Musculoskeletal Infection Society Research Articles

Results of 331 Two-Stage Exchanges for PJI Following THA: Low Reinfection and Mechanical Failure Rates at 10 Years.

The relative advantages and disadvantages of 2-stage versus 1-stage management of infection following total hip arthroplasty (THA) are the current subject of intense debate. To understand the merits of each approach, detailed information on the short and, importantly, longer-term outcomes of each must be known. The purpose of the present study was to assess the long-term results of 2-stage exchange arthroplasty following THA in one of the largest series to date. We identified 331 periprosthetic joint infections (PJIs) that had been treated with a 2-stage exchange arthroplasty between 1993 and 2021 at a single institution. Patients were excluded if they had had prior treatment for infection. The mean age at the time of reimplantation was 66 years, 38% of the patients were female, and the mean body mass index (BMI) was 30 kg/m2. The diagnosis of PJI was based on the 2011 Musculoskeletal Infection Society criteria. A competing-risk model accounting for death was utilized. The mean duration of follow-up was 8 years. The cumulative incidence of reinfection was 7% at 1 year and 11% at 5 and 10 years. Factors predictive of reinfection included BMI ≥30 kg/m2 (hazard ratio [HR] = 2; p = 0.049) and the need for a spacer exchange (HR = 3.2; p = 0.006). The cumulative incidence of any revision was 13% at 5 and 10 years. The cumulative incidence of aseptic revision was 3% at 1 year, 7% at 5 years, and 8% at 10 years. Dislocation occurred in 33 hips (11% at 10 years); 15 (45%) required revision. Factors predictive of dislocation were female sex (HR = 2; p = 0.047) and BMI <30 kg/m2 (HR = 3; p = 0.02). The mean Harris hip score (HHS) improved from 54 to 75 at 10 years. In this series of 331 two-stage exchange arthroplasties that were performed for the treatment of infection, we found a low rate of aseptic revision (8%) and a low rate of reinfection (11%) at 10 years. These long-term mechanical and infection data must be kept in mind when considering a paradigm shift to 1-stage exchanges. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Survivorship of Periprosthetic Joint Infection in Unicompartmental Knee Arthroplasty: A Single Healthcare System's 23-Year Experience.

Unicompartmental knee arthroplasty (UKA) is increasingly favored in clinical practice due to its favorable long-term survival rates, positive clinical outcomes, and expedited recovery. Periprosthetic joint infections (PJIs) remain a formidable complication in knee arthroplasty, and guidelines for the management are limited. This study aims to assess the failure rates of débridement, antibiotics, and implant retention (DAIR) in UKAs, providing insights into optimal treatment management and infection-free survival for PJI in this context. Twenty-five patients met the inclusion criteria of PJI, as defined by Musculoskeletal Infection Society criteria, and were retrospectively reviewed from January 2000 to September 2023. Surgical treatment included 17 DAIRs (78%), six one-stage revision procedures (20%), and three two-stage revision procedures (12%). Seventeen patients (78%) had acute hematogenous infections (<3 weeks of symptoms). Kaplan-Meier survivorship analysis was done for reinfection and revision procedures. The overall infection-free survival and all-cause survival regardless of management at 3 years was 60.1% (95% confidence interval [CI], 45.7% to 89.6%) and 55.8% (95% CI, 38.2% to 81.5%), respectively. Both two-stage and one-stage revision procedures had an infection-free survivorship of 100% at 3 years (95% CI, 100% to 100%). DAIR treatment had an infection-free survival at 3 years of 41.6% (95% CI, 22.4% to 77.4%). Nine of 17 patients (53%) undergoing DAIR were unsuccessful and required subsequent second DAIR, one-stage, or two-stage revision procedures. The efficacy of DAIR following PJI in UKA is notably limited, suggesting a need for reevaluation of its role in managing UKA PJIs. Given the absence of established guidelines for PJI management specifically tailored to UKA, there is an urgent and compelling need for future studies to elucidate optimal clinical strategies to allow for the best treatment for patients. Level III, retrospective comparative study.

A comparison of postoperative microbiological and histological test results with the indication for revision as listed at the time of surgery in the National Joint Registry: a single-centre cohort study of metal-on-metal total hip replacement and hip resurfacing revision procedures.

Surgeons allocate an indication(s) for revision surgery on NJR Minimum Data Set forms in the immediate perioperative period, when results from intraoperative histology and microbiology samples are not available. We evaluated to what extent the postoperative diagnostics obtained for patients undergoing metal-on-metal hip arthroplasty (MoMHA) revision surgery align with the indication for revision listed in the NJR. NJR data for MoMHA revision patients (2004-2015) at a single centre were linked to hospital records of microbiology and histology testing for prosthetic joint infection (PJI) and adverse reaction to metal debris (ARMD). The Musculoskeletal Infection Society and Mirra classifications were used as "gold standards' to classify PJI and ARMD respectively and to assess the diagnostic accuracy of the clinician selected revision indication recorded on MDS forms. Of 301 cases, 5.6% (n = 17) and 3.7% (n = 11) were revised for PJI and ARMD respectively. In a further 6.6% (n = 20, PJI) and 15.6% (n = 47, ARMD) the indication for revision selected at the time of surgery did not corroborate with the test results from intraoperative samples. Diagnostic accuracy analysis revealed sensitivity and specificity of indication for surgery at the time of revision for PJI of 35.5% (95% CI, 19.2-54.6) and 97.8% (CI, 54.6-95.2) respectively, and for ARMD of 7.41% (CI, 2.06-17.9) and 97.2% (CI, 94.3-98.9) respectively. We observed that the results of histology and microbiology analyses of intraoperative samples may provide evidence to support alternative diagnoses in 20% of cases. This indicates a need for a change in the work-up of these cases to allow a more accurate prediction of the indication for revision. Alternatively, if there was evidence of a difference in outcome for patients where the indication may be changed when such data becomes available, the feasibility of a facility to add additional information from samples taken intraoperatively when it becomes available should be explored.

The mononuclear phagocyte system obscures the accurate diagnosis of infected joint replacements

IntroductionDiagnosing infected joint replacements relies heavily on assessing the neutrophil response to bacteria. Bacteria form biofilms on joint replacements. Biofilms are sessile bacterial communities encased in a protective extracellular matrix, making them notoriously difficult to culture, remarkably tolerant to antibiotics, and able to evade phagocytosis. Phagocytized bacteria dramatically alter cytokine production and compromise macrophage antigen presentation. We hypothesize that a subset of joint replacements have a dormant infection that suppresses the neutrophil response to bacteria but can be distinguished from uninfected joint replacements by the response of the mononuclear phagocyte system (MPS) within periarticular tissue, synovial fluid, and circulating plasma.MethodsSingle cell RNASeq transcriptomic and OLink proteomic profiling was performed on matched whole blood, synovial fluid, and periarticular tissue samples collected from 4 joint replacements with an active infection and 3 joint replacements without infection as well as 6 joint replacements with a prior infection deemed “infection-free” by the 2018 Musculoskeletal Infection Society criteria (follow-up of 26 ± 3 months).ResultsThe MPS and neutrophil responses differ by infected state; the cellular distribution of the MPS response in the subset of joints with dormant infections resembled actively infected joints (p = 0.843, Chi-square test) but was significantly different from uninfected joints (p < 0.001, Chi-square test) despite the absence of systemic acute phase reactants and recruitment of neutrophils (p < 0.001, t-test). When compared to no infection, the cellular composition of dormant infection was distinct. There was reduction in classically activated M1 macrophages (p < 0.001, Fischer's test) and alternatively activated M2 macrophages coupled with an increase in classical monocytes (p < 0.001, Fischer’s test), myeloid dendritic cells (p < 0.001, Fischer’s test), regulatory T-cells (p < 0.001, Fischer’s test), natural killer cells (p = 0.009, Fischer’s test), and plasmacytoid dendritic cells (p = 0.005, Fischer’s test). Hierarchical cluster analysis and single-cell gene expression revealed that classically M1 and alternatively M2 activated macrophages as well as myeloid dendritic cells can independently distinguish the dormant and uninfected patient populations suggesting that a process that modulates neutrophil recruitment (C1QA, C1QB, LY86, SELL, CXCL5, CCL20, CD14, ITGAM), macrophage polarization (FOSB, JUN), immune checkpoint regulation (IFITM2, IFITM3, CST7, THBS1), and T-cell response (VISIG4, CD28, FYN, LAT2, FCGR3A, CD52) was occurring during dormant infection. Gene set variation analysis suggested that activation of the TNF (FDR < 0.01) and IL17 (FDR < 0.01) pathways may distinguish dormant infections from the active and uninfected populations, while an inactivation of neutrophil extracellular traps (NETs) may be involved in the lack of a clinical response to a dormant infection using established diagnostic criteria. Synovial inflammatory proteomics show an increase in synovial CXCL5 associated with dormant infection (p = 0.011, t-test), suggesting the establishment of a chronic inflammatory state by the MPS during a dormant infection involved in neutrophil inhibition. Plasma inflammatory proteomics also support a chronic inflammatory state (EGF, GZMN, FGF2, PTN, MMP12) during dormant infection that involves a reduction in neutrophil recruitment (CXCL5, p = 0.006, t-test), antigen presentation (LAMP3, p = 0.047, t-test), and T-cell function (CD28, p = 0.045, t-test; CD70, p = 0.002, t-test) that are also seen during the development of bacterial tolerance.DiscussionAll current diagnostic criteria assume each patient can mount the same neutrophil response to an implant-associated infection. However, the state of the MPS is of critical importance to accurate diagnosis of an implant-associated infection. A reduction in neutrophil recruitment and function mediated by the MPS may allow joint replacements with a dormant infection to be mischaracterized as uninfected, thus limiting the prognostic capabilities of all current diagnostic tests.

Unsuspected Positive Intra-Operative Cultures in Aseptic Revision Hip Arthroplasty: Prevalence, Management, and Infection-Free Survivorship

BackgroundThis study aimed to describe the management and outcomes of aseptic revision total hip arthroplasty (arTHA) with unsuspected intraoperative positive cultures (UPCs) compared to those with sterile cultures. MethodsA single tertiary center’s institutional database was retrospectively reviewed for arTHA from January 2013 to October 2023. Preoperative Musculoskeletal Infection Society scores were assigned to patients based on available infectious workup, and those who met the criteria for periprosthetic joint infection (PJI), received antibiotic spacers, or had less than 1-year follow-up were excluded. Patients were grouped and compared according to intraoperative culture results as follows: sterile cultures, one unexpected positive culture with a new organism, one UPC with the same organism as prior PJI, ≥ two UPCs with different organisms, and ≥ 2 UPCs with the same organism. ResultsThere was a total of 604 arTHAs included in this study, of which 0.8% [5 of 604] had ≥ two UPCs with different organisms, 1.5% [9 of 604] had ≥ two UPCs with the same organism, 9.8% [59 of 604] had one UPC with a new organism, 0.2% [one of 604] had one UPC with an organism from prior PJI, and 87.7% [530 of 604] of patients had sterile cultures. When comparing 5-year infection-free survival between patients who had one UPC with a new organism and sterile cultures, there was no difference (P = 0.40); however, patients who had ≥ two UPCs with different organisms (P < 0.001), patients who had ≥ two UPCs with the same organism (P = 0.001), and patients who had one UPC of an organism from prior PJI (P < 0.001) had statistically worse infection-free survival compared to patients with sterile cultures. ConclusionsInfection-free survival at five years was similar between patients who had one UPC with a new organism and those who had sterile cultures; however, ≥ two UPCs and a history of PJI are both significant risk factors for rerevision for infection after arTHA.

Differences in Success Rate of Two-Stage Revision for Periprosthetic Joint Infection of the Knee Depending on the Applied Definition

BackgroundSuccess rates of two-stage exchange arthroplasty are subject to substantial variance in the literature. An explanation is the lack of a universally accepted definition of what constitutes treatment success for periprosthetic joint infection. Therefore, the main objective of this study was to assess success rates, applying four definitions to identify the one definition that best captures “true” success from both a clinical and patient-centered perspective. MethodsThis was a retrospective study investigating the outcome of a consecutive series of 78 chronic knee periprosthetic joint infections that were treated with a two-stage revision at a single center between 2017 and 2020. Kaplan-Meier survival analyses were conducted to estimate success rates. ResultsAfter a mean follow-up of 36 months (range, 25 to 60), 64 patients (82%) were reimplanted after a mean interim period of 90 days (range, 22 to 201). There was one patient (1%) lost to follow-up, and the overall mortality was 15% (n = 12). Kaplan-Meier survival analyses were used to estimate treatment success at two and three years: implant survival was 93% (95% confidence interval [CI]: 82 to 97) and 87% (95% CI: 73 to 94), infection control was 90% (95% CI: 79 to 95) and 87% (95% CI: 73 to 93), success according to Delphi criteria was 88% (95% CI: 78 to 94), and success according to Musculoskeletal Infection Society criteria was 65% (95% CI: 53 to 74) at both timepoints. ConclusionsSuccess rates were ranging between 65 and 93% depending on the applied definition, highlighting the need for universal success criteria. This variability mainly results from the differing approaches to patients who did not undergo reimplantation or passed away within a year of surgery. These patients exemplify cases of fatal treatment failures. Consequently, the Musculoskeletal Infection Society criteria should be routinely employed to accurately report the “true” success rate.

Prognostic Implications of Unexpected Positive Intraoperative Cultures in Two-Stage Knee Arthroplasty Reimplantations: A Minimum Five-Year Retrospective Analysis

BackgroundThe clinical challenge of unexpected positive intraoperative cultures (UPICs) persists in 2-stage resection arthroplasty for managing periprosthetic joint infections (PJIs) following total knee arthroplasty.(TKA). This study aimed to investigate the incidence of UPICs during the definitive reimplantation phase of 2-stage resection arthroplasty of the knee and to assess both the infection-free and revision-free survivorship of the implanted prosthesis. MethodsThis retrospective study included 450 2-stage resection arthroplasties of primary knee prostheses performed between January 2012 and April 2017. Patients were excluded if they: (1) underwent three or more staged resections, (2) had ambiguous clinical documentation or deviated from the 2-stage protocol, or (3) underwent revision arthroplasty prior to the PJI. Additionally, patients presumed aseptic before the second-stage reimplantation were excluded if they lacked joint aspiration or met the 2011 Musculoskeletal Infection Society criteria for PJI before implantation. ResultsAfter exclusions, 300 patients were analyzed. Among them, 14% had UPIC during the second-stage reimplantation. The follow-up time was 2,316 (range, 1,888 to 3,737) days and 2,531 (range, 1,947 to 3,349) days for UPIC and negative intraoperative culture (NIC) groups, respectively. Rerevision due to subsequent PJI occurred in 26.2% of UPIC patients and 15.1% of NIC patients. The 2-year infection-free survival rates for the NIC, one UPIC, and ≥ two UPIC cohorts were 99.5, 98.2, and 94.3%, respectively, while the 5-year survival rates were 92.1, 91.1, and 54.3%, respectively. The unfavorable survivorship was significantly different in multiple UPIC cases (P < 0.001). Multiple UPICs with pathogens consistent with the first-stage findings were strongly associated with the risk of reinfection (P < 0.001). ConclusionsAn UPIC was identified in 14% of second-stage reimplantations. Patients who had multiple UPICs demonstrated truncated survivorship and suboptimal outcomes relative to the NIC and single UPIC cohorts, especially with pathogen consistency to the first-stage surgery. Level of evidenceIII.

Dual-Energy Computed Tomography Iodine Maps: Application in the Diagnosis of Periprosthetic Joint Infection in Total Hip Arthroplasty

BackgroundThe challenge of early and rapid diagnosis of periprosthetic joint infection (PJI) remains important. This study aimed to assess the efficacy of dual-energy computed tomography (DECT) iodine maps for diagnosing PJI in total hip arthroplasty. MethodsWe prospectively enrolled 68 patients who had postoperative joint pain after hip arthroplasty. All patients underwent preoperative DECT iodine imaging to quantify iodine concentration (IC) in periprosthetic tissues during arterial and venous phases. The diagnostic efficacy of DECT iodine maps was evaluated by constructing receiver operating characteristic curves according to the Musculoskeletal Infection Society criteria. ResultsCompared with erythrocyte sedimentation rate (area under the curve [AUC] = 0.837), polymorphonuclear cell percentage (AUC = 0.703), and C-reactive protein (AUC = 0.837), periprosthetic tissue venous-phase IC (AUC = 0.970) and arterial-phase IC (AUC = 0.964) exhibited outstanding discriminative capability between PJI and aseptic failure. The PJI cut-off point was venous IC = 1.225 mg/mL, with a sensitivity of 92.31% and specificity of 90.48%; for arterial IC = 1.065 mg/mL, the sensitivity was 96.15% and specificity was 90.70%. ConclusionsThis study demonstrates the great potential of DECT iodine maps for the diagnosis of PJI around hip arthroplasty, which helps to differentiate between periprosthetic infection and aseptic failure after hip arthroplasty.

The Effect of Nutritional Status in the Treatment of Periprosthetic Joint Infections in Total Hip Arthroplasty

BackgroundPeriprosthetic joint infections (PJIs) continue to be a complication that plagues arthroplasty. Albumin is a surrogate marker for nutrition as well as chronic inflammation, and hypoalbuminemia increases the risk of complications in arthroplasty. Patients with PJI are at increased risk for malnutrition and complications. This study’s objective was to analyze patients who underwent treatment of PJI following total hip arthroplasty and investigate the outcome with regards to albumin levels. MethodsOverall, 48 patients who underwent surgery for a total hip PJI at 1 institution were reviewed. Albumin and C-reactive protein were recorded preoperatively and 2 to 3 weeks postoperatively. Treatment failure was determined by further surgical treatment for PJI or repeat infection, as determined by Musculoskeletal Infection Society guidelines. ResultsA debridement, antibiotics, and implant retention procedure was performed in 39 patients, and explant with the placement of an antibiotic spacer was performed in 9. Preoperative mean albumin levels were significantly decreased in patients who failed to clear their infection compared to patients who remained infection-free (2.5 versus 3.3, P < .001). Postoperative albumin levels decreased in this same population (2.6 versus 3.8, P < .001). C-reactive protein was elevated in patients who failed to clear their infection preoperatively (19.9 versus 7.5, P < .001) and postoperatively (7.0 versus 1.7, P < .001). The average time to repeat surgical treatment for their PJI was 9 months ConclusionsLower albumin levels are observed in patients with PJI who failed to remain infection-free after surgery. Albumin is a surrogate marker for nutrition, and low albumin is associated with poor immune function. Hypoalbuminemia is found with chronic inflammation as well as malnutrition. Nutritional reserves are diverted to the acute inflammatory response during an infection, which can lead to a deficient state. Further research may develop treatments to alter this modifiable risk factor. Level of EvidenceLevel 4.

Comparison of the effect of combined usage of povidone-iodine irrigation and topical vancomycin powder to the use of povidone-iodine irrigation alone on the periprosthetic joint infection incidence rate in patients undergoing primary total hip and knee arthroplasty: a protocol for multicenter prospective randomized clinical trial

BackgroundWith the increasing number of joint replacement surgeries, periprosthetic joint infection (PJI) has become a significant concern in orthopedic practice, making research on PJI prevention paramount. Therefore, the study will aim to compare the effect of combined usage of povidone-iodine and topical vancomycin powder to the use of povidone-iodine alone on the PJI incidence rate in patients undergoing primary total hip (THA) and total knee arthroplasty (TKA).MethodsThe prospective randomized clinical trial will be conducted in two independent voivodeship hospitals with extensive experience in lower limb arthroplasties. The studied material will comprise 840 patients referred to hospitals for primary THA or TKA. The patients will be randomly allocated to two equal groups, receiving two different interventions during joint replacement. In group I, povidone-iodine irrigation and consecutively topical vancomycin powder will be used before wound closure. In group II, only povidone-iodine lavage irrigation will be used before wound closure. The primary outcome will be the incidence rate of PJI based on the number of patients with PJI occurrence within 90 days after arthroplasty. The occurrence will be determined using a combined approach, including reviewing hospital records for readmissions and follow-up phone interviews with patients. The infection will be diagnosed based on Musculoskeletal Infection Society criteria. The chi-square test will be used to compare the infection rates between the two studied groups. Risk and odds ratios for the between-groups comparison purposes will also be estimated. Medical cost analysis will also be performed.DiscussionA randomized clinical trial comparing the effect of combined usage of povidone-iodine irrigation and vancomycin powder to the use of povidone-iodine irrigation alone in preventing PJIs after primary arthroplasty is crucial to advancing knowledge in orthopedic surgery, improving patient outcomes, and guiding evidence-based clinical practices.Trial registrationClinicalTrials.gov NCT05972603. Registered on 2 August 2023.

Can Periprosthetic Joint Infection of Tumor Prostheses Be Controlled With Debridement, Antibiotics, and Implant Retention?

Two-stage revision for periprosthetic joint infection (PJI) in patients who have undergone segmental replacement of the distal femur or proximal tibia after tumor resection can be associated with considerable morbidity, pain, and risk of complications because the procedure often results in removal of long, well-fixed stems from the diaphysis. A less-aggressive surgical approach, such as debridement, antibiotics, and implant retention (DAIR), may be attractive to patients and surgeons because of less morbidity, but the likelihood of eradicating infection in comparison to the traditional two-stage revision is not well established for oncology patients. Furthermore, the relative risk of subsequent amputation for DAIR versus two-stage revision has not been defined for this population. (1) How does DAIR compare with two-stage revision in terms of infection control for patients with distal femoral or proximal tibial segmental modular endoprostheses? (2) Is DAIR as an initial procedure associated with an increased risk of amputation compared with two-stage revision for infection? From the longitudinally maintained orthopaedic oncology surgical database at our institution, we identified 69 patients who had been treated for a clinical diagnosis of PJI at the knee between 1993 and 2015. We excluded 32% (22) of patients who did not meet at least one of the major criteria of the Musculoskeletal Infection Society (MSIS) for PJI, 3% (2) of patients who underwent immediate amputation, 3% (2) of patients who had a follow-up time of < 24 months, and 7% (5) of patients who did not have a primary tumor of the distal femur or proximal tibia. The study consisted of 38 patients, of whom eight underwent two-stage revision, 26 underwent DAIR, and four underwent extended DAIR (removal of all segmental components but with retention of stems and components fixed in bone) for their initial surgical procedure. To be considered free of infection, patients had to meet MSIS standards, including no positive cultures, drainage, or surgical debridement for a minimum of 2 years from the last operation. Factors associated with time-dependent risk of infection relapse, clearance, amputation, and patient survival were analyzed using Kaplan-Meier survivorship curves and the log-rank test to compare factors. Association of demographic and treatment factors was assessed using chi-square and Fisher exact tests. Continuous infection-free survival at 5 years was 16% (95% CI 2% to 29%) for patients undergoing DAIR compared with 75% (95% CI 45% to 100%) for patients undergoing two-stage revision (p = 0.006). The median (range) number of total surgical procedures was 3 per patient (1 to 10) for DAIR and 2 (2 to 5) for two-stage revision. Twenty-nine percent (11 of 38) of patients eventually underwent amputation. Survival without amputation was 69% (95% CI 51% to 86%) for DAIR compared with 88% (95% CI 65% to 100%) for two-stage revision at 5 years (p = 0.34). The cumulative proportion of patients achieving infection-free status (> 2 years continuously after last treatment) and limb preservation was 58% (95% CI 36% to 80%) for patients initially treated with DAIR versus 87% (95% CI 65% to 100%) for patients first treated with two-stage revision (p = 0.001). Infection control was better with two-stage revision than DAIR. The chance of eventual clearance of infection with limb preservation was better when two-stage revision was chosen as the initial treatment. However, the loss to follow-up in the two-stage revision group would likely make the true proportion of infection control lower than our estimate. Our experience would suggest that the process of infection eradication is a complex and difficult one. Most patients undergo multiple operations. Nearly one-third of patients eventually underwent amputation, and this was a serious risk for both groups. While we cannot strongly recommend one approach over the other based on our data, we would still consider the use of DAIR in patients who present with acute short duration of symptoms (< 3 weeks), no radiographic signs of erosion around fixed implants, and organisms other than Staphylococcus aureus. We would advocate the extended DAIR procedure with removal of all segmental or modular components, and we would caution patients that there is a high likelihood of needing further surgery. A prospective trial with strict adherence to indications may be needed to evaluate the relative merits of an extended DAIR procedure versus a two-stage revision. Level III, therapeutic study.

The Impact of Culture Negativity on the Outcomes of Revision Total Knee Arthroplasty for Chronic PJI.

Culture-positive (CP) and culture-negative (CN) periprosthetic joint infections (PJI) remain a crucial area of research; however, current studies comparing these infections rely on unstandardized outcome reporting tools. Our study aimed to compare the outcomes of two-stage revision of CP and CN PJI using the standardized Musculoskeletal Infection Society (MSIS) outcome reporting tool. We retrospectively reviewed 138 patients who were diagnosed with PJI and indicated for two-stage revision total knee arthroplasty (rTKA). The majority of patients in both CP and CN cohorts achieved infection control without the need for reoperation (54.1% and 62.5%, respectively). There was a significant difference in the overall distribution of MSIS outcomes (p = 0.043), with a significantly greater rate of CN patients falling into Tier 1 (infection control without the use of suppressive antibiotics) (52.5% versus 29.6%, p = 0.011). There was also a significant difference in the distribution of septic versus aseptic reoperations after 2nd stage (p = 0.013), with more CP reoperations being septic and more CN reoperations being aseptic. The duration from first to second stage was significantly shorter in the CN cohort (p = 0.002). While overall infection control was similar between cohorts, these data suggest that the outcomes of two-stage rTKA are favorable in cases of CN PJI.

Periprosthetic Joint Infections of the Knee-Comparison of Different Treatment Algorithms.

Background: Periprosthetic joint infection (PJI) following total knee arthroplasty is a serious complication lacking evidence-based diagnostic and treatment protocols, particularly in ruling out persisting infection before reimplantation. Methods: This retrospective analysis assessed the mid-term outcomes of 66 patients undergoing septic two-stage knee revision surgeries from 2007 to 2013, diagnosed as per the Musculoskeletal Infection Society criteria. After implant removal and antibiotic treatment, reimplantation decisions were based on either joint aspiration, blood counts, and clinical examination (group A) or an open biopsy (group B). Both groups underwent meticulous debridement and spacer exchange during the interim period. Results: Late re-infection occurred in 12.1% of all patients. In group A, 13.8% experienced late re-infection, with 14.3% in subgroup A1 and 13.3% in subgroup A2. In group B, 10% had a late re-infection. No significant difference in re-infection or complication rates was found between the groups. Conclusions: The study did not demonstrate the superiority of group B's approach of open biopsy over group A's joint aspiration, clinical examination, and blood counts in preventing re-infection or reducing complications.

Unsuspected Positive Intraoperative Cultures in Aseptic Revision Knee Arthroplasty: Prevalence, Management, and Infection-Free Survivorship

BackgroundThe purpose of this study was to evaluate the management and outcomes of aseptic revision total knee arthroplasty (arTKA) with unsuspected positive cultures (UPCs) compared to those with sterile cultures. MethodsThe institutional database at a single tertiary center was retrospectively reviewed for arTKA from January 2013 to October 2023. Patients who met Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) based on available preoperative infectious workup, received antibiotic spacers, or did not have at least 1 year of follow-up were excluded. Patients were stratified based on intraoperative cultures into 4 cohorts: sterile cultures, 1 UPC, ≥ 2 UPCs with different organisms, and ≥ 2 UPCs with the same organism. Univariable analyses were used to compare these groups. Kaplan-Meier survivorship analysis assessed infection-free survival at 5 years, and Cox proportional hazards regressions were used to evaluate factors that influence infection-free survival. A total of 691 arTKAs at a mean follow-up of 4.2 years were included in the study. Of these, 49 (7.1%) had 1 UPC with a new organism, 10 (1.4%) had ≥2 UPCs of the same organism, and 2 (0.2%) had ≥2 UPCs with different organisms. ResultsPostoperative antibiotics were prescribed to 114 (16.5%) patients—13 (26.5%) with 1 UPC, 6 (60.0%) with ≥2 UPCs of the same organism, and 0 (0.0%) of patients who had ≥2 UPCs of different organisms. There were no differences in infection-free survival at 5 years between patients who had sterile cultures and 1 UPC (96 versus 89%; P = .39) nor between sterile cultures and ≥2 UPCs of different organisms (96 versus 100%; P < .72). However, patients who had ≥2 UPCs of the same organism had significantly worse infection-free survival at 5 years compared to patients who had sterile cultures (58 versus 96%; P < .001). Cox proportional hazards regression suggested that when adjusting for covariates, an American Society of Anesthesiologists classification of ≥3 (hazard ratio [HR] = 3.1; P = .007), ≥2 UPCs of the same organism (HR = 11.0; P < .001), 1 UPC (HR = 4.2; P = .018), and arTKA with hinge constructs (HR = 4.1; P = .008) were associated with increased risk of rerevision for PJI. ConclusionsPatients who had 1 UPC or ≥2 UPCs with different organisms had similar infection-free survival at 5 years as patients who had sterile cultures. However, patients who had ≥2 UPCs of the same organism had significantly worse infection-free survival at 5 years. Overall, 1 UPC or ≥2 UPCs of the same organism at the time of arTKA may suggest the patient is at higher risk of rerevision for PJI. More studies are needed to determine what interventions can be implemented to mitigate this risk.

Comparable Results of Single and Two-Stage Exchange for Select Periprosthetic Hip and Knee Infection.

Although two-stage exchange has been the standard of care for periprosthetic joint infection (PJI) in the United States, single-stage exchange is emerging as an option in select patients. The purpose of this study was to compare outcomes of patients undergoing single-stage and two-stage exchange using strict surgical indications. We reviewed a consecutive series of 196 patients with diagnosed PJI undergoing revision total knee and hip arthroplasty from 2017 to 2021. Patients were excluded if they had PJI history, plastic surgery coverage, or extensive bone loss requiring endoprosthesis. We compared the number of patients PJI-free at 1-year follow-up using MusculoSkeletal Infection Society criteria and patients requiring re-revision between the single-stage and two-stage groups. In total, 126 patients met inclusion criteria. Of 61 knee patients (48.4%), 22 underwent single-stage (36%) and 39 underwent two-stage (63.9%). Of 65 hip patients (51.6%), 38 underwent single-stage (58.5%) and 27 underwent two-stage (41.5%). At a mean follow-up of 1.95 ± 0.88 years, a higher rate of knee patients were classified as having treatment success in the single-stage group (77.3% versus 69.2%, P = 0.501), however with comparable septic failure rates (18.1% single-stage versus 17.9% two-stage; P = 0.982). At a mean follow-up of 1.81 ± 0.9 years, a higher rate of hip patients were classified as having treatment success in the single-stage group (94.7% versus 81.5%, P = 0.089), and more patients had septic failures in the two-stage group (18.5% versus 5.3%; P = 0.089). No differences were observed in the microorganism profile. More total complications ( P = 0.021) and mortalities were found in the single-stage knee cohort than in the two-stage cohort (22.7% versus 2.6%; P = 0.011). Single-stage arthroplasty is a viable alternative to standard two-stage exchange in patients with PJI without a history of infection and with no bone or soft-tissue compromise. Additional studies with longer term follow-up are needed to evaluate its efficacy.

The James A. Rand Young Investigator’s Award: Keeping It Simple: Are all Musculoskeletal Infection Society Tests Useful to Diagnose Periprosthetic Joint Infection?

BackgroundCurrent data evaluating the clinical value and cost-effectiveness of advanced diagnostic tests for periprosthetic joint infection (PJI) diagnosis, including alpha-defensin and synovial C-reactive protein (CRP), is conflicting. This study aimed to evaluate the adequacy of preoperative and intraoperative PJI workups without utilizing these tests. MethodsThis retrospective analysis identified all patients who underwent revision total knee or hip arthroplasty (rTKA and rTHA, respectively) for suspected PJI between 2018 and 2020 and had a minimum follow-up of 2 years. Perioperative data and lab results were collected, and cases were dichotomized based on whether they met the 2018 Musculoskeletal Infection Society (MSIS) criteria for PJI. In total, 204 rTKA and 158 rTHA cases suspected of PJI were reviewed. ResultsNearly 100% of the cases were categorized as “infected” for meeting the 2018 MSIS criteria without utilization of alpha-defensin or synovial CRP (rTKA: n = 193, 94.6%; rTHA: n = 156, 98.7%). Most cases were classified as PJI preoperatively by meeting either the major MSIS or the combinational minor MSIS criteria of traditional lab tests (rTKA: n = 177, 86.8%; rTHA: n = 143, 90.5%). A subset of cases was classified as PJI by meeting combinational preoperative and intraoperative MSIS criteria (rTKA: 16, 7.8%; rTHA: 13, 8.2%). Only 3.6% of all cases were considered “inconclusive” using preoperative and intraoperative data. ConclusionsGiven the high rate of cases satisfying PJI criteria during preoperative workup using our available tests, the synovial alpha-defensin and synovial CRP tests may not be necessary in the routine diagnostic workup of PJI. We suggest that the primary PJI workup process should be based on a stepwise algorithmic approach with the most economical testing necessary to determine a diagnosis first. The use of advanced, commercialized, and costly biomarkers should be utilized only when traditional testing is indeterminate.

Perioperative Demographic and Laboratory Characteristics of Failed Debridement, Antibiotics, and Implant Retention: Can We Determine Which Patients Will Fail?

BackgroundDebridement, antibiotics, and implant retention (DAIR) are the mainstays surgical treatment for acute periprosthetic joint infection (PJI). However, reoperation following DAIR is common and the risk factors for DAIR failure remain unclear. This study aimed to assess the perioperative characteristics of patients who failed initial DAIR treatment. MethodsA retrospective review was conducted on 83 patients who underwent DAIR for acute PJI within 3 months following index surgery from 2011 to 2022, with a minimum one-year follow-up. Surgical outcomes were categorized using the Musculoskeletal Infection Society outcome reporting tool (Tiers 1 to 4). Patient demographics, laboratory data, and perioperative outcomes were compared between patients who had failed (Tiers 3 and 4) (n = 32) and successful (Tiers 1 and 2) (n = 51) DAIR treatment. Logistic regression was also performed. ResultsAfter logistic regression, Charlson Comorbidity Index (odds ratio [OR]: 1.57; P = .003), preoperative C-reactive protein (OR: 1.06; P = .014), synovial white blood cell (OR: 1.14; P = .008), and polymorphonuclear cell (PMN%) counts (OR: 1.05; P = .015) were independently associated with failed DAIR. Compared with total hip arthroplasty, total knee arthroplasty patients (OR: 6.08; P = .001) were at increased risk of DAIR failure. The type of organism and time from primary surgery were not correlated with DAIR failure. ConclusionsPatients who had failed initial DAIR tended to have significantly higher Charlson Comorbidity Index, C-reactive protein, synovial white blood cell, and PMN%. The total knee arthroplasty DAIRs were more likely to fail than the total hip arthroplasty DAIRs. These characteristics should be considered when planning acute PJI management, as certain patients may be at higher risk for DAIR failure and may benefit from other surgical treatments. Level of EvidenceIII.

Evaluating Modern Spacer Options and Outcomes in Revision Hip Arthroplasty

BackgroundA 2-stage revision continues to be the standard treatment for periprosthetic joint infection (PJI) in hip arthroplasty. The use of “functional” spacers may allow patients to return to daily living while optimizing their health for revision surgery. We aimed to evaluate the clinical outcomes of different spacer types regarding infection eradication, mechanical complications, and functional outcomes. MethodsPatients who have complete Musculoskeletal Infection Society criteria for diagnosis of PJI that underwent one-stage or 2-stage revision were queried in an institutional surgical database between 2002 and 2022. Out of 286 patients, 210 met our inclusion criteria and were retrospectively reviewed for demographics, laboratory values, functional and patient-reported outcomes, and subsequent revisions. The study population had 54.3% women, a mean age of 61 years old, and a mean follow-up of 3.7 ± 3.2 years. There was no difference between age, body mass index, or Charlson Comorbidity Index scores between each cohort. Spacers were categorized as nonfunctional static, nonfunctional articulating, or functional articulating. Functional spacers were defined as those that allowed full weight bearing with no restrictions. Delphi criteria were used to define revision success, and failure was defined as a recurrent or persistent infection following definitive surgery. ResultsThere was a significantly lower reoperation rate after a definitive implant in the functional articulating cohort (P = .003), with a trending higher infection eradication rate and a lower rate of spacer failure compared to the nonfunctional spacer cohort. At 5 years, functional articulating spacers had a 94.1% survivorship rate, nonfunctional articulating spacers had an 81.2% survival rate, and nonfunctional static spacers had a 71.4% survival rate. In the functional articulating spacer cohort, 14.6% had yet to get reimplanted, with an average follow-up time of 1.4 years. ConclusionsWithin this large cohort of similar demographics, functional articulating spacers may result in better clinical outcomes and infection eradication during 2-stage revision arthroplasty for PJI.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study

BackgroundPeriprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsWe performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated.ResultsCompared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688–0.823), 0.758 (95% CI: 0.687–0.821), 0.714 (95% CI: 0.639–0.781), 0.709 (95% CI: 0.634–0.777), 0.723 (95% CI: 0.649–0.789), and 0.728 (95% CI: 0.654–0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499–0.653) and 0.694 (95% CI: 0.619–0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790–0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015).ConclusionOur study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Changing the definition of treatment success alters treatment outcomes in periprosthetic joint infection: a systematic review and meta-analysis.

Background: Variability in the definition of treatment success poses difficulty when assessing the reported efficacy of treatments for hip and knee periprosthetic joint infection (PJI). To address this problem, we determined how definitions of PJI treatment success have changed over time and how this has affected published rates of success after one-stage and two-stage treatments for hip and knee PJI. Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify one-stage and two-stage revision hip and knee PJI publications in major databases (2006-2021). Definition of treatment success, based on Musculoskeletal Infection Society tier criteria, was identified for each study. Publication year, number of patients, minimum follow-up, and study quality were also recorded. The association of success definitions and treatment success rate was measured using multi-variable meta-regression. Results: Study quality remained unchanged in the 245 publications included. Over time, no antibiotics (tier 1) and no further surgery (tier 3) (40.7 % and 54.5 %, respectively) became the two dominant criteria. After controlling for type of surgery, study quality, study design, follow-up, and year of publication, studies with less strict success definitions (tier 3) reported slightly higher odds ratios of 1.05 [1.01, 1.10] ( ) in terms of treatment success rates compared to tier 1. Conclusions: PJI researchers have gravitated towards tier-1 and tier-3 definitions of treatment success. While studies with stricter definitions had lower PJI treatment success, the clinical significance of this is unclear. Study quality, reflected in the methodological index for non-randomized studies (MINORS) score, did not improve. We advocate for improving PJI study quality, including clarification of the definition of treatment success.