October 07, 2026
8 min read
Key takeaways:
- Infection remains one of the most difficult, unresolved complications associated with joint replacement.
- Despite low incidence rates, the 5-year survival rate of PJI is comparable to or worse than some cancers.
In the 1960s, Sir John Charnley, CBE, FRS, posited that periprosthetic joint infection was one of the most difficult complications associated with total joint replacement.
While Charnley spent his career in orthopedics whittling down the infection rate from 10% to 1.5%, infection still remains one of the major complications for TJR today.
Image: Anoop K. Prasad, MD, PhD
“Whilst [PJI] may have a low incidence rate, 1% to 2%, [joint replacements are] done at such a high volume. You are talking about more than one million joint replacements,” Anoop K. Prasad, MD, PhD, a hip and knee arthroplasty attending at Harvard Medical School and Massachusetts General Hospital, told Healio. “The data on the survival rate of prosthetic joint infection is close to cancer — or worse than a lot of cancers — which nobody understood or knew. That is something that we are all learning now.”
In a 2025 meta-analysis, Michael S. Ramos, MS, and colleagues reported PJI after total hip arthroplasty yielded an overall mortality rate of 11% at 40.3 months. This is in comparison to a 5-year mortality rate of 11% and 1% for breast and prostate cancer, respectively. A systematic review in The Journal of Arthroplasty also showed a 5-year mortality rate of 21.64% after two-stage exchange for PJI after total knee arthroplasty.
The statistic that “up to one in five people may die in 5 years of a prosthetic joint infection” is an underfunded, underdiscussed problem, according to Prasad.
“We need to look at this like a cancer,” he said. “That would be a good way to frame the argument, because it is an extremely important problem that is underresourced.”
Multidisciplinary approach
One of the most important nonsurgical factors in PJI outcomes is collaboration between clinical departments, according to Jessica Seidelman, MD, MPH, medical director of infection prevention at Duke Health Integrated Practice and hospital epidemiologist.
A retrospective analysis showed multidisciplinary involvement in the treatment of PJI to be the highest predictor for success. Researchers also found a 100% cure rate when a dedicated multidisciplinary team performed a debridement, antibiotics and implant retention (DAIR) procedure vs. a 48% cure rate when the procedure was performed by a team of only orthopedic surgeons.
Jessica Seidelman
“The best outcomes happen when [orthopedic surgeons and infectious disease physicians are] in the same room, looking at the same patient, making the decisions together,” Seidelman told Healio. “A coordinated clinic model, where the patient sees both of us at the same time, is the ideal situation.”
In addition to multidisciplinary treatment, Prasad said more collaboration is needed between centers themselves, particularly in the area of research.
“What is needed now is much more collaboration,” he said. “The numbers needed [for trials] are so much higher to demonstrate an effect that you cannot do it in one institution. If you look at things that we use all the time — like cholesterol drugs and [blood pressure] medication — that stuff never came out of one unit. That was thousands of patients across multiple centers.”
Postcode lottery
But the challenge becomes how to make these specialized, multidisciplinary institutions accessible for every patient diagnosed with a PJI, according to Laura K. Certain, MD, PhD.
Laura K. Certain
“This is a big country, and a lot of people with prosthetic joints live in places where they might not be able to access those larger academic medical centers,” Certain, a clinical associate professor in the department of medicine division of infectious diseases and adjunct associate professor in the department of orthopedics at the University of Utah School of Medicine, told Healio. “I live in Utah, and many of my patients already are traveling 8 hours from Montana to get their care. It is not clear to me how a center for excellence works for the more rural population.”
Certain said most patients who travel long distances for care do not follow up with the infectious disease specialist if appointments with their surgeon are scheduled on separate days. Although her institution has embedded infectious disease doctors interested in orthopedic infections into the university’s orthopedic surgery clinic, Certain said not every practice has the resources to do this.
“Not all orthopedic surgeons practicing in the U.S. have an infectious disease doctor in their county,” Certain said. “For those who are fortunate enough to have an infectious disease doctor, and even more fortunate to have one who is interested in orthopedic infections, I would ask the surgeons to recognize that our infectious disease doctors are here to help.”
In addition, Prasad said replicating good results for PJI treatment outside of centers of excellence is “like a postcode lottery,” where not all physicians are created equal.
“There are multiple centers [of excellence], but most of them are from a few high-volume, well-respected surgeons,” Prasad said. “That becomes difficult when you are recommending something as a guideline. Studies done in the past show that what has been done and achieved in centers of excellence are not replicable throughout.”
PJI defined
Another area of concern in PJI treatment is the lack of current, up-to-date guidelines and definitions, with the most recent PJI criteria published in 2021.
“In my view, there are no current universally accepted guidelines on the management of prosthetic joint infection,” Certain said. “That said, there are general accepted practices and standards of care based on guidelines from the Infectious Diseases Society of America in 2012 and research that has come out since those guidelines and general expert consensus.”
As far as definitions go, Ken Urish, MD, PhD, associate medical director at the University of Pittsburgh Medical Center’s Magee Bone and Joint Center and the director of the Arthritis and Arthroplasty Design Laboratory, said a new unified definition for PJI is expected to be released in the latter half of 2026. This definition was established at the Unified PJI Definition Task Force’s 2025 International Consensus in Istanbul, Turkey.
Ken Urish
“It is a new unified definition for PJI because there have always been some subtle differences in diagnostics criteria for when an implant is infected or not,” Urish told Healio.
Despite PJI not previously having universal guidelines, Seidelman said guidelines from different orthopedic and infectious disease societies have “improved standardization.”
“Shared definitions and algorithms have been transformative for research quality improvement and our day-to-day communication,” Seidelman said.
However, if patient care is fragmented, the guidelines can only help so much, according to Seidelman.
“When you have a committed multidisciplinary team managing a high volume of these infections, adherence to these evidence-based guidelines improves, decision making is sharper and those outcomes follow,” Seidelman said. “My honest view is that guidelines are necessary, but they are not going to solve the problem. We need to build these specialized team-based infrastructures to deliver on them consistently.”
In addition to better protocols and definitions, Urish said more prospective studies on PJI treatment are needed to provide better avenues of treatment and reduce the risk for chronic infection.
“Our outcomes are bad, and a big portion of that is because once [a joint is] infected, it is difficult to get rid of the biofilm, which has a high tolerance to antibiotics,” Urish said. “The pathologic state of bacteria when it is in the body sets up a biofilm right away. You can have an atomic dose of antibiotics around it, and it is still going to take 5 days to get rid of it.”
Research concerns
As care teams look for better ways to disrupt biofilm, deliver antibiotics and monitor patients, Urish said the diagnosis and treatment of PJI is a multifaceted challenge requiring a “tool belt” of solutions only future research can provide.
On the side of infectious disease, diagnosis remains a primary research concern, especially in cases where a patient is symptomatic, but advanced culture techniques and sequence-based diagnostics fail to pinpoint the bacteria or fungi causing it. Another question unanswered by current research is which patients benefit from longer courses of antibiotics, according to Certain.
“Often, [patients who undergo a DAIR procedure] are put on prolonged, sometimes indefinite, courses of antibiotics,” she said. “The DATIPO trial showed us that for those patients, 12 weeks is better than 6 weeks. But we do not know if 6 months is better than 3 months or 12 months is better than 6 months. Do some people need it for 5 years or forever? That is an unanswered question, and a hard one to answer.”
One factor that makes studying PJI difficult is its low incidence rate and the high number of replacements a researcher must observe to build a credible trial, according to Prasad.
“If there is a 10% chance of something making a difference, it is easy to construct a study. When you say there is 1% or less, it is difficult,” he said. “The studies have been very difficult to organize, because the numbers required are massive. When you have massive numbers, the number of variables changes massively, and then it gets lost in the noise. These small sizes of infection cannot be accounted for.”
‘You can never eliminate risk’
In the future, Prasad said he hopes “that we can try and predict who is going to have a problem more accurately and pick it up sooner.”
According to Prasad, the reason for this race against the clock lies with treatment prognosis, where early interventions can help a patient avoid larger procedures, like revisions. Each revision procedure also leads to a higher risk for PJI, Seidelman said.
“The risk is lifelong and not confined to just the perioperative window,” Seidelman said. “The number of PJIs we are going to be taking care of is climbing. Any one patient’s risk has not changed all that much. It is the sheer number of people affected that is growing, because we are operating on so many more patients, and they are living longer, requiring more revisions.”
Despite obstacles, Prasad is eager for what is to come — if researchers can work together and look at PJI “holistically.”
“It is an exciting time in terms of new ways of delivering antibiotics. There is exciting work in China, where they are doing rapid two stages,” Prasad said. “There are many — from a diagnosis perspective — things being looked at. From a treatment perspective, different materials. … But collaboration is key in terms of the final outcome.”
While research has helped establish preoperative, perioperative and postoperative optimization strategies for patients undergoing joint replacement to mitigate PJI risk, including the importance of smoking cessation, IV antibiotics during the procedure and antibiotics after, Prasad said the chances of developing an infection is never zero and all care teams can do is “control the factors that can be controlled.”
“You can never eliminate risk. That just has to be accepted,” he said. “Infection is one of those things where it is so multifactorial that there will always be a risk of it occurring. We are just trying to reduce that.”
For more information:
Laura K. Certain, MD, PhD, can be contacted at laura.certain@hsc.utah.edu.
Anoop K. Prasad, MD, PhD, wishes to be contacted through Timothy F. Sullivan at tsullivan11@mgb.org.
Jessica Seidelman, MD, MPH, can be contacted at jessica.seidelman@duke.edu.
Ken Urish, MD, PhD, can be contacted at ken.urish@gmail.com.
Sources/Disclosures
References:
Disclosures:
Certain reports being a paid consultant for Zimmer Biomet and medicolegal consultant for 3M. Prasad reports no relevant financial disclosures. Seidelman reports being a paid consultant for Osteal Therapeutics; a legal expert for DLA Piper, Faegre & Drinker and Nichol & Associates; and receives royalties from UpToDate as the author for pelvic osteomyelitis. Urish reports being an equity holder, consultant and member of the scientific advisory board for Osteal Therapeutics and Peptilogics; being the president of the Musculoskeletal Infection Society; and being a consultant for Onkos Surgical and Smith & Nephew.
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