Tackling The Achilles Heel of Joint Arthroplasty: Periprosthetic Joint Infections
September 25, 2024
Periprosthetic joint infections (PJIs) are a significant challenge in orthopaedic surgery, particularly given the increasing number of hip and knee replacements performed annually in the United States. These infections can lead to painful complications, complex treatments, and often, the need for revision surgeries.
F. Johannes Plate, MD, PhD, an orthopaedic surgeon in the Department of Orthopaedic Surgery at the University of Pittsburgh and director of Adult Reconstruction Research, along with colleagues from the Department, has been actively involved in research to improve the treatment of PJIs, notably contributing to the Apex-2 clinical trial (A Second Trial of the Abbreviated Protocol Two Stage Exchange) exploring novel devices and alternative strategies for managing these difficult-to-treat infections and revision hip or knee arthroplasties.
“While advances in prosthetic materials and surgical techniques have reduced the majority of complications related to total joint replacements, PJIs remain a persistent issue facing the arthroplasty field,” says Dr. Plate.
The Problem of Periprosthetic Joint Infections
In the U.S., the number of total hip and knee replacements continues to rise, with hundreds of thousands of these surgeries performed each year.
The literature points to anywhere from 1% to 5% of patients undergoing joint replacement surgery will develop a PJI, either shortly after surgery (early PJI) or years later (late PJI).
"Periprosthetic joint infections are one of the leading causes of revision surgeries in total hip and knee arthroplasties," says Dr. Plate. "Infections can arise from an issue with the incision after surgery or from bacteria entering the bloodstream and reaching the joint years later. These cases can be extremely challenging to treat."
Late infections, occurring years after the initial surgery can be problematic. Often, the source of infection, causative bacteria, or the timing of the infection are unknown. If the infection has persisted for too long causing inflammation, pain, and swelling in the joint, the implants may need to be removed in surgery and a later time replaced through yet another revision procedure once, and if, the infection is cleared.
“PJIs are notoriously difficult to manage with antibiotics alone because the bacteria invading the joint form nearly impenetrable biofilms on the metal surfaces of prosthetic joints,” says Dr. Plate. “These biofilms make the infection highly resistant to conventional treatment approaches without removing the implants.”
Treatment Challenges and Current Approaches
Treating PJIs typically requires surgical intervention. In early infections, surgeons may remove infected tissue, clean the joint, and replace some of the modular prosthetic components in an effort to mitigate the infection. However, chronic infections — where bacteria have adhered to the metal surfaces — often necessitate the complete removal of the prosthesis, and, in the best of all possible worlds, replacement with a new device.
“In the U.S., the standard approach for chronic infections is a two-stage revision surgery,” says Dr. Plate. “First, we remove the infected implant and insert an antibiotic spacer. The patient then receives intravenous antibiotics for a period of time, often a minimum of six weeks, followed by another surgery to implant a new prosthesis after the infection has been confirmed cleared – and if the patient still remains a good candidate for surgery, which sometimes is not the case. This process can take several months leaving the patient with limited mobility and a long recovery.”
Patients with chronic PJIs face additional surgical challenges. Reimplantation surgeries are often more complex due to bone loss, the presence of scar tissue, or compromised ligaments necessitating specialized components with metal augmentation or linked components to make up for nonfunctional ligaments.
"Revision surgeries are never routine. They are difficult because you're often working with patients who haven't had a functional joint for some time," says Dr. Plate. "Reconstructing the joint can be challenging, requiring specialized surgical skills and techniques not available at every facility that conducts hip and knee replacements. Oftentimes patients are referred to us and travel long distances to our Joint Replacement Center to receive the care required for these challenging problems."
A New Approach: The Apex Clinical Trials
Recognizing the need for more efficient and efficacious treatment protocols for PJI and revision surgeries, Dr. Plate and UPMC Orthopaedic Care were one of the main centers enrolling patients in the Apex-2 (A Second Trial of the Abbreviated Protocol for Two-Stage Exchange) clinical trial, sponsored by Osteal Therapeutics®. This trial, along with the initial Apex trial explored the efficacy of a shortened treatment pathway for PJIs. This new approach was designed to provide patients with a shorter time interval between implant removal and reimplantation of a new hip or knee replacement for chronic PJI with the potential for faster recovery without compromising clinical outcomes.
“The Apex trials studied an abbreviated two-stage exchange protocol,” says Dr. Plate. “Instead of waiting several months, patients underwent removal of the infected implants and then received continuous infusions of antibiotics (vancomycin and tobramycin) directly into the joint for seven days with the Osteal Therapeutics VT-X7® system while in the hospital. After this abbreviated course of antibiotic treatment, patients underwent reimplantation with a new prosthesis followed by immediate physical therapy and rehabilitation.”
The Apex trials have produced promising results. Patients treated with the abbreviated protocol had their reimplantation after only seven days, compared to the traditional timeframe of approximately three months. Moreover, 100% of the patients in the Apex-2 trial enrolled in the abbreviated protocol arm underwent successful reimplantation, while only 75% of those treated with a standard two-stage exchange received a new prosthesis.
“Reducing the time between procedures improves overall function and quality of life for these patients,” says Dr. Plate. “It offers a faster, more effective way to manage PJIs, and it could become a new standard of care that we use for well-selected patients in the future.”
Prehabilitation and Patient Optimization
In addition to managing infections in cases of joint arthroplasty, Dr. Plate emphasizes the continuing importance of patient optimization before elective surgeries. For joint replacements, this includes controlling conditions such as diabetes, managing weight, and improving muscle strength through physical therapy.
“For elective joint surgeries, we focus on preoptimization and prehabilitation — ensuring the patient is in the best possible health before surgery,” says Dr. Plate. “This can significantly decrease the risk of complications and improve joint replacement outcomes so that patients may only need one surgery that gets them back to normal life without joint pain.”
However, for patients with PJIs, there is often little time for presurgical optimization. Many of these patients present with underlying conditions, such as obesity or poorly controlled diabetes, which contribute to their increased risk of infection.
"In these cases, it's difficult to fully optimize the patient before surgery, but we do our best to improve their condition before reimplantation,” says Dr. Plate. “We have standardized protocols in place for all of our joint replacement patients that focus on nutrition, physical activity, and other health factors to enhance their recovery prospects.”
A Push for Centers of Excellence in PJI Treatment
Because the ongoing battle with PJI is likely to continue, Dr. Plate indicates that there is need for specialized centers to manage PJIs, and that there is a push nationally to create just such a referral network to optimize care for these cases.
“There’s a growing national discussion about establishing regional centers of excellence, specifically for joint infections,” says Dr. Plate. “At UPMC, with our expertise, infrastructure, and forward-looking approach to orthopaedic and musculoskeletal care, we are looking to become one of these centers in western Pennsylvania.”
These centers would focus on treating PJIs with a high level of expertise, providing the latest treatments, including those explored in the Apex trials. Such a model would consolidate the care of complex joint infections, ensuring that patients receive comprehensive, specialized treatment with the best possible chance for optimal long-term clinical outcomes and quality of life.
The Path Forward
With ongoing research and innovations like the Apex trial and other research Dr. Plate and colleagues are currently conducting at UPMC Orthopaedic Care, the treatment landscape for PJIs is evolving. By focusing on faster, more effective treatments and emphasizing patient optimization, limiting the toll that PJIs inflict on the field of joint arthroplasty may be in reach.
“Periprosthetic joint infections remain a significant challenge, but through research, collaboration, and specialized care, we are making real progress,” says Dr. Plate. “Studies like the Apex trial and much of the work our group has been and is continuing to do over many years shows that we can reduce recovery times and improve outcomes, and we’re excited to see where this research and clinical practice takes us to help our patients with these challenging problems.”
References and Further Reading
