Periprosthetic joint infection is one of the most challenging complications in hip and knee replacement. It can transform an operation intended to restore mobility into a prolonged course of additional surgery, antibiotics, rehabilitation, and uncertainty.
In Episode 45 of The Joint Replacement Podcast, I sat down with Jesse Otero, MD, PhD, an adult reconstruction surgeon at OrthoCarolina and professor of orthopedic surgery at Wake Forest, whose career has centered on some of the most difficult problems in joint replacement. We discussed how he built a busy practice by embracing complex cases, the personal experience that led him toward the study of joint replacement infection, how his team built a large PJI research registry, and important new evidence challenging the traditional approach to treating chronic infection.
Building a Practice by Taking the Cases Others Avoid
One of the most interesting parts of Dr. Otero’s career is how his practice began.
As a young surgeon returning to Iowa after fellowship, he spent a roughly 15-hour drive calling surgeons he knew in the area. His message was simple: if they had an infection, revision, or difficult joint replacement case they did not want to manage, he was willing to take it.
By the time he arrived, his clinic was filling up. His first 17 operative cases were infected revisions. Rather than competing with established surgeons for routine primary hip and knee replacements, he created a referral niche by becoming someone other surgeons could call when a case became complicated.
That experience contains an important lesson for young surgeons. Building a practice does not necessarily mean trying to duplicate what everyone else is doing. Developing expertise in an area where patients and referring physicians have an unmet need can be an entirely different path.
Why Periprosthetic Joint Infection Became Personal
Dr. Otero’s interest in PJI was not simply academic.
While he was a resident, his grandfather underwent knee replacement. After surgery, he sustained a fall while recovering in a nursing facility and ultimately was found to have a patellar tendon rupture. His subsequent course became increasingly complicated, including wound drainage, infection, antibiotic treatment, renal failure, and ultimately his death.
For a trainee who was simultaneously discovering how powerful joint replacement could be, the experience exposed the other side of arthroplasty.
Most hip and knee replacements do extremely well. But when major complications occur, the consequences can be profound.
Patients dealing with PJI may face repeated operations, long courses of antibiotics, loss of mobility, time away from work, financial pressure, and dependency on family members. There is also an enormous psychological burden. A patient who elected surgery hoping to regain his or her life may suddenly wonder whether life was actually better before the original joint replacement.
That experience helped shape Dr. Otero’s decision to devote much of his career to the patients experiencing the most difficult complications.
The Patients Who Have Been Told There Are No Options Left
There is a recurring theme throughout our conversation: hope.
Dr. Otero is drawn to patients with recurrent infection, massive bone loss, failed prior operations, and other complications who may have already been told that there is little more that can be done.
Sometimes the most meaningful moment occurs before an operation even begins.
It is simply being able to tell a patient: we may not know exactly where this ends, but there is still something we can try.
That does not mean promising an outcome. Complex revision surgery is unpredictable, and complications can occur. Instead, it means being willing to take on a difficult problem while giving patients realistic expectations about what surgery may and may not accomplish.
How Do Surgeons Prepare for Extremely Complex Surgery?
Dr. Otero described an approach that will resonate with surgeons who routinely perform complex revision operations: mentally performing the case before entering the operating room.
He visualizes each step and repeatedly considers Plan A, Plan B, and Plan C. What happens if the implant will not come out? What if the remaining bone fractures? What reconstruction options need to be available?
He also shared advice from one of his mentors, Thomas Fehring, MD: when an unexpected complication occurs, sometimes the best first move is not immediately acting.
Instead, cover the wound, organize the problem, think through the options, call a colleague if necessary, and return with a deliberate plan rather than allowing the adrenaline of the complication to dictate the next step.
That mindset is particularly important in revision arthroplasty, where seemingly small decisions can dramatically change the remainder of an operation.
Turning a PJI Referral Center Into a Research Laboratory
One of the most impressive aspects of the OrthoCarolina program is how clinical volume has been transformed into research infrastructure.
Dr. Otero described a PJI registry containing approximately 5,500 patients with extensive clinical data. Historical cases were initially assembled retrospectively, followed by prospective collection as new patients entered the program. The database includes patient characteristics, laboratory results, infection criteria, organisms, antibiotics, treatments, and outcomes.
The advantage is powerful.
Instead of beginning every new research question by attempting to reconstruct years of medical records, investigators can start with a carefully maintained clinical registry.
It has also pushed the clinical program toward greater standardization. When multiple surgeons are studying the same condition, differences in antibiotic cement, debridement, irrigation, or postoperative treatment make outcomes more difficult to interpret.
Standardization creates an opportunity to identify what works, incorporate it into the protocol, and continue studying the results.
This is a model that extends well beyond infection. High-volume clinical practices may contain an extraordinary amount of information. The challenge is developing the infrastructure to collect it systematically.
One Stage or Two Stages for Chronic Joint Replacement Infection?
Perhaps the most important scientific discussion in this episode involves a major recent randomized trial.
For decades, the traditional U.S. treatment for many chronic periprosthetic joint infections has been a two-stage exchange.
During the first operation, the infected components are removed, the joint is extensively debrided, and an antibiotic-containing spacer is typically implanted. After a period of treatment, the patient returns for a second operation in which the spacer is removed and definitive hip or knee components are implanted.
A one-stage exchange attempts to accomplish both goals during a single operation: removal of the infected implants, aggressive debridement, and implantation of the definitive reconstruction during the same surgical episode.
The obvious question is whether eliminating the second operation comes at the cost of a higher risk of persistent or recurrent infection.
A 2026 prospective multicenter randomized trial led by Thomas K. Fehring, MD, with Jesse E. Otero, MD, PhD and colleagues, directly compared these strategies. A total of 323 patients were randomized to one-stage or two-stage treatment, with 258 patients available for two-year follow-up. The trial deliberately included clinically important groups such as patients with draining sinuses, resistant organisms, and significant comorbidities.
At two years, clinical success was:
97% with one-stage exchange
91% with two-stage exchange
The study demonstrated that one-stage treatment was statistically noninferior to two-stage treatment under the protocol studied. Fehring et al. also reported approximately threefold higher odds of overall success with one-stage treatment in regression analysis, although the study was designed around the noninferiority question rather than proving superiority.
Those are potentially practice-changing findings.
But the Protocol Matters
The conclusion should not be that every infected joint replacement should now undergo a one-stage revision.
The protocol used by Fehring et al. was extremely structured.
The operations involved radical debridement, a defined irrigation protocol, complete separation between the contaminated portion of the procedure and reconstruction, new sterile instruments, re-prepping and draping, and standardized antimicrobial treatment. Dr. Otero emphasized during our discussion that reproducing the result means reproducing the discipline of the protocol.
The published study also specifically cautions against extrapolating the findings beyond the population studied. Patients with prior revision implants, culture-negative infections, fungal infections, immunosuppression, or wounds that could not be closed primarily were among the groups for whom these results should not automatically be generalized.
So the takeaway is more nuanced than “one stage is better.”
It is that for appropriately selected patients with chronic infection following primary total hip or knee arthroplasty, a rigorously performed one-stage exchange can achieve infection-control outcomes at least comparable to the traditional two-stage strategy.
Why One Stage Could Matter So Much to Patients
The importance of the study extends beyond percentages.
A two-stage exchange asks a patient to recover from a major revision operation while knowing another major operation remains ahead. Depending on the spacer and reconstruction, patients may spend months with reduced function before beginning the recovery process again after reimplantation.
A successful one-stage exchange potentially eliminates that second major surgery.
Dr. Otero noted that patients who receive their definitive implants during the initial operation can begin recovering around a stable final reconstruction rather than waiting for another procedure. In his experience, when appropriately selected patients are offered both strategies and understand the emerging evidence, the appeal of avoiding a second operation is substantial.
What Comes Next in PJI?
Despite progress, periprosthetic joint infection remains one of the major unsolved problems in joint replacement.
Dr. Otero and his collaborators continue to investigate new approaches, including laboratory work, new models of infection, devices, treatment strategies, and continued analysis of their growing clinical registry.
The broader lesson from this conversation may be just as important as any individual technique.
Complex patients create difficult clinical problems. But when high-volume care is paired with standardized protocols, prospective data collection, multidisciplinary collaboration, and a willingness to challenge established dogma, those same patients can help us learn how to provide better care to the next person who develops the same complication.
And that is ultimately the goal.
Reference
Fehring TK, Otero JE, Fehring KA, Curtin BM, Springer BD, Della Valle CJ, Parvizi J, Hietpas K, Ready A, Odum SM; PJI Study Group. One-Stage Versus Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection: A Prospective Randomized Trial. J Bone Joint Surg Am. 2026;108(14):1070-1082. doi:10.2106/JBJS.25.00713.
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One-Stage vs Two-Stage Revision for Joint Replacement Infection | Jesse Otero, MD, PhD
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Dr. Jesse Otero discusses complex revision surgery, periprosthetic joint infection, PJI research, and the Fehring et al. randomized trial comparing one-stage versus two-stage exchange.