Decision-making process in periprosthetic infection treatment management: a multimodal approach

Introduction

Musculoskeletal infection remains a challenging post-operative complication amongst orthopaedic surgeons, requiring multi-specialty coordination given its potential for irreparable damage. Periprosthetic infection outcomes are driven by a multitude of factors including the causative pathogen’s virulence, immunocompetency and associated comorbidities of the patient, anatomic location of the prosthesis, age of the patient, and the extent of the bone and soft tissue loss. The goal remains to eradicate the infection while salvaging the limb as much as possible without compromising the patient’s functional status. Understanding the specific indications, patient characteristics, and infection parameters is crucial for selecting the most appropriate approach and optimizing outcomes. However, the most well-prepared orthopaedic surgeon has also already considered the next options in the unfortunate event if the infection persists. There is continuous debate on indications for the best methodology of treating periprosthetic infection. We provide an overview on the different options available with suggestions on when their use would be most appropriate.

Three main surgical options

Understanding the nuances and evidence supporting DAIR and staged debridement approaches is crucial in guiding clinical decision-making and optimizing the management of musculoskeletal infections. Individual patient characteristics such as infection severity, implant stability, and soft tissue condition determine whether DAIR, one-stage, or two-stage revision will be selected for initial treatment. DAIR consists of aggressive debridement of infected tissues, intravenous antibiotics, and retention of the original implant with PE insert exchange, while staged debridement involves a multistep approach with implant removal, thorough debridement, and immediate versus delayed reimplantation. There is significant variability in treatment success of preliminary management of periprosthetic infections with DAIR, one-stage, or two-stage revisions as demonstrated in Table 1.

DAIR

DAIR aims at retaining the implant with thorough debridement and irrigation with PE insert exchange. It has shown favorable results in cases of early infections, well-fixed implants, and infections caused by low-virulence organisms [1] Kunutsor SK, Beswick AD, Whitehouse MR, Wylde V, Blom AW. Debridement, antibiotics and implant retention for periprosthetic joint infections: A systematic review and meta-analysis of treatment outcomes. J Infect. 2018;77(6):479-88.. It is commonly indicated in situations where the infection is identified acutely (usually less than 3 weeks after symptom development), the causative pathogen has low virulence, or the patients cannot tolerate an explant either due to medical conditions or limited life expectancy. Success rates of eradicating the infection via DAIR also vary depending on the infection location with a higher success rate in a total hip replacement (60-83%) as opposed to a total knee replacement (55-70%) [1], Kunutsor SK, Beswick AD, Whitehouse MR, Wylde V, Blom AW. Debridement, antibiotics and implant retention for periprosthetic joint infections: A systematic review and meta-analysis of treatment outcomes. J Infect. 2018;77(6):479-88.[2] Scheper H, Gerritsen LM, Pijls BG, Van Asten SA, Visser LG, De Boer MGJ. Outcome of Debridement, Antibiotics, and Implant Retention for Staphylococcal Hip and Knee Prosthetic Joint Infections, Focused on Rifampicin Use: A Systematic Review and Meta-Analysis. Open Forum Infect Dis. 2021;8(7):ofab298.. Radical debridement is one of the keys for success but has technical limitations with implants in place especially for TKA. Further risk factors that have been shown to significantly increase risk of failure after DAIR include insufficient soft tissue coverage, patients in the McPherson systemic host C group, and signs of chronic infection such as a sinus tract [3] Zaruta DA, Qiu B, Liu AY, Ricciardi BF. Indications and Guidelines for Debridement and Implant Retention for Periprosthetic Hip and Knee Infection. Curr Rev Musculoskelet Med. 2018;11(3):347-56.. Additionally, DAIR has low success in immunocompromised patients with findings that risk of amputation for failed limb salvage increases by more than 6 times in such patients [4], Jeys LM, Grimer RJ, Carter SR, Tillman RM. Periprosthetic infection in patients treated for an orthopaedic oncological condition. J Bone Joint Surg Am. 2005;87(4):842-9.[5] Haijie L, Dasen L, Tao J, Yi Y, Xiaodong T, Wei G. Implant Survival and Complication Profiles of Endoprostheses for Treating Tumor Around the Knee in Adults: A Systematic Review of the Literature Over the Past 30 Years. J Arthroplasty. 2018;33(4):1275-87 e3.. DAIR offers the potential for implant salvage, minimizing the need for additional surgeries and preserving limb function, and is associated with shorter hospital stays, reduced costs, and decreased morbidity. However, DAIR may be less effective in cases of chronic or deep-seated infections, implant loosening, or compromised soft tissues.

One-Stage Revision

One-stage revision removes infected components with implantation of new prosthetic components during a single operation [6] Kildow BJ, Springer BD, Brown TS, Lyden E, Fehring TK, Garvin KL. Long Term Results of Two-Stage Revision for Chronic Periprosthetic Hip Infection: A Multicenter Study. J Clin Med. 2022;11(6).. This method is beneficial due to the fewer number of procedures required and some studies have demonstrated equal or better functional outcomes relative to those after two-stage revisions [7] Klemt C, Tirumala V, Oganesyan R, Xiong L, van den Kieboom J, Kwon YM. Single-Stage Revision of the Infected Total Knee Arthroplasty Is Associated With Improved Functional Outcomes: A Propensity Score-Matched Cohort Study. J Arthroplasty. 2021;36(1):298-304.. However, it is only suitable for patients that meet certain criteria including sufficient and stable soft tissue, a well-identified causative organism, and absence of sinus tracts, which may also bias functional outcome results [8], Negus JJ, Gifford PB, Haddad FS. Single-Stage Revision Arthroplasty for Infection-An Underutilized Treatment Strategy. J Arthroplasty. 2017;32(7):2051-5.[9] Castellani L, Daneman N, Mubareka S, Jenkinson R. Factors Associated with Choice and Success of One- Versus Two-Stage Revision Arthroplasty for Infected Hip and Knee Prostheses. HSS J. 2017;13(3):224-31.. Furthermore, patients with megaprostheses such as a total femur a one-stage revision might be preferred since an adequate mega spacer will immobilize the patient [10] Holzer G, Windhager R, Kotz R. One-stage revision surgery for infected megaprostheses. J Bone Joint Surg Br. 1997;79(1):31-5..

Two-Stage Revision

Staged revision surgery is often preferred for chronic or recurrent infections, implant loosening, and infections caused by highly virulent organisms. Although involving additional surgeries and longer treatment duration, it provides an opportunity for thorough debridement, resolution of infections, and implant exchange with improved stability. The staged approach allows for the assessment of infection control and optimization of local tissue conditions before reimplantation. Compared to single stage, two-stage revision requires prolonged hospitalization and is associated with higher rates of functional impairment and morbidity. Patients with chronic infections are at increased risk for more virulent pathogens or polymicrobial infections and usually present with not only poor-quality soft tissues, but also greater bone loss. As such, these patients are initially managed with a two-stage revision due to its greater potential for preserving bone stock than a one-stage revision [11] Wichern EM, Zielinski MR, Ziemba-Davis M, Meneghini RM. Contemporary 2-Stage Treatment of Periprosthetic Hip Infection with Evidence-Based Standardized Protocols Yields Excellent Results: Caveats and Recommendations. J Arthroplasty. 2020;35(10):2983-95.. Use of a mobile articulating spacer during the interim period permits early functional mobilization while maintaining joint stability and delivering local antibiotic therapy. This method has even shown to be effective utilizing large intramedullary spacers for large segmental bone defects at the knee [12] Ippolito JA, Thomson JE, Rivero SM, Beebe KS, Patterson FR, Benevenia J. Management of Large Segmental Bone Defects at the Knee With Intramedullary Stabilized Antibiotic Spacers During Two-Stage Treatment of Endoprosthetic Joint Infection. J Arthroplasty. 2021;36(6):2165-70..

Bone defect management

Extensive bone defects resulting from chronic infections are common and durable fixation remains a challenge. The introduction of porous metal wedges, cones and sleeves have significantly improved the fixation options for hips and knees. Bone transport, a technique based on the principles of distraction osteogenesis, has gained increasing attention for diaphyseal bony defects as a promising solution for managing such cases. Bone transport has demonstrated favorable outcomes however, for PJI it plays no role and will not be discussed here.

Overview of periprosthetic infection management

Patient care and counseling requires consideration of possible future reoperations and whether patients would be able to tolerate future procedures, as outlined in Figure 1. Patients who are indicated for further surgical management, regardless of the first procedure performed, the next step after failed infection control consists of a two-stage revision. If the infection continues to persist, more extensive surgical interventions are required [13] Fagotti L, Tatka J, Salles MJC, Queiroz MC. Risk Factors and Treatment Options for Failure of a Two-Stage Exchange. Curr Rev Musculoskelet Med. 2018;11(3):420-7.. Hip infections would require Girdlestone resection arthroplasty and very rare hip disarticulation. Unrelenting knee infection would be managed with arthrodesis, and if the infection continued to be poorly controlled, an above knee amputation (AKA). Given the high rates of morbidity and minimal improvement in functional and health status outcomes with additional limb-salvaging procedures, surgical attempts to limb-salvage should not exceed 4-6 procedures. After this many surgeries, the likely return on improvement in health outcome is diminished making amputation the best next step.

Resection Arthroplasty

Resection arthroplasty procedures follow failed attempts at DAIR and staged revisions. For complicated hip infections, the Girdlestone procedure, while not frequently utilized, has shown to be effective in controlling infection rates [14], Vincenten CM, Den Oudsten BL, Bos PK, Bolder SBT, Gosens T. Quality of life and health status after Girdlestone resection arthroplasty in patients with an infected total hip prosthesis. J Bone Jt Infect. 2019;4(1):10-5.[15] Kantor GS, Osterkamp JA, Dorr LD, Fischer D, Perry J, Conaty JP. Resection arthroplasty following infected total hip replacement arthroplasty. J Arthroplasty. 1986;1(2):83-9.. However, functional results have not been very favorable with more than 90% of patients experiencing persistent pain and 83% are minimal community ambulators [14] Vincenten CM, Den Oudsten BL, Bos PK, Bolder SBT, Gosens T. Quality of life and health status after Girdlestone resection arthroplasty in patients with an infected total hip prosthesis. J Bone Jt Infect. 2019;4(1):10-5.. Resection arthroplasty for infected knees should be performed for wheelchair bound patients only.

Arthrodesis

Arthrodesis has a limited role in infected THA since resection arthroplasty represents the better alternative. When attempting to control TKA infections, arthrodesis can be a part of the staged revision procedures either by using this as a definitive primary procedure or after failed revision surgeries. It is usually indicated in circumstances involving an inadequate extensor mechanism, highly virulent organisms, or multiple failed attempts at limb salvaging [16] Mabry TM, Jacofsky DJ, Haidukewych GJ, Hanssen AD. Comparison of intramedullary nailing and external fixation knee arthrodesis for the infected knee replacement. Clin Orthop Relat Res. 2007;464:11-5.. Arthrodesis has a high success at eradicating infection with success rates over 90%, although complication rates are relatively high at 40%. It has been shown to have better functional outcomes than above-the-knee amputations [17] Wang M, Liu T, Xu C, Liu C, Li B, Lian Q, et al. 3D-printed hemipelvic prosthesis combined with a dual mobility bearing in patients with primary malignant neoplasm involving the acetabulum: clinical outcomes and finite element analysis. BMC Surg. 2022;22(1):357.. However, Carr et. al determined significantly higher post-operative complication rates found in knee arthrodeses relative to above knee amputations, as summarized in Table 2 [18] Carr JB, 2nd, Werner BC, Browne JA. Trends and Outcomes in the Treatment of Failed Septic Total Knee Arthroplasty: Comparing Arthrodesis and Above-Knee Amputation. J Arthroplasty. 2016;31(7):1574-7..

Knee arthrodesis, common in the early 1900s, is an uncommon outcome of failed TKA. The most common reason for knee arthrodesis in modern times is failed treatment of PJI with TKA [19] Conway JD, Mont MA, Bezwada HP. Arthrodesis of the knee. J Bone Joint Surg Am. 2004;86(4):835-48.. Patients with substantial metaphyseal bone loss, inadequate ligamentous restraints, multiple failed revisions, inadequate soft tissue coverage with loss of extensor mechanism and infection with virulent organisms should be considered for knee arthrodesis. Patients with failed two stage reimplantation may be candidates for arthrodesis. There are newer implants available that are considered arthrodesis endoprostheses that can bridge limited bone defects and allow for weight bearing [20] Luyet A, Steinmetz S, Gallusser N, Roche D, Fischbacher A, Tissot C, et al. Fusion rate of 89% after knee arthrodesis using an intramedullary nail: a mono-centric retrospective review of 48 cases. Knee Surg Sports Traumatol Arthrosc. 2023;31(4):1299-306.. Given the low functional outcomes of AKA versus arthrodesis, when treating a patient who requires multiple revision surgeries, earlier intervention with an arthrodesis is considered before amputation is the only viable option remaining.

Amputation

Amputations are an absolute last resort when considering treatment options for infected TKA. They are usually considered in cases of severe sepsis, unrelenting local infection with concomitant massive bone loss and uncontrollable pain [21] Mousavian A, Sabzevari S, Ghiasi S, Shahpari O, Razi A, Ebrahimpour A, et al. Amputation as a Complication after Total Knee Replacement, is it a Real Concern to be Discussed?: A Systematic Review. Arch Bone Jt Surg. 2021;9(1):9-21.. Amputations are rarely considered due to the high percentage of low functional outcomes given the high energy expenditure required with at least half of patients ultimately requiring a wheelchair (22). This is why when treating a patient who requires multiple revision surgeries, earlier intervention with an arthrodesis is considered before amputation is the only viable option remaining.

In some cases, above knee amputation (AKA) for a chronically infected total knee arthroplasty is the only option. There have been several reports on the subject and various contributing factors can be identified. Severe soft-tissue loss, more than 6 reoperations, and prior flap reconstruction, correlate with the need for AKA [23] Khanna V, Tushinski DM, Soever LJ, Vincent AD, Backstein DJ. Above knee amputation following total knee arthroplasty: when enough is enough. J Arthroplasty. 2015;30(4):658-62.. Due to poor functional outcomes, amputations are considered an absolute last resort when considering treatment options for infected TKA [24] Sierra RJ, Trousdale RT, Pagnano MW. Above-the-knee amputation after a total knee replacement: prevalence, etiology, and functional outcome. J Bone Joint Surg Am. 2003;85(6):1000-4.. Infection is the most common complication that results in the rare indication for an amputation after a TKA (0.025%) due to the higher prevalence of infection than other complications such as vascular injury and compartment syndrome (21). Similarly, hip disarticulation is a rare outcome of a chronically infected total hip arthroplasty, occurring about 0.3% of hip PJIs. Options such as Girdlestone can be chosen earlier and may eliminate the need for hip amputation (25). Patients with PJI after tumor megaprostheses are at higher risk of amputation at all levels. Jeys and Grimer found that amputation rates due to infection vary according to anatomic location of the prosthesis with the highest rates occurring at the tibia (7.8%), distal femur (2.4%), and pelvis (2.0%) [26] Jeys LM, Grimer RJ, Carter SR, Tillman RM. Risk of amputation following limb salvage surgery with endoprosthetic replacement, in a consecutive series of 1261 patients. Int Orthop. 2003;27(3):160-3..

Mozella found that the incidence of amputation as a result of complications from TKA was 0.41% incidence with recurrent infection responsible for 81% of cases [28] Mozella AP, da Palma IM, de Souza AF, Gouget GO, de Araujo Barros Cobra HA. Amputation after failure or complication of total knee arthroplasty: prevalence, etiology and functional outcomes. Rev Bras Ortop. 2013;48(5):406-11.. Failure after DAIR for PJI of TKA was significantly associated by a number of factors including the presence of a sinus tract, infection due to methycillin-resistant Staph. Aureus, the immunocompromised status of the patient, treatment delays, relatively short antibiotic duration, and retention of exchangeable prosthetic components [27] Qasim SN, Swann A, Ashford R. The DAIR (debridement, antibiotics and implant retention) procedure for infected total knee replacement - a literature review. SICOT J. 2017;3:2..

With significant surgeries such as an AKA, it is relevant to evaluate the functional and psychosocial impact on patients. Of the patients that were amputated, 44% were utilizing prostheses while 62.5% were functionally walking [28] Mozella AP, da Palma IM, de Souza AF, Gouget GO, de Araujo Barros Cobra HA. Amputation after failure or complication of total knee arthroplasty: prevalence, etiology and functional outcomes. Rev Bras Ortop. 2013;48(5):406-11.. Ambulatory status after AKA has not shown to significantly worsen- about half of patients continuing to be nonambulatory while about a quarter remain home ambulators or community ambulators, respectively [29] George J, Newman JM, Caravella JW, Klika AK, Barsoum WK, Higuera CA. Predicting Functional Outcomes After Above Knee Amputation for Infected Total Knee Arthroplasty. J Arthroplasty. 2017;32(2):532-6.. In Orfanos’ retrospective analysis identified a 50% mortality rate at 5 years after AKA for PJI [30] Orfanos AV, Michael RJ, Keeney BJ, Moschetti WE. Patient-reported outcomes after above-knee amputation for prosthetic joint infection. Knee. 2020;27(3):1101-5.. The majority of patients in their study (86%) were satisfied with their AKA and 42% reported that in hindisight, they would have done it sooner [30] Orfanos AV, Michael RJ, Keeney BJ, Moschetti WE. Patient-reported outcomes after above-knee amputation for prosthetic joint infection. Knee. 2020;27(3):1101-5..

Currently, surgical treatment decision-making for periprosthetic infection requires careful balancing between preparing for feared and unknown outcomes while prioritizing patient safety and preservation of function. Given its ubiquity within orthopaedic surgery, we must continue to develop and improve treatment strategies and protocols to minimize infection risk.