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Periprosthetic joint infection (knee)

111 citationsUpdated Sep 2026

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Overview

Periprosthetic joint infection (PJI) is a severe complication of total knee arthroplasty that generates high costs for public health systems [23]. Patient factors remain the most important predictors of early prosthetic joint infection [3], with a history of treated septic arthritis conferring high risk, particularly in knee arthroplasty compared to hip arthroplasty [1]. Wound complications after total knee arthroplasty increase the risk of deep infection, as well as cost, length of hospitalization, and readmission rates [70]. Polymicrobial infections represent a substantial proportion of all PJI occurrences [27].

Diagnosis requires investigation for PJI in all patients undergoing revision arthroplasty [9]. Diagnostic criteria and treatment approaches vary globally due to logistical constraints and resource availability [11], and early-postoperative versus late-chronic infections may require different thresholds for serological markers [71]. In North America, two-stage revision arthroplasty is the treatment of choice for chronic periprosthetic infection of the hip and knee [6]. Operative débridement remains the single most important treatment for infection at the site of a knee prosthesis [8]. Debridement, antibiotics, and implant retention (DAIR) is a viable and safe option when performed early after primary surgery with a relevant postrevision antibiotic regime [66]. The success of prosthesis salvage for infections occurring within 28 days depends on the location, extent, and microbiology of the infection [25]. Routine prophylactic use of antibiotic-laden bone cement in primary total knee arthroplasty has not led to changes in infecting pathogen profile or the emergence of antimicrobial resistance at the reporting institution [26].

Outcomes vary by microbiology and treatment strategy. Polymicrobial PJI is associated with a poor outcome compared with monomicrobial and culture-negative infections [13], and these patients are more likely to require a salvage operation [13]. However, polymicrobial prosthetic joint infections have a relatively favorable outcome, especially when treated with two-stage exchange [27]. Salvage of an infection-free prosthetic knee was achieved in only about two thirds of cases following prior staged reimplantation for septic total knee arthroplasty [5]. Survivorship free from persistent PJI at 1 year is 76% in unicompartmental knee arthroplasty treated with DAIR [19]. No substantial improvement in treatment success rates was detected over the 17 years examined [7]. Patients successfully managed for PJI show improvement in generic and joint-specific patient-reported outcome measures compared to their preprimary total joint arthroplasty scores [68]. A review failed to identify a significant difference in the ability of static or articulating spacers to eradicate PJI following total knee arthroplasty [15]. For high-risk candidates, articulating spacers can preserve knee function, reduce morbidity from second-stage surgery, and lower costs with similar rates of infection clearance as two-stage exchange [38]. Patients presenting with PJI from an outside institution were more likely to undergo implant resection compared to those with an index arthroplasty at the investigating institution [72]. The International Consensus on Periprosthetic Joint Infections successfully reached agreement on all but four of 207 questions regarding the prevention, diagnosis, and treatment of PJI [10]. The management of PJI in the future may still be challenging, with numerous problems to resolve and scope for plenty of research [4].

Anatomy & Pathophysiology

Osseous Anatomy

The knee comprises the distal femur, proximal tibia, and patella [40]. The medial femoral condyle is larger and projects farther posteriorly and distally than the lateral condyle [80]. Conversely, the lateral femoral condyle projects farther anteriorly and is wider in the medial-lateral direction [80]. The tibial articular surface slopes 7° to 10° in the sagittal plane [80], with the medial plateau averaging 10.7° and the lateral plateau averaging 7.2° [85]. The medial tibial plateau is larger than the lateral plateau and is concave in both frontal and sagittal planes [80]. The lateral tibial plateau is smaller, more circular, concave in the frontal plane, and convex in the sagittal plane [80]. The patella is the largest sesamoid bone in the body, with a mean thickness of 2.5 cm [80, 85]. Its articular surface features a vertical central ridge separating the broader lateral facet from the medial facet, along with a smaller medial facet known as the odd facet [80].

Ligamentous Anatomy

The anterior cruciate ligament (ACL) travels from the medial border of the lateral femoral condyle to its insertion site anterolateral to the medial tibial spine [40]. It prevents anterior translation and rotation of the tibia on the femur [40]. The ACL is composed of 90% type I collagen and 10% type III collagen [80, 85]. Its mean length is 33 mm and mean midsubstance width is 11 mm [80, 85]. The femoral attachment is a semicircular area on the posteromedial aspect of the lateral femoral condyle [80, 85], while the tibial attachment is a broad, irregular, oval-shaped area between the medial and lateral tibial spinous processes [80, 85].

The posterior cruciate ligament (PCL) runs from the lateral aspect of the medial femoral condyle to the posterior aspect of the tibia, just below the joint line [40]. It prevents posterior subluxation of the tibia on the femur [40]. The PCL is the largest intra-articular ligament, with an average length of 38 mm and a mean midpoint diameter of 13 mm [93]. Its cross-sectional area is approximately 120% to 150% greater than that of the ACL [93]. The PCL consists of an anterolateral (AL) bundle and a posteromedial (PM) bundle defined by femoral insertion [93]. The AL bundle is larger, comprising 85% of the PCL's cross-sectional area [93]. The PCL inserts onto a midline depression on the tibia, 10 to 15 mm below the level of the medial and lateral tibial plateaus [93]. Meniscofemoral ligaments are present in at least one form in 93% of knees [93]. These ligaments connect the posterior horn of the lateral meniscus to the intercondylar notch and contribute to the PCL footprint and cross-sectional area [93].

The medial collateral ligament (MCL) has superficial and deep portions that stabilize the knee to valgus stresses [40]. The lateral collateral ligament runs from the lateral femoral condyle to the head of the fibula and is the main stabilizer against varus stress [40]. The popliteofibular ligament is present in 90% of knees and runs from the tendon of the popliteus muscle to the styloid on the posterior fibular head [40].

Meniscal Anatomy

The menisci are C-shaped fibrocartilaginous disks that provide shock absorption, increase congruency between joint surfaces, enhance joint stability, and aid in distribution of synovial fluid [40]. They are crescent-shaped, fibrocartilaginous structures with a triangular cross section [85]. The medial meniscus is firmly attached to the joint capsule along its entire peripheral edge [40]. It attaches more anterior and posteriorly than the lateral meniscus [85]. The lateral meniscus is attached to the anterior and posterior capsule, but there is a region posterolaterally where it is not firmly attached [40]. The lateral meniscus has a circular shape and covers a larger proportion of the tibial plateau [85].

The medial meniscus has less mobility than the lateral meniscus and is more susceptible to tearing when trapped between the femoral condyle and tibial plateau [40]. The lateral meniscus is larger than the medial meniscus and carries a greater share of the lateral compartment pressure than the medial meniscus carries for the medial compartment [40]. The vascular supply to the menisci is derived from the geniculate arteries, which penetrate into 20% to 30% of the peripheral medial meniscus and 10% to 25% of the peripheral lateral meniscus [85].

Vascular and Neural Anatomy

The blood supply to the knee is formed from an anastomosis around the knee derived from the descending geniculate artery, medial and lateral superior geniculate arteries, medial and lateral inferior geniculate arteries, middle geniculate artery, and anterior tibial recurrent arteries [80]. The middle geniculate artery supplies both the anterior and posterior cruciate ligaments [80]. The popliteus artery travels through the adductor hiatus, where it is relatively immobile, and distally through the fibrous arch deep to the soleus muscle [90].

The knee is innervated by branches of the femoral nerve (L2, L3, L4), obturator nerve (L2, L3, L4), and sciatic nerve (L4, L5, S1, S2) [80]. The posterior articular branch of the tibial nerve is the largest nerve providing innervation of the intra-articular knee [80]. It supplies the infrapatellar fat pad, the synovial covering over the cruciate ligaments, and the periphery of the meniscus [80]. The common peroneal nerve travels along the posterior edge of the biceps femoris and continues distally around the fibular neck [90]. The tibial nerve courses distally through the center of the popliteus fossa after branching from the sciatic nerve [90].

Kinematics and Biomechanics

The knee is a hinge joint that incorporates both gliding and rolling, which are essential to its kinematics [81, 82]. The "screw-home" mechanism involves the tibia externally rotating 5 degrees in the final 15 degrees of extension [81, 82]. The greatest range of motion in the knee occurs in the sagittal plane at approximately 160° [97]. Knee rotation ranges from 45° in external rotation to 30° in internal rotation [97]. The normal instant center of the knee joint follows a semicircular path related to the tibiofemoral surface and ligaments crossing the joint [97]. Rupture of the cruciate ligaments or disruption of the tibiofemoral surface, including the menisci, causes a major change in the path of the instant center, leading to articular dysfunction [97].

In full extension, the knee slightly hyperextends with slight tibial external rotation while collateral and cruciate ligaments are tightened to lock the knee in extension [98]. The popliteus muscle initiates flexion by pulling the lateral femoral condyle backward while the medial femoral condyle slides forward, resulting in tibial internal rotation [98]. The anterior and posterior cruciate ligaments act as the central pivot and gear in the crossed four-bar linkage system of knee motion [98]. The menisci with their capsular attachments provide a peripheral force control and brake system in the crossed four-bar linkage system of knee motion [98].

Pathophysiology of Infection

The risk of periprosthetic joint infection after total joint arthroplasty appears greater in knee arthroplasty compared to hip arthroplasty for patients with a history of treated septic arthritis [1]. Patient factors remain the most important in terms of predicting early prosthetic joint infection following total knee arthroplasty [3, 172]. Greater knee soft tissue thickness predisposes patients to subsequent periprosthetic joint infection after total knee arthroplasty [39]. Soft tissue depth around the knee should be considered in all patients undergoing primary total knee arthroplasty, even in those with lower body mass index [39].

The nature of biofilm varies depending on the type of device and anatomic location [21]. The dynamic life cycle of biofilm necessitates complex interdisciplinary studies [21]. The biofilm paradigm is different from the planktonic paradigm in all of the five H’s (Who, What, When, Where and How) [21]. Polyethylene wear particles initiate an inflammatory process that results in bone resorption and aseptic loosening [97]. Polyethylene debris is phagocytosed by macrophages from the surrounding tissue, inducing these cells to release cytokines that upregulate the production and function of osteoclasts and initiate bone resorption [97].

Synovial fluid analysis is adequate in differentiating patients with periprosthetic hip and knee infections [24]. Neutrophil Extracellular Trap-related biomarkers are increased in the synovial fluid of patients with periprosthetic joint infections [159].

Classification

Periprosthetic joint infections (PJIs) are classified into four types based on duration and the interval from the index procedure [48]. Early postoperative infections present within 4 weeks of the index procedure and are usually seeded intraoperatively, though they can also result from hematogenous spread [48]. Acute hematogenous infections are characterized by an acute presentation in a previously well-functioning joint arthroplasty and may be associated with a documented or suspected bacteremia [48]. Late chronic infections present indolently 1 month or more after the index arthroplasty and are usually low-grade infections thought to originate perioperatively [48]. This category includes missed acute infections (early postoperative or hematogenous) that are now greater than 4 weeks in duration [48]. A final classification group includes patients with positive intraoperative cultures found at the time of revision for presumed aseptic failure [48].

An alternative categorization divides infections into three groups based on timing: early infections (occurring within three months after surgery), delayed infections (appearing between three and 24 months after surgery), and late infections (emerging more than 24 months after surgery) [113].

Staging Systems: A staging system for periprosthetic infections incorporates the infection classification system with the status of the host, including both systemic and local compromising factors [48]. The JS-BACH classification predicts outcome in periprosthetic joint infections based on joint-specific bone involvement, antimicrobial options, coverage of the soft tissues, and host status [142]. The KLIC score (Kidney, Liver, Index surgery and C reactive protein) is a predictor of treatment response in acute prosthetic joint infection and serves as a useful tool in the multidisciplinary treatment of acute prosthetic joint infections in hospitals that are not prosthetic joint infection reference centres [62].

Diagnostic Criteria: The Musculoskeletal Infection Society criteria are used for the diagnosis of periprosthetic joint infection, with major criteria including a communicating sinus tract or two positive cultures with the same organism [140]. These criteria include six minor criteria, where meeting at least four of these is required for diagnosis if major criteria are not met [140].

Other Considerations: The age of the implant is an important predictor of debridement, antibiotics, and implant retention (DAIR) outcomes [141]. DAIR success rates differ based on classification, with 64% success in "early" PJIs (implant <1 year) versus 38% in "late hematogenous" PJIs (implant >1 year) [141]. In late PJIs (implant >1 year), Staphylococcus aureus and gram-negative infections are risk factors for DAIR failure [141]. The time since primary total knee arthroplasty is a key predictor of DAIR success, with success highest in infections occurring within 1 month and progressively decreasing as time since primary increases [28]. Late infections have a high failure rate of DAIR irrespective of their classification as hematogenous or chronic [28]. The prevalence of multiple periprosthetic joint infections has decreased compared with historical reports, likely due to higher rates of 2-stage revisions and fewer patients treated with irrigation and debridement [34]. The pathogen spectra of periprosthetic and native joint infections differ considerably [63].

Clinical Presentation

A history of treated septic arthritis places patients at high risk for periprosthetic joint infection (PJI) following total joint arthroplasty, with this risk appearing greater in knee arthroplasty than in hip arthroplasty [1]. The diagnosis relies on converging information from clinical, laboratory, and imaging assessments, where clinical findings such as a sinus tract serve as major criteria [31]. No single test has demonstrated absolute accuracy; physicians rely on a combination of serological tests, synovial markers, and clinical findings plus clinical judgment to guide preoperative decision-making [53]. Synovial fluid aspiration, diagnostic imaging, traditional culture, peripheral serum inflammatory markers, and intraoperative frozen sections each have limitations but remain the mainstay for diagnosis [59].

Atypical and Late Presentations: Brucella PJI in total knee arthroplasty typically presents late with nonspecific symptoms, often mimicking aseptic loosening or culture-negative PJI [20]. Atypical prosthetic joint infection must be considered in painful total knee arthroplasty with negative cultures and equivocal laboratory results [17]. Approximately 4% of patients with PJI present with normal ESR and CRP [45]. Traditional laboratory markers hold low diagnostic utility for immunosuppressed patients with PJI [16]. D-dimer shows high sensitivity for PJI diagnosis in cases of low-virulence organisms which might be missed by most diagnostic tests [121].

Diagnostic Markers and Limitations: Leukocyte esterase is an accurate and effective synovial fluid marker for diagnosing PJI and should be used in conjunction with the current battery of available diagnostic tests [60]. The specificity of the leukocyte esterase test was found to be 99.3% in a study of 149 patients with degenerative osteoarthritis undergoing total knee arthroplasty [43]. Synovial fluid alpha-defensin can provide an additional data point to assist the clinician in determining whether PJI is present in patients with unclear diagnosis due to recent antibiotic use, equivocal laboratory findings, or suspected false-negative or false-positive cultures, but is prone to false-positive results in this challenging population [117]. Synovial fluid biomarker IL-6 is recommended for the diagnosis of PJI following total hip and knee arthroplasty [56]. Novel microRNA biomarkers offer sensitive and specific pathogen-independent biomarkers with potential clinical applications in the diagnosis of hip and knee PJI [52]. Next-generation sequencing can identify pathogens causing periprosthetic infection in both culture-positive and culture-negative samples of synovial fluid [124]. The accuracy of diagnostic tests for PJI varies with respect to demographic factors, which can help physicians avoid subjecting patients to unnecessary additional testing and reach more accurate diagnoses [55].

Management Implications: Patients with suspected late PJI should not receive antibiotics until the diagnosis is reached or refuted [122]. The AAOS work group recommends against initiating antibiotics before cultures are obtained and against using intraoperative Gram stain to rule out PJI [18]. Polymicrobial PJI is associated with a poor outcome when compared with monomicrobial and culture-negative infections, with patients being more likely to require a salvage operation [13].

Investigations

Diagnostic Criteria and Algorithms

The diagnosis of periprosthetic joint infection relies on converging information from clinical, laboratory, and imaging assessments [31]. No single test has demonstrated absolute accuracy for the diagnosis of periprosthetic joint infection [53]. Consequently, physicians rely on a combination of serological tests, synovial markers, and clinical findings plus clinical judgment to guide preoperative decision-making [53]. A sinus tract serves as a major criterion for the diagnosis of periprosthetic joint infection [31]. The International Consensus on Periprosthetic Joint Infection reached agreement on all but four of 207 questions regarding the prevention, diagnosis, and treatment of periprosthetic joint infection [10]. A validated, evidence-based algorithm for diagnosing periprosthetic joint infection should guide clinicians in the workup of patients undergoing revision arthroplasty [157].

The AAOS work group recommends against initiating antibiotics before cultures are obtained [18]. Additionally, the AAOS work group recommends against using intraoperative Gram stain to rule out periprosthetic joint infection [18].

Laboratory Markers

Leukocyte esterase is an accurate and effective synovial fluid marker for diagnosing periprosthetic joint infection [60]. Leukocyte esterase testing should be used in conjunction with the current battery of available diagnostic tests [60]. Two intra-articular CRP cut-offs have been identified as potentially useful for diagnosing knee prosthesis infection [173]. Synovial fluid microRNA biomarkers offer sensitive and specific pathogen-independent biomarkers with potential clinical applications in the diagnosis of hip and knee periprosthetic joint infection [52].

The routine use of synovial alpha-defensin is not recommended, and it should be reserved for cases where periprosthetic joint infection cannot be diagnosed or ruled out with standard testing [57]. Variation in inflammatory biomarkers among demographic groups significantly affects their accuracy in diagnosing periprosthetic joint infection [55]. The change in serum interleukin-6 between stages does not appear to identify subsequent periprosthetic joint infection in patients undergoing two-stage revision [79].

Further studies are needed to explore diagnostic tests that will better detect periprosthetic joint infection in patients with inflammatory arthritis [167]. Further investigation is necessary to identify the best means of diagnosing periprosthetic joint infection in immunosuppressed patients [16].

Imaging and Other Modalities

CT: CT imaging may help visualize osteolytic lesions around joint arthroplasty and cortical disruption in cases of infection [42].

Bone scan: Gallium-67 radionuclide imaging may help differentiate between aseptic and septic prosthetic loosening [42]. Technetium-99 radionuclide imaging may help identify infection, neoplasia, occult fracture, bone healing, active phases of heterotopic ossification, implant loosening, or failure of osseointegration [42]. Increased radionuclide activity in bone may be a normal postoperative finding for up to 6 to 12 months after a fracture repair or arthroplasty [42].

Other Considerations: Sonication is an evolving modality in the context of periprosthetic joint infections [174]. Further studies are needed to evaluate the role of diagnostic metrics in clinical practice for diagnosing and treating periprosthetic joint infection [170]. More accurate diagnostic tools are needed to support clinical judgment in monitoring infection progress and deciding whether to proceed with total knee arthroplasty reimplantation [171]. Further investigation of diagnostic tests following staged treatment of periprosthetic joint infection is needed [165].

Specific Pathogens and Presentation

Atypical prosthetic joint infection should be considered in painful total knee arthroplasty with negative cultures and equivocal laboratory results [17]. The risk of periprosthetic joint infection appears greater in knee arthroplasty compared to hip arthroplasty for patients with a history of treated septic arthritis [1].

Treatment

General Principles and Guidelines

The International Consensus on Periprosthetic Joint Infections has focused the community and should lead to better research and outcomes [2]. The consensus process successfully reached agreement on all but four of 207 questions regarding the prevention, diagnosis, and treatment of periprosthetic joint infection [10]. Despite increasing clinical focus and research advances, no substantial improvement in treatment success rates for periprosthetic joint infection was detected over the 17 years examined [7]. Periprosthetic joint infection incidence remains stable while mortality remains high [33].

Risk Factors and Patient Selection

Polymicrobial periprosthetic joint infection was associated with a poor outcome when compared with monomicrobial and culture-negative infections, with patients being more likely to require a salvage operation [13]. Orthopaedic surgeons should strongly consider patient comorbidities when selecting treatment pathways for PJIs [149]. A favorable outcome in patients with PJI undergoing 2-stage procedure was associated with an infection sustained by Gram-positive bacteria, absence of known comorbidities, and administration of oral therapy [36]. This study highlights the challenge of treating infected knee arthroplasties in physiologically compromised patients with 9/13 (69%) having satisfactory clinical outcomes [12].

Debridement, Antibiotics, and Implant Retention (DAIR)

Success of prosthesis salvage for periprosthetic infections occurring within 28 days after arthroplasty depends on the location, extent, and microbiology of the infection [25]. DAIR is a viable and safe treatment option for PJI following primary TKA surgery, when performed early after primary surgery and with the addition of a relevant postrevision antibiotic regime [66]. We recommended DAIR as a choice for patients with current infection within 12 weeks after primary TKA [146]. In this study of newly diagnosed PJIs occurring after primary TKA, the time since primary TKA was a key predictor of DAIR success [28]. Success was highest in infections occurring within 1 month and progressively decreased as the time since primary increased [28]. Late infections had a high failure rate of DAIR irrespective of their classification as hematogenous or chronic [28]. The treatment failed to eradicate the infection in 16 cases (84% failure rate), with a total success rate of ODCR in acute periprosthetic MRSA knee infection of 18% when combined with literature review [35]. Given that persistent infection was most common in knees and Staphylococcus aureus, irrigation and debridement should have a limited role in treating periprosthetic joint infection, especially in these cases [61]. I and D was successful in 46 patients (44%) [114]. Patients with staphylococcal infection, elevated American Society of Anesthesiologists score, and purulence around the prosthesis were more likely to fail I and D [114]. The high failure rate of I and D implies that it should be preferably limited to select healthy patients with low virulence organisms and equivocal intraoperative findings [114]. Surgeons should be cautious using irrigation and debridement as a routine means to address periprosthetic joint infection [145]. The probability of treatment failure (removal of implants) was not significantly different among patients treated with single versus multiple I&Ds [54]. The interval between serial I&Ds was a significant factor determining outcomes in patients treated with multiple I&Ds [54]. Patients treated with multiple I&Ds had a significantly higher prevalence of peripheral vascular disease [54]. Survivorship free from persistent PJI at 1 year is low at 76% but is consistent with similar reports of DAIRs for total knee arthroplasties [19].

Two-Stage Revision

Salvage of an infection-free prosthetic knee was achieved in only about two thirds of the cases after prior staged reimplantation [5]. The results support previous studies that demonstrated the effectiveness of a 2-stage reimplantation protocol with a standard 1:8 minimal bactericidal titer for treating infections after TKA, including multidrug-resistant organisms [143]. Prerevision cultures, grown after discontinuation of antibiotic treatment and before reimplantation of the components, helped to identify the patients with infection at the site of a total knee arthroplasty in whom the infection might recur [78]. Outcomes after prosthesis removal and antibiotic spacer placement are variable, and there are several independent risk factors for such outcomes that may be used to develop and improve existing treatment strategies for patients presenting with chronic PJI after TKA [148]. Two-stage exchange arthroplasty was performed in over 75% of the cases in a survey of American Association of Hip and Knee Surgeons members [120]. There was a preference toward performing a two-stage exchange arthroplasty with an articulating spacer using a metal femoral component and an all-polyethylene liner among AAHKS members [120].

One-Stage Revision

Our data provide preliminary support to the use of a single-stage approach in highly selected patients with chronically infected TKAs as an alternative to a two-stage procedure [166]. With an overall revision rate of about 25% at 6 years and limited functional results based on poor Oxford Knee Scores, patients should be counseled to have modest expectations concerning postoperative pain and function for infected rotating-hinge implants treated with one-stage-exchange [29].

Spacers and Antibiotic Delivery

Our review failed to identify a significant difference in the ability of static or articulating spacers to eradicate periprosthetic infection following total knee arthroplasty [15]. Treatment of patients with an infected total knee arthroplasty with high-dose vancomycin and gentamicin antibiotic spacers seems to be clinically safe [127]. Use of an articulating spacer achieved soft tissue compliance, allowed for ease of operation, reduced postoperative pain, improved function, and eradicated infection equal to standards reported in the literature [116]. Routine prophylactic use of antibiotic-laden bone cement in primary total knee arthroplasty has not led to changes in infecting pathogen profile, nor has it led to the emergence of antimicrobial resistance at this institution [26].

Salvage and Alternative Procedures

We describe PJI eradication rate of 72% with acceptable functional outcome for massive endoprostheses used for managing periprosthetic joint infections of the hip and knee [69]. Consistent infection eradication was found at a 1-year follow-up with postoperative range of motion and knee scores comparing favourably with those of other case series for short-interval two-stage approach to primary total knee arthroplasty for acutely septic osteoarthritic knees [22].

Prevention and Prophylaxis

The use of vancomycin as the perioperative prophylactic antibiotic for primary total joint arthroplasties appeared to be effective in decreasing the rate of PJI and may result, when they occur, in infections with less virulent organisms [128]. Administration of intrawound vancomycin powder has no efficacy in preventing periprosthetic joint infection in primary total knee arthroplasty [138]. The trial demonstrated the intrawound application of vancomycin powder to be inferior to standard postoperative IV antibiotics in reducing the incidence of periprosthetic joint infections after total knee arthroplasty [139].

Complications

Infection (PJI): Periprosthetic joint infection (PJI) is a severe complication of total knee arthroplasty that generates high costs for the public health system [23]. The risk of PJI following total joint arthroplasty appears greater in knee arthroplasty compared to hip arthroplasty for patients with a history of treated septic arthritis [1]. Prior cellulitis, especially when occurring within a year of surgery, is a risk factor for PJI after total knee arthroplasty [162]. In patients with multiple arthroplasties, the risk of developing a subsequent PJI was identified to be one half of previous studies [14]. Wound complications after total knee arthroplasty increase cost, length of hospitalization, readmission rates, and the risk of deep infection [70].

Microbiology and Pathogen Characteristics: Polymicrobial prosthetic joint infections represent a substantial proportion of all PJI occurrences [27] and are associated with a poor outcome compared with monomicrobial and culture-negative infections [13]. Concomitant multiple PJIs are rare events that occur most often as a result of secondary hematogenous spread from a distant infectious focus [133]. Atypical prosthetic joint infection, such as that caused by Mycobacterium kansasii, must be considered in painful total knee arthroplasty with negative cultures and equivocal laboratory results [17]. Patients who failed two-stage exchange arthroplasty were 3.37 times more likely to have been originally infected with a methicillin-resistant organism [77].

Treatment Outcomes and Failure Rates: A favorable outcome in patients with PJI undergoing a 2-stage procedure was associated with an infection sustained by Gram-positive bacteria [36], the absence of known comorbidities [36], and the administration of oral therapy [36]. The risk of failure after one-year follow-up is high after revision for periprosthetic joint infection [50]. The high rate of pathogen persistence and the relatively low survival time to recurrence suggests a need to more closely monitor PJI cases within 2 years [74]. Salvage of an infection-free prosthetic knee was achieved in only about two thirds of the cases following prior staged reimplantation for septic total knee arthroplasty [5]. Hematogenous infection after a successful two-stage exchange arthroplasty is a rare but very important cause of reinfection [169]. The prevalence of multiple periprosthetic joint infections has decreased compared with historical reports, likely due to higher rates of 2-stage revisions and fewer patients treated with I&D [34].

Debridement and Implant Retention (DAIR): The treatment failed to eradicate the infection in 16 cases (84% failure rate) for acute methicillin-resistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components [35]. The total success rate of open debridement and component retention in acute periprosthetic MRSA knee infection was 18% when combined with a literature review [35]. Survivorship free from persistent PJI at 1 year is 76% for unicompartmental knee arthroplasty treated with DAIR [19]. The probability of treatment failure (removal of implants) was not significantly different between patients treated with a single I&D and those subjected to additional procedures [54].

Salvage Procedures and Alternative Management: In the unsalvageable, infected total knee arthroplasty, knee arthrodesis is one treatment option with lower reported reinfection rates compared with repeated 2-stage revision [130]. Arthrodesis of the knee using a silver-coated intramedullary device is successful in eradicating infection and allowing limb conservation [130]. Knee arthrodesis provides improved function compared with amputation for the unsalvageable, infected total knee arthroplasty [130]. Periprosthetic joint infection led to a poorer survivorship free of any revision of 70% at 10 years in patients with neuropathic (Charcot) arthropathy [58].

Prophylaxis and Prevention: Routine prophylactic use of antibiotic-laden bone cement in primary total knee arthroplasty has not led to changes in infecting pathogen profile [26] or the emergence of antimicrobial resistance at the reporting institution [26]. Intrawound vancomycin administration does not decrease periprosthetic joint infection occurrence in primary total knee arthroplasty [152] and significantly causes aseptic wound complications [152].

Other Considerations: The International Consensus on Periprosthetic Joint Infections has focused the community and should lead to better research and outcomes, though many areas still require further research [2].

Recovery

Risk Factors and Prognosis: The high rate of pathogen persistence and relatively low survival time to recurrence suggests a need to more closely monitor periprosthetic joint infection cases within 2 years [74]. In patients with neuropathic (Charcot) arthropathy, periprosthetic joint infection led to a 10-year survivorship free of any revision of 70% [58]. Conversely, in patients with asymptomatic elevated inflammatory markers, overall survival was 96.7% at a mean follow-up of 6.4 years, with only 2.2% of patients revised due to a periprosthetic joint infection [65].

Treatment Outcomes and Efficacy: A favorable outcome in patients with periprosthetic joint infection undergoing a 2-stage procedure was associated with an infection sustained by Gram-positive bacteria, absence of known comorbidities, and administration of oral therapy [36]. Survivorship free from persistent periprosthetic joint infection at 1 year is 76% in unicompartmental knee arthroplasty [19]. For massive endoprostheses used for managing periprosthetic joint infections of the hip and knee, an eradication rate of 72% with acceptable functional outcome was described [69].

Surgical Techniques and Devices: For high-risk candidates, articulating spacers can preserve knee function, reduce morbidity from second-stage surgery, and lower the costs with similar rates of infection clearance as 2-stage exchange [38]. Two-stage re-implantation with an articulating spacer for infected total knee arthroplasty effectively treats infection and gives excellent knee motion between stages, and at mid- to long-term follow-up [155]. Consistent infection eradication was found at a 1-year follow-up with a short-interval two-stage approach to primary total knee arthroplasty for acutely septic osteoarthritic knees [22]. Postoperative range of motion and knee scores for the short-interval two-stage approach to primary total knee arthroplasty for acutely septic osteoarthritic knees compare favourably with those of other case series [22]. Rotating hinge total knee arthroplasty using a single modular implant shows acceptable survival rates and function compared to previous studies, with (re-)infection being the most relevant mode of failure [76]. Routine prophylactic use of antibiotic-laden bone cement in primary total knee arthroplasty has not led to changes in infecting pathogen profile at the reporting institution [26].

Monitoring and Diagnostics: Prerevision cultures, grown after discontinuation of antibiotic treatment and before reimplantation of the components, helped to identify patients with infection at the site of a total knee arthroplasty in whom the infection might recur [78]. The change in serum interleukin-6 between stages does not appear to identify subsequent periprosthetic joint infection in patients who have two-stage revision [79]. Brucella periprosthetic joint infections in a total knee arthroplasty typically present late with nonspecific symptoms, often mimicking aseptic loosening or culture-negative periprosthetic joint infections [20].

Compromised Hosts and Special Populations: Treating infected knee arthroplasties in physiologically compromised (host-C) patients presents a challenge, with 9/13 (69%) having satisfactory clinical outcomes [12]. Continued investigation is required to determine the fate of infected joints that undergo debridement, antibiotics, and implant retention (DAIR) with regard to ultimate patient outcome [176].

Key Evidence

• [L3] Patients with a history of treated septic arthritis are at high risk of developing periprosthetic joint infection after total joint arthroplasty, with the risk appearing greater in knee arthroplasty compared to hip arthroplasty. [1] (10.1097/corr.0000000000000734)
• [L5] The International Consensus on Periprosthetic Joint Infections has focused the community and should lead to better research and outcomes, though many areas still require further research. [2] (10.1302/0301-620x.95b11.33224)
• [L2] Patient factors remain the most important in terms of predicting early prosthetic joint infection following total knee arthroplasty. [3] (10.1302/0301-620x.98b3.36775)
• [L5] Despite increasing recent interest, the management of periprosthetic joint infections in the future may still be challenging, with numerous problems to resolve and scope for plenty of research. [4] (10.1302/0301-620x.104b11.bjj-2022-0944)
• [L3] Salvage of an infection-free prosthetic knee was achieved in only about two thirds of the cases. [5] (10.1016/j.arth.2010.04.017)
• [L5] In North America, two-stage revision arthroplasty is the treatment of choice for chronic periprosthetic infection of the hip and knee. [6] (10.5435/jaaos-22-03-153)
• [L3] Despite increasing clinical focus and research advances, no substantial improvement in treatment success rates for periprosthetic joint infection was detected over the 17 years examined. [7] (10.1016/j.arth.2020.01.080)
• [L5] Operative débridement remains the single most important treatment for an infection at the site of a knee prosthesis. [8] (10.2106/00004623-199302000-00018)
• [L2] We recommend that all patients undergoing revision arthroplasty be investigated for periprosthetic joint infection. [9] (10.1016/j.arth.2011.01.019)
• [L5] The consensus process successfully reached agreement on all but four of 207 questions regarding the prevention, diagnosis, and treatment of periprosthetic joint infection, providing a comprehensive approach to minimize variations in care and reduce the burden of infection. [10] (10.1302/0301-620x.95b11.33135)
• [L5] Diagnostic criteria and treatment approaches for periprosthetic joint infection vary globally due to logistical constraints and resource availability, hindering comparative research. [11] (10.2106/jbjs.25.00775)
• [L4] This study highlights the challenge of treating infected knee arthroplasties in physiologically compromised patients with 9/13 (69%) having satisfactory clinical outcomes. [12] (10.1007/s00167-018-5051-y)
• [L3] Polymicrobial periprosthetic joint infection was associated with a poor outcome when compared with monomicrobial and culture-negative infections, with patients being more likely to require a salvage operation. [13] (10.2106/jbjs.15.01450)
• [L3] The study identified the risk of developing a subsequent periprosthetic joint infection to be one half of previous studies. [14] (10.1016/j.arth.2017.10.024)
• [L2] Our review failed to identify a significant difference in the ability of static or articulating spacers to eradicate periprosthetic infection following total knee arthroplasty. [15] (10.2106/jbjs.l.01461)
• [L3] Further investigation is necessary to identify the best means of diagnosing periprosthetic joint infection in this patient population. [16] (10.1016/j.arth.2019.03.013)
• [L5] This case report demonstrates the importance of considering atypical prosthetic joint infection in painful total knee arthroplasty with negative cultures and equivocal laboratory results. [17] (10.5435/jaaosglobal-d-21-00183)
• [L5] The AAOS work group convened to evaluate available evidence for diagnostic modalities and propose an algorithm for diagnosing periprosthetic joint infection (PJI), recommending against initiating antibiotics before cultures are obtained and against using intraoperative Gram stain to rule out PJI. [18] (10.5435/00124635-201012000-00007)
• [L3] Survivorship free from persistent PJI at 1 year is low at 76% but is consistent with similar reports of DAIRs for total knee arthroplasties. [19] (10.1016/j.arth.2020.02.036)
• [L3] Brucella PJIs in a TKA typically present late with nonspecific symptoms, often mimicking aseptic loosening or culture-negative PJIs. [20] (10.2106/jbjs.rvw.25.00079)
• [L5] [21] (10.5435/jaaos-d-14-00455)
• [L5] Consistent infection eradication was found at a 1-year follow-up with postoperative range of motion and knee scores comparing favourably with those of other case series. [22] (10.1007/s00167-016-3982-8)
• [L4] PJIs are a severe complication of total knee arthroplasty that generates a high cost for the public health system. [23] (10.1016/j.arth.2013.02.012)
• [L1] Synovial fluid analysis is adequate in differentiating patients with periprosthetic hip and knee infections. [24] (10.1007/s00264-018-3865-3)
• [L4] Success of prosthesis salvage for periprosthetic infections occurring within 28 days after arthroplasty depends on the location, extent, and microbiology of the infection. [25] (10.1007/s11999-010-1291-y)
• [L3] Routine prophylactic use of antibiotic-laden bone cement in primary total knee arthroplasty has not led to changes in infecting pathogen profile, nor has it led to the emergence of antimicrobial resistance at this institution. [26] (10.1016/j.arth.2013.12.004)
• [L3] Polymicrobial prosthetic joint infections represent a substantial proportion of all PJI occurrences and have a relatively favorable outcome, especially when treated with two-stage exchange. [27] (10.1007/s11999-008-0230-7)
• [L2] [28] (10.1016/j.arth.2023.04.024)
• [L4] With an overall revision rate of about 25% at 6 years and limited functional results based on poor Oxford Knee Scores, patients should be counseled to have modest expectations concerning postoperative pain and function. [29] (10.1097/corr.0000000000001868)
• [L4] The diagnosis of peri-prosthetic bone and joint infections relies on converging information from clinical, laboratory, and imaging assessments, with clinical findings like a sinus tract serving as major criteria. [31] (10.1016/j.otsr.2018.04.029)
• [L5] This editorial summarizes recent literature on musculoskeletal infection, highlighting that periprosthetic joint infection incidence remains stable while mortality remains high, and notes that the efficacy of topical vancomycin and the reliability of certain diagnostic scores remain unresolved or require further validation. [33] (10.2106/jbjs.19.00403)
• [L4] The prevalence of multiple periprosthetic joint infections has decreased compared with historical reports, likely due to higher rates of 2-stage revisions and fewer patients treated with I&D. [34] (10.1016/j.arth.2016.05.013)
• [L3] The treatment failed to eradicate the infection in 16 cases (84% failure rate), with a total success rate of ODCR in acute periprosthetic MRSA knee infection of 18% when combined with literature review. [35] (10.1016/j.arth.2009.04.028)
• [L3] A favorable outcome in patients with PJI undergoing 2-stage procedure was associated with an infection sustained by Gram-positive bacteria, absence of known comorbidities, and administration of oral therapy. [36] (10.1016/j.arth.2017.02.057)
• [L3] For high-risk candidates, articulating spacers can preserve knee function, reduce morbidity from second-stage surgery, and lower the costs with similar rates of infection clearance as 2-stage exchange. [38] (10.1016/j.arth.2023.01.036)
• [L3] Soft tissue depth around the knee should be considered in all patients undergoing primary total knee arthroplasty, even in those with lower body mass index. [39] (10.1016/j.arth.2020.02.049)
• [L3] [43] (10.1016/j.arth.2016.05.065)
• [L3] Approximately 4% of patients with periprosthetic joint infection present with normal ESR and CRP. [45] (10.1302/0301-620x.97b7.35500)
• [L4] [48] (10.1007/s11999-010-1293-9)
• [L3] The risk of failure after one-year follow-up is high after revision for periprosthetic joint infection. [50] (10.1002/ksa.12762)
• [L2] These miRNAs offer sensitive and specific pathogen-independent biomarkers with potential clinical applications in the diagnosis of hip and knee periprosthetic joint infection. [52] (10.2106/jbjs.24.01559)
• [L4] No single test has demonstrated absolute accuracy for the diagnosis of periprosthetic joint infection (PJI); physicians rely on a combination of serological tests, synovial markers, and clinical findings plus clinical judgment to help guide preoperative decision-making. [53] (10.2106/jbjs.23.00669)
• [L3] [54] (10.1016/j.arth.2015.06.051)
• [L3] Understanding how the accuracy of diagnostic tests varies with respect to demographic factors can help physicians avoid subjecting patients to unnecessary additional testing and reach more accurate diagnoses of PJI. [55] (10.1016/j.arth.2020.10.036)
• [L2] On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty. [56] (10.1371/journal.pone.0089045)
• [L2] The authors recommend against its routine use and suggest it be reserved for cases where PJI cannot be diagnosed or ruled out with standard testing. [57] (10.1302/0301-620X.102B5.BJJ-2019-0473.R3)
• [L4] While 10-year survivorship free of aseptic revision was 88%, periprosthetic joint infection led to the poorer survivorship free of any revision of 70% at 10 years. [58] (10.1016/j.arth.2018.04.003)
• [L5] Synovial fluid aspiration, diagnostic imaging, traditional culture, peripheral serum inflammatory markers, and intraoperative frozen sections each have their limitations but continue to be the mainstay for diagnosis of periprosthetic joint infection. [59] (10.5435/jaaos-d-14-00385)
• [L3] LE is an accurate and effective synovial fluid marker for diagnosing periprosthetic joint infection and should be used in conjunction with the current battery of available diagnostic tests. [60] (10.1016/j.arth.2017.06.005)
• [L3] Given that persistent infection was most common in knees and Staphylococcus aureus, irrigation and debridement should have a limited role in treating periprosthetic joint infection, especially in these cases. [61] (10.1016/j.arth.2016.05.040)
• [L3] The KLIC score is a useful tool in the multidisciplinary treatment of acute prosthetic joint infections in hospitals that are not prosthetic joint infection reference centres. [62] (10.1007/s00264-017-3670-4)
• [L3] The pathogen spectra of periprosthetic and native joint infections differ considerably. [63] (10.1186/s13018-021-02850-3)
• [L3] At a mean follow-up of 6.4 years, overall survival was 96.7%, with only 2.2% of patients revised due to a PJI. [65] (10.1016/j.arth.2024.10.063)
• [L3] We find DAIR to be a viable and safe treatment option for PJI following primary TKA surgery, when performed early after primary surgery and with the addition of a relevant postrevision antibiotic regime. [66] (10.1016/j.arth.2018.09.088)
• [L4] Patients who have been successfully managed for PJI show improvement in generic and joint-specific PROMs compared to their preprimary TJA PROMs. [68] (10.1016/j.arth.2025.02.011)
• [L4] We describe PJI eradication rate of 72% with acceptable functional outcome. [69] (10.1016/j.arth.2017.09.046)
• [L5] Wound complications after total knee arthroplasty increase cost, length of hospitalization, readmission rates, and the risk of deep infection; prevention is ideal through optimal patient health, careful planning, and detailed postoperative care. [70] (10.1016/j.arth.2007.03.014)
• [L3] Early-postoperative and late-chronic PJI might require different thresholds. [71] (10.1007/s11999-013-3070-z)
• [L3] Patients presenting with prosthetic joint infection from an outside institution were more likely to undergo implant resection compared to those with an index arthroplasty at the investigating institution. [72] (10.1016/j.arth.2018.09.091)
• [L3] The high rate of pathogen persistence and the relatively low survival time to recurrence suggests a need to more closely monitor PJIs cases within 2 years. [74] (10.1016/j.arth.2023.04.063)
• [L3] Rotating hinge total knee arthroplasty using a single modular implant shows acceptable survival rates and function compared to previous studies with (re-)infection being the most relevant mode of failure. [76] (10.1007/s00167-019-05593-1)
• [L4] Patients who failed two-stage exchange arthroplasty were 3.37 times more likely to have been originally infected with a methicillin-resistant organism. [77] (10.1007/s11999-010-1296-6)
• [L3] Prerevision cultures, grown after discontinuation of antibiotic treatment and before reimplantation of the components, helped to identify the patients with infection at the site of a total knee arthroplasty in whom the infection might recur. [78] (10.2106/00004623-200011000-00006)
• [L3] Furthermore, the change in between stages does not appear to identify subsequent PJI. [79] (10.1016/j.arth.2023.06.008)
• [L1] [113] (10.1016/j.jisako.2023.09.003)
• [L3] [114] (10.1016/j.arth.2010.01.104)
• [L4] [116] (10.1097/01.blo.0000149241.77924.01)
• [L4] In patients for whom the diagnosis of PJI is unclear because of recent antibiotic use, equivocal laboratory findings, or suspected false-negative or false-positive cultures, synovial fluid alpha-defensin can provide an additional data point to assist the clinician in determining whether PJI is present but is prone to false-positive results in this challenging population. [117] (10.1016/j.arth.2018.06.026)
• [L4] [120] (10.1016/j.arth.2023.04.059)
• [L3] However, it shows high sensitivity for PJI diagnosis in cases of low-virulence organisms which might be missed by most diagnostic tests. [121] (10.1016/j.arth.2023.05.022)
• [L3] Patients with suspected late-PJI should not receive antibiotics until the diagnosis is reached or refuted. [122] (10.1007/s11999-015-4142-z)
• [L2] Pathogens causing periprosthetic infection in both culture-positive and culture-negative samples of synovial fluid could be identified by next-generation sequencing. [124] (10.1302/0301-620x.100b2.bjj-2017-0531.r2)
• [L4] Treatment of patients with an infected total knee arthroplasty with high-dose vancomycin and gentamicin antibiotic spacers seems to be clinically safe. [127] (10.1097/01.blo.0000144476.43661.10)
• [L3] The use of vancomycin as the perioperative prophylactic antibiotic for primary total joint arthroplasties appeared to be effective in decreasing the rate of PJI and may result, when they occur, in infections with less virulent organisms. [128] (10.1016/j.arth.2012.03.040)
• [L4] [130] (10.1016/j.arth.2016.04.009)
• [L4] Concomitant multiple PJIs are rare events that occur most often as a result of secondary hematogenous spread from a distant infectious focus. [133] (10.1016/j.arth.2016.02.012)
• [L3] Administration of intrawound vancomycin powder has no efficacy in preventing periprosthetic joint infection in primary total knee arthroplasty. [138] (10.1007/s00167-019-05778-8)
• [L1] The trial demonstrated the intrawound application of vancomycin powder to be inferior to standard postoperative IV antibiotics in reducing the incidence of periprosthetic joint infections after total knee arthroplasty. [139] (10.1016/j.arth.2023.01.040)
• [L4] [140] (10.1016/j.arth.2025.03.005)
• [L3] [141] (10.1016/j.arth.2020.07.081)
• [L2] [142] (10.1016/j.arth.2024.03.070)
• [L3] The results support previous studies that demonstrated the effectiveness of a 2-stage reimplantation protocol with a standard 1:8 minimal bactericidal titer for treating infections after TKA, including multidrug-resistant organisms. [143] (10.1016/j.arth.2009.07.017)
• [L4] Surgeons should be cautious using this procedure as a routine means to address periprosthetic joint infection. [145] (10.1007/s11999-011-1910-2)
• [L3] We recommended DAIR as a choice for patients with current infection within 12 weeks after primary TKA. [146] (10.1186/s13018-022-03218-x)
• [L3] Outcomes after prosthesis removal and antibiotic spacer placement are variable, and there are several independent risk factors for such outcomes that may be used to develop and improve existing treatment strategies for patients presenting with chronic PJI after TKA. [148] (10.1016/j.arth.2017.08.037)
• [L3] Orthopaedic surgeons should strongly consider patient comorbidities when selecting treatment pathways for PJIs. [149] (10.1016/j.arth.2025.05.127)
• [L2] Intrawound vancomycin administration does not decrease periprosthetic joint infection occurrence in primary total knee arthroplasty and significantly causes aseptic wound complications. [152] (10.1007/s00167-019-05498-z)
• [L4] Two-stage re-implantation with an articulating spacer for infected TKA effectively treats infection and gives excellent knee motion between stages, and at mid- to long-term follow-up. [155] (10.1016/j.arth.2008.04.003)
• [L3] This validated, evidence-based algorithm for diagnosing PJI should guide clinicians in the workup of patients undergoing revision arthroplasty and improve clinical practice. [157] (10.1016/j.arth.2019.06.016)
• [Paper] [159] (10.1097/corr.0000000000002971)
• [L3] Prior cellulitis is a risk factor for periprosthetic joint infection after total knee arthroplasty, especially when it occurs within a year of surgery. [162] (10.1016/j.arth.2025.07.007)
• [L3] Further investigation of this and other diagnostic tests following staged treatment of PJI is needed. [165] (10.1016/j.arth.2019.03.019)
• [L3] Our data provide preliminary support to the use of a single-stage approach in highly selected patients with chronically infected TKAs as an alternative to a two-stage procedure. [166] (10.1007/s11999-014-3721-8)
• [L2] Further studies are needed to explore diagnostic tests that will better detect PJI in patients with inflammatory arthritis. [167] (10.1016/j.arth.2019.01.051)
• [L4] Hematogenous infection after a successful two-stage exchange arthroplasty is a rare but very important cause of a reinfection. [169] (10.1007/s00402-018-2972-3)
• [L4] Further studies are needed to evaluate the role of these metrics in clinical practice, whereas the current guidelines provide necessary information for clinicians diagnosing and treating PJI. [170] (10.5435/jaaos-d-20-00438)
• [L3] More accurate diagnostic tools are needed to support clinical judgment in monitoring infection progress and thus deciding whether or not to proceed with TKA reimplantation. [171] (10.1016/j.arth.2008.11.041)
• [L3] Patient factors remain the most important in terms of predicting early PJI following TKA. [172] (10.1177/2325967116s00087)
• [L3] The study identified two intra-articular CRP cut-offs of potential usefulness for diagnosing knee prosthesis infection. [173] (10.1016/j.otsr.2013.10.017)
• [L1] Sonication is an evolving modality in the context of periprosthetic joint infections. [174] (10.1016/j.arth.2018.02.077)
• [L3] Continued investigation is required to determine the fate of infected joints that undergo DAIR with regard to ultimate patient outcome. [176] (10.1097/corr.0000000000003138)

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