The Global Search for Better Care of Periprosthetic Joint Infection

Periprosthetic joint infection (PJI) has five-year mortality rates between 15% and 25%. That’s higher than the rates for early-stage breast and prostate cancers and similar to the rates for colorectal and blood cancers.

However, these numbers don’t reflect the full burden of PJI, says Cleveland Clinic orthopaedic surgeon Nicolas S. Piuzzi, MD.

“Patients experience loss of strength, confidence and mobility when they have PJI,” he says. “They become fatigued — physically, emotionally and financially — by repeat surgeries. The burden affects medical centers and staff as well. Around the world, we’re seeing the same devastating effects of infection after joint arthroplasty.”

For more than a decade, the orthopaedic surgery community has been exploring new surgical and antibiotic therapies to address PJI, but patient outcomes haven’t improved much.

“There are a lot of unanswered questions, and we keep struggling with how to manage PJI because there aren’t established standards,” Dr. Piuzzi says.

Reviewing PJI around the world

A recent international collaboration of experts has led to a review article, published in The Journal of Bone and Joint Surgery, that captures the current global state of PJI. Rather than serving as a consensus statement, the article presents a snapshot of worldwide trends, challenges and evolving practices in the diagnosis and management of PJI, highlighting similarities and differences across regions.

“We wanted to bring a global perspective to the issue, to understand how physicians and patients around the world face similar challenges, see what we can learn from each other, and collect insights that we can bring back for our patients,” says Dr. Piuzzi, who was lead author of the article.

The article highlighted how:

• Reported rate of PJI varies by country, joint and registry methodology. Diagnostic criteria are applied inconsistently between global regions. A unified definition proposed in 2024, the result of a Delphi consensus project involving various infection and orthopaedic societies, is helping harmonize diagnostic standards.
• All over the world, biofilm-forming microorganisms can make diagnosis difficult.
• Approaches to managing infections — whether DAIR (debridement, antibiotics and implant retention), one-stage, two-stage or 1.5-stage procedures — vary by region. Logistical challenges, available resources and clinical expertise often shape treatment decisions.
• Medical literature lacks consistent definitions of treatment success, making it challenging to compare treatment approaches. Adopting a tiered framework that includes infection eradication, surgical burden, joint function and patient-reported outcomes could help create more standardized and clinically relevant ways to measure and report results.
• New treatment strategies are emerging thanks to progress in immunogenetics, AI risk modeling and precision medicine.

Challenges in standardizing PJI care globally

PJI care is difficult to standardize because PJI is complicated, says article coauthor Anabelle Visperas, PhD, one of the leading PJI scientists at Cleveland Clinic and a researcher specializing in immunology and orthopaedics.

“One major problem is that we don’t understand infection very well,” she says. “A major, often unrecognized component is the host, the patient. Each patient is different, and even if you know the pathogens involved in their infection, you still don’t know how their body will react.”

Defense mechanisms are highly personalized, she says. To better understand treatments, researchers need to better understand how individual bodies fight infections.

In addition, surgical and antibiotic strategies vary globally because the strains of bacteria are different in different regions.

Looking ahead

Dr. Visperas predicts that advances in understanding host immune response will be a big development in PJI care over the next decade. Dr. Piuzzi agrees and adds that the ability to modulate biology in different ways and personalize treatment also will change PJI care.

“Treatments will challenge convention and come from outside our current tool kit,” he predicts. “There are some novel therapies that we’re testing now that may prove to be effective in certain settings. However, testing the efficacy and safety of these therapies is hard because the cohorts of patients with PJI are so small.”

Progress requires global collaboration

Progress in improving PJI care requires multidisciplinary and likely global collaboration, say the researchers.

“We are not going to achieve this in isolation,” Dr. Piuzzi says. “This isn’t a fight we can win only in infectious disease or orthopaedics or research. We need to get out of our comfort areas and interact with cross-specialty teams to find answers collectively.”

That approach has driven advances in oncology, he notes. The same level of multidisciplinary care is required for PJI.

“Our review article is a call to action for medical institutions, funding agencies and philanthropic groups that are willing to collaborate to solve the PJI problem and provide an environment of meaningful change for patients,” Dr. Piuzzi concludes. “PJI isn’t just a complication of joint surgery, it’s a chronic, life-changing disease. It’s up to us to restore hope and quality of life for our patients.”