Joint Infection Mortality After Knee Replacement Surpasses Common Cancers

The rate of periprosthetic joint infection (PJI) after knee replacement in the U.S. is 2% or less — very rare. However, thanks to the growing prevalence of total knee arthroplasty (TKA) procedures, the number of patients with PJI is substantial, tens of thousands each year, estimates Nicolas S. Piuzzi, MD, Enterprise Vice Chair of Research for Orthopaedics and Rehabilitation at Cleveland Clinic.

“Despite the advancements we’ve made in TKA, we’ve not been able to improve our ability to clear infections,” he says. “PJI is extremely difficult to treat. It requires many resources. It takes a toll on patients, many who require more surgery or need intravenous antibiotics. Mortality due to PJI is not uncommon.”

To raise more awareness of the gravity of PJI after knee replacement, the Cleveland Clinic Adult Reconstruction Research (CCARR) group, led by Dr. Piuzzi, conducted a meta-analysis of published data on the topic.

“Ours is the largest study to date exploring the status of PJI after knee arthroplasty in the U.S. and the first to report mortality after standard PJI treatments,” Dr. Piuzzi says. “It has been a tremendous undertaking by one of our Cleveland Clinic Lerner College of Medicine students, Michael Ramos, who is spending one year with our research group.”

Ramos will present data from the study at the 2025 American Academy of Orthopaedic Surgeons meeting.

Mortality varies by PJI treatment

The CCARR team searched national databases for articles on knee arthroplasty, joint infection and mortality. They found 29 studies that fit their criteria (i.e., full-length, original articles; excluding oncologic, infectious or traumatic indications for TKA; involving no more than 5% of patients treated with amputation or resection arthroplasty), comprising nearly 80,000 patients (mean age 67).

With a mean follow-up of 4.1 years (range: 1 month – 17 years), overall mortality was 11.6% (95% CI: 6.8-17.5).

Mortality varied by treatment (P < .0001):

• Debridement, antibiotics and implant retention (DAIR): 7.3% mortality (95% CI: 1.2-17.1)
• One-stage exchange: 0.6% mortality (95% CI: 0-3.4)
• Two-stage exchange: 11.5% mortality (95% CI: 8.0-15.5)

In a subgroup analysis comparing DAIR with two-stage exchange, no differences in mortality were observed at 3 or 12 months.

Mortality compared to common cancers

“In this study, mortality after TKA PJI was 11.6% at 4.1 years,” says Ramos. “That’s higher than the five-year mortality rates for some common cancers.”

Compared to five-year mortality rates published in 2021 by the American Cancer Society, rates of PJI after TKA are:

• 5.8 times higher than prostate cancer (2%)
• About 1.7 times higher than melanoma (7%)
• About the same as breast cancer (10%)

A call to action

“This study is really a call to action for policymakers and the entire medical community,” Dr. Piuzzi says. “We need more resources to take care of PJI patients the way we take care of cancer patients. For cancer patients, we assemble multidisciplinary teams and have reimbursement that matches the higher level of care required. Currently, we don’t have that for PJI patients.”

PJI is a life-threatening condition that requires intensive, multidisciplinary management, he emphasizes.

Cleveland Clinic is continuing to study why PJIs occur. Dr. Piuzzi and CCARR investigator Anabelle Visperas, PhD, are leading a team of Cleveland Clinic orthopaedic, immunology, microbiology and infectious disease experts to explore the multitude of factors that affect PJI.

“We are trying to see if we can optimize the host and find another way to address PJI treatment and prevention,” Dr. Piuzzi says.