAIR) as a potential treatment option, even when the infection is chronic, in situations in which the implant is well fixed and functional.

    A recent study from the U.S. that was presented at the EFORT meeting, demonstrated that adding antibiotics to the bone cement is an efficient way of combating periprosthetic infection. According to the study’s findings, antibiotic bone cement reduces the re-revision risk in knee endoprosthetics by around 45%.

    Advantages of 2-stage Revision Not as Clear-Cut as Previously Thought

    The latest chapter in the debate over the relative merits of 1- versus 2-stage revision operations – presented at this year’s EFORT Congress – casts fresh doubt on the 2-stage surgical approach’s reputation as the gold standard.

    “The difference in infection rates between 1-stage and 2-stage procedures is lower than previously thought,” said Prof. Carlo Romanò, Immediate Past-President of the European Bone & Joint Infection Society (EBJIS) and Professor of Orthopaedics at the University of Milan.

    “As recently as 3 years ago, we still believed that protection from infection was around 10% higher with a 2-stage approach.”

    But a new review, containing the results of studies completed up to March 2015 and authored by a group of knee reconstruction surgery experts headed by Prof. Romanó and Prof. Fares Haddad from London, showed that the actual difference is just 4%.

    Single-stage Revision Can Cut Costs

    These results do more than raise the status of single-stage revision as an option for knee surgery. “This approach reduces the amount of time spent in hospital and reduces the financial burden on the healthcare system, Prof. Romanò said.

    “What’s more, the availability of antibacterial coatings such as DAC (defensive antibacterial coating) hydrogel support the use of cement-free implants in single-stage revision, meaning that implants can be removed more easily in the event of malfunction than long-stem cemented revision implants, which had until now been required for single-stage revisions.”

    However, preference should still be given 2-stage revisions in certain circumstances. “This approach may still be preferable when the pathogen is unknown or in particularly long lasting and diffuse infections, since a double procedure may be better suited for removal of all infected tissue,” Prof. Romanó said.

    Infection the Main Cause of Knee Endoprosthetis Issues 

    Periprosthetic knee infections occur in approximately 2% of endoprosthetics patients. “These are among the main cause of complications in knee endoprosthetics. In high-risk patients, particularly those with diabetes, renal impairment or peripheral vasculopathy, the incidence of complications is considerably higher and increases once again when multiple risk factors converge,” Prof Romanó said.

    It should be noted that, “a significant proportion of aseptic loosening of implants is attributable to low-grade infections, difficult to diagnose and caused by slow-growing microorganisms,” he added.

    “In light of this, it is essential that all medical facilities involved in revision surgery put high microbiological laboratory standards in place and subject implants to precise microbiological analysis after removal.”

    Highly Effective New Antibacterial-loaded Coatings

    In terms of preventing periprosthetic knee infections, specialists have high hopes for new antibacterial coatings. 

    “These can cut bacterial growth on the implant by more than 90%,” said Prof Romanó. “The rapidly resorbing hydrogel DAC has been available in Europe for more than a year, which is designed to be intraoperatively loaded with antibiotics and to be applied on the surface of any cementless joint prosthesis or osteosynthesis material.

    “Use of hydrogels has been approved as safe and does not lead to impairment of implant osseointegration. In-vivo studies demonstrate its effectiveness in reducing implant-related infection even in animal models with high bacterial contamination.”

    Diagnostic advances are also to be expected: Use of biomarkers in joint fluids in tandem with esterases and monitoring of leucocytes could lead to highly accurate diagnosis of periprosthetic knee infections.

    “Moreover, new antibiofilm agents, used to rid implants of bacteria, have the potential to completely change our sampling activities and procedures surrounding non-functional prostheses,” Prof. Romanó said. “This technology is at the heart of microDTTect, a new medical device based on an antibiofilm compound – dithiothreitol, DTT – which will soon be available in Europe.”

    Calls for Pan-European Certification Process

    Periprothetic infections also pose a serious problem from a socio-economic perspective.

    “We estimate that the direct costs for orthopaedic surgery alone in Europe total some EUR 2 billion. The indirect costs and medical and legal effects are hard to quantify, but you have to start at somewhere around double that figure,” Prof Romanó said.

    One of the key priorities of the EBJIS Board is to bring about the introduction of a pan-European certification process for medical facilities that focus on treating periprosthetic infections, with EFORT’s support.

    “Since surgical treatment of periprothetic infections is highly complex and quite expensive, it calls for specially trained medical experts and dedicated facilities,” Prof Romanó said. “At the moment there is no European standard in place, and operations are often conducted by surgeons who only encounter 1 or 2 such cases each year. This raises the risk of incorrect diagnosis and treatment, which in turn leads to the additional costs associated with managing complications.”