CORR Insights®: What are the Factors Associated With Re-revision After One-stage Revision for Periprosthetic Joint Infection of the Hip? A Case-control Study

Where Are We Now?

Perhaps the most vexing problem in all of arthroplasty is managing periprosthetic joint infection (PJI). Although we have made strides in identifying those patients who may be at highest risk for this potentially devastating complication, the overall incidence of approximately 1% has not changed substantially since Sir John Charnley adopted the use of body exhaust suits and preoperative antibiotics nearly 50 years ago [4]. One may take this to mean that PJI is not entirely avoidable, and that management and treatment of this complication may require as much attention, or more so, than its prevention.

The mainstays of PJI treatment have included débridement and implant retention (DAIR), single-stage exchange, and two-stage exchange; two-stage exchange is the most-commonly used approach for the treatment of chronic PJI in North America, but this is not the case in all parts of the world. In addition to the morbidity associated with the two-stage exchange, its protracted convalescent period, and the possibility that this approach may not reliably eradicate infection, arthroplasty surgeons and hospital systems now recognize that there is a real risk of death as well as substantial costs associated with this approach. Because of that, dogmatic adherence to this treatment as a one-size-fits-all approach may fail our most vulnerable patients. Evidence supports single-stage exchange as a technique that may deliver nearly comparable results to the two-stage approach in terms of infection control in well-selected patients, leading to increased enthusiasm for this technique and a growing number of publications on this issue in the last several years [8, 10-12]. Select centers in Europe, notably the institution from which Abdelaziz and colleagues [1] hail, have decades’ worth of experience with single-stage exchange, and their findings should serve to frame future approaches to refining this technique.

While not all patients with chronic PJI are candidates for single-stage exchange, criteria exist that help identify those who are not, such as patients with highly resistant infecting organisms with no appropriate antimicrobials, systemic sepsis, poor bone stock, persistent infection following a prior single-stage exchange, or culture-negative infections [9]. Most patients, however, do not meet these exclusion criteria and therefore may be suitable candidates for single-stage exchange. It should be recognized that results published from these specialized centers reflect the approach by a highly focused multidisciplinary group of clinicians who employ strict management protocols with respect to surgical and medical treatments. Most of the studies on the results of single-stage exchange have focused upon the ability of this technique to control infection, though a few have also taken a broader view of patient outcomes and analyzed all potential causes of subsequent surgery, similar to the current study [1].

In the current study [1], the authors found that the most-common reason for repeat surgery after a single-stage exchange is not recurrent infection, but rather hip instability/dislocation. These findings emphasize the need for meticulous surgical technique, not just for infection control, but also for implant positioning, maintenance of soft-tissue integrity, and consideration of advanced technologies, such as dual articulation bearing constructs. Of those patients undergoing a revision after the single-stage exchange for infection (40/121), 58% involved a new organism. Moreover, in those who had a rerevision, 44% (19/43) were again caused by infection [1]. In most of these, infection appears to be the unsolvable problem.

Where Do We Need To Go?

Much effort has been directed towards understanding specific patient factors for infection risk, the failure of current treatments to control infection, surgical technique, and antimicrobial therapies. However, the evolution of surgical technique may soon plateau, and antimicrobial options continue to be limited. Three areas of future interest to advance this field include research to develop a more-nuanced understanding of why certain patients develop PJI (and fail to respond to treatment), implant-related development, and the evolution of specialized teams and centers to manage this problem.

First, it was disheartening to learn that patients who undergo repeat revision for infection following a one-stage revision for PJI do so because of a new infecting organism, rather than because of persistence of the original pathogen [1]. Despite meticulous surgical technique and antimicrobial therapies afforded patients undergoing single-stage exchange, some patients will develop entirely new infections. This cannot be attributed to simple bad luck. Some degree of immune dysfunction is likely to be at the core of this problem, with a potential underlying cause being as straightforward as nutritional deficiencies or as complex as altered immune system interaction with the patient’s microbiome leading to impaired immune function. Additionally, a recent study [2] has demonstrated a genetic link between relatives who develop PJI, pointing to a yet-to-be-identified genetic basis for PJI. A deeper understanding of this will require future collaboration between not only surgeons and infectious diseases specialists, but also geneticists and immunologists assisted by the blossoming field combining biostatistics and machine learning.

Second, there is an understanding that prolonged antimicrobial therapy into the joint space, both at the index procedure and time of infection treatment, portends lower infection rates [2, 8]. Whether in the form of a detergent, iodinated solution, or antibiotics, local adjuvant treatment appears beneficial. While joint implant-related problems that plagued the previous generations of THAs (such as loss of fixation and wear) have been largely solved, the next wave of improvements will focus on implant-related solutions to PJI, such as antifouling surfaces or local drug elution [5].

Finally, the European model of specialized centers based on multidisciplinary care may be unfamiliar to some clinicians in the United States who treat PJI independently (and sometimes even without the assistance of an infectious disease specialist). But one does not have to look beyond the proliferation of cancer centers in most healthcare systems (including in the United States) for examples of integrated health-systems' approaches to managing complex diseases. In the United States now, there is a clear disincentive for caring for patients with PJI due to cost, time, and the perception of poor outcomes, but this does not have to be the case. Clinicians and centers with the skill and expertise to tackle this challenging problem of PJI should be organized, recognized, and rewarded accordingly.

How Do We Get There?

An improved understanding from collaborative studies may help to further refine the eligibility for less-morbid treatments, whether DAIR or single-stage exchange, for PJI. Multicenter studies are underway with support from specialty societies, such as the Knee Society and large academic centers (ClinicalTrials.gov; Identifier: NCT02734134). Moving forward, such collaborations can contribute towards centralized databases from which to assess potential associations between risk factors and outcomes.

To better understand the potential genetic influences of this disease, existing technologies and data repositories should be leveraged in the near future. Patients at risk for PJI, or those who have developed PJI, will soon have genetic analysis that will populate these repositories. Given the substantial decline in cost for this type of analysis, its use should proliferate as should a deeper understanding of this association. Commonly used implant materials, such as polyethylene, are currently being designed to be drug-eluting, and clinical studies to evaluate its effectiveness should not be difficult to perform, given that its use can be in line with current surgical techniques and implants [7].

Finally, a realistic understanding of the societal implications for PJI must be recognized by healthcare stakeholders [6]. Continued research into the economic and societal implications of this disease will help spur policy change by insurers and Centers for Medicare & Medicaid Services. An investment in the redesign of care of patients with PJI must be based upon properly funded regional specialty centers with a care team dedicated to infection treatment that mirrors the economic impact of this disease. Individual efforts, though important and the historical paradigm in this field, cannot compare to a multifaceted systems approach to this devastating problem. Periprosthetic joint infection should not be considered singularly as a complication, but rather a disease unto itself. Accordingly, and if appropriate standards of care are met, patients, clinicians, and medical centers should not be penalized for this ‘complication’ through the withholding of reimbursement, but rather should be transparent in its reporting so that professional societies, such as the American Academy of Orthopedic Surgeons, may be armed with accurate data when lobbying payors and policy makers.