Treatment Outcomes and Attrition in Gram-Negative Periprosthetic Joint Infection

BackgroundWhile the prevailing belief is that periprosthetic joint infection (PJI) caused by Gram-negative (GN) organisms confers a poorer prognosis than Gram-positive (GP) cases, the current literature is sparse and inconsistent. The purpose of this study is to compare the treatment outcomes for GN PJI vs GP PJI and Gram-mixed (GM) PJI.MethodsA retrospective review of 1189 PJI cases between 2007 and 2017 was performed using our institutional PJI database. Treatment failure defined by international consensus criteria was compared between PJI caused by GN organisms (n = 45), GP organisms (n = 663), and GM (n = 28) cases. Multivariate regression was used to predict time to failure.ResultsGM status, but not GN, had significantly higher rates of treatment failure compared to GP PJI (67.9% vs 33.2% failure; hazards ratio [HR] = 2.243, P = .004) in the multivariate analysis. In a subanalysis of only the 2-stage exchange procedures, both GN and GM cases were significantly less likely to reach reimplantation than GP cases (HR = .344, P < .0001; HR = .404, P = .013).ConclusionAlthough there was no observed difference in the overall international consensus failure rates between GN (31.1% failure) and GP (33.2%) PJI cases, there was significant attrition in the 2-stage exchange GN cohort, and these patients were significantly less likely to reach reimplantation. Our findings corroborate the prevailing notion that GN PJI is associated with poorer overall outcomes vs GP PJI. These data add to the current body of literature, which may currently underestimate the overall failure rates of GN PJI treated via 2-stage exchange and fail to identify pre-reimplantation morbidity.     

Defining Treatment Success After 2-Stage Exchange Arthroplasty for Periprosthetic Joint Infection

Background

Two-stage exchange arthroplasty remains the preferred surgical treatment method for patients with chronic periprosthetic joint infection (PJI). The success of this procedure is not known exactly as various definitions of success have been used. This study aimed at analyzing the difference in outcome following 2-stage exchange arthroplasty using different definitions for success.

Differences in Diagnostic Properties Between Standard and Enrichment Culture Techniques Used in Periprosthetic Joint Infections

BackgroundCulture-negative infections can complicate the diagnosis and management of orthopedic infections, particularly periprosthetic joint infections (PJIs). This study aimed to identify differences in rate of detection of infection and organisms between cultured using standard and enriched methods.MethodsThis retrospective, cross-sectional study evaluated PJI samples obtained between January 2013 and December 2017 at Yokohama City University Hospital. Samples were assessed using standard and enrichment culture techniques. White blood cell counts, C-reactive protein levels, type of microorganism (coagulase-positive or coagulase-negative), and methicillin-resistant Staphylococcus were investigated.ResultsA total of 151 PJI samples were included in the analysis; of these, 68 (45.0%) were positive after standard culture while 83 (55.0%) were positive only after enrichment culture. The mean white blood cell counts and C-reactive protein levels were significantly lower in the enrichment culture group than in the standard culture group (P < .01). The rate of methicillin-resistant Staphylococcus and coagulase-negative Staphylococci was significantly higher in the enrichment culture group than in the standard culture group (P < .01).ConclusionThe enrichment culture method has a higher rate of detection of infection than standard culture techniques and should, therefore, be considered when diagnosing orthopedic infections, particularly PJI.     

Treatment and Outcome of Periprosthetic Joint Infection in Unicompartmental Knee Arthroplasty

BackgroundPeriprosthetic joint infection (PJI) after unicompartmental knee arthroplasty (UKA) is a devastating but poorly understood complication, with a paucity of published data regarding treatment and outcomes. This study analyzes the largest cohort of UKA PJIs to date comparing treatment outcome, septic and aseptic reoperation rates, and risk factors for treatment failure.MethodsTwenty-one UKAs in 21 patients treated for PJI, as defined by Musculoskeletal Infection Society criteria, were retrospectively reviewed. Minimum and mean follow-up was 1 and 3.5 years, respectively. Fourteen (67%) patients had acute postoperative PJIs. Surgical treatment included 16 debridement, antibiotics, and implant retentions (DAIRs) (76%), 4 two-stage revisions (19%), and 1 one-stage revision (5%). Twenty (95%) PJIs were culture positive with Staphylococcus species identified in 15 cases (71%).ResultsSurvivorship free from reoperation for infection at 1 year was 76% (95% confidence interval, 58%-93%). Overall survival from all-cause reoperation was 57% (95% confidence interval, 27%-87%) at 5 years. Two additional patients (10%) underwent aseptic revision total knee arthroplasty for lateral compartment degeneration 1 year after DAIR and tibial aseptic loosening 2.5 years after 2-stage revision. All patients who initially failed PJI UKA treatment presented with acute postoperative PJIs (5 of 14; 36%).ConclusionSurvivorship free from persistent PJI at 1 year is low at 76% but is consistent with similar reports of DAIRs for total knee arthroplasties. Furthermore, there is low survivorship free from all-cause reoperation of 71% and 57% at 2 and 5 years, respectively. Surgeons should be aware of these poorer outcomes and consider treating UKA PJI early and aggressively.     

Interim Spacer Exchange for Treatment of Periprosthetic Joint Infection: Almost Half the Patients Subsequently Fail

BackgroundInterim spacer exchange may be performed in patients undergoing 2-stage exchange for periprosthetic joint infection. Several studies have demonstrated that interim spacer exchange is associated with poor outcomes. This study investigated the survivorship and risk factors for failure in patients with an interim spacer exchange.MethodsTwo institutional databases identified 182 patients who underwent spacer exchange from 2000 to 2017. Primary outcomes included progression to reimplantation, treatment success, and mortality. Bivariate analysis was performed to evaluate risk factors associated with failure. Kaplan-Meier curves using host and local grades were generated to evaluate for primary outcomes and differences in survivorship.ResultsThe overall failure rate was 49% in patients with a spacer exchange. Most patients (60%) failed before 2 years. Higher comorbidity scores, elevated erythrocyte sedimentation rate, and non-White race were more prevalent in patients who failed. Negative cultures at the time of exchange were more prevalent in patients who did not fail. Failure rate was higher in immunocompromised conditions, and those who had revision prior to exchange. After considering clinically relevant variables, advanced host grade C was the single factor associated with treatment failure. Although survivorship curves were not significantly different between extremity local grades, higher host grades were associated with treatment failure.ConclusionAlmost 1 out of 2 patients with spacer exchange were found to fail the intended 2-stage revision arthroplasty. Benefits of delivering additional antibiotic load with a new spacer should be balanced against poor outcomes in patients with the aforementioned risk factors.     

Risk of Periprosthetic Joint Infection After Intra-Articular Corticosteroid Injection Following Unicompartmental Knee Arthroplasty

BackgroundPerioperative intra-articular joint injection is a known risk factor for developing prosthetic joint infection (PJI) in the immediate preoperative and postoperative periods for total knee arthroplasty, but is less defined in unicompartmental knee arthroplasty (UKA). The goal of this study was to elucidate the risk of developing PJI after intra-articular corticosteroid injection (IACI) into a post UKA knee.MethodsA retrospective review of a nationwide administrative claims database was performed from January 2015 to October 2020. Patients who underwent UKA and had an ipsilateral IACI were identified and matched 2:1 to a control group of primary UKA patients who did not receive IACI. Multivariate logistic analyses were conducted to assess differences in PJI rates at 6 months, 1 year, and 2 years.ResultsA total of 47,903 cases were identified, of which 2,656 (5.5%) cases received IACI. The mean time from UKA to IACI was 355 days. The incidence of PJI in the IACI group was 2.7%, compared to 1.3% in the control group. The rate of PJI after IACI was significantly higher than the rate in the control group at 6 months, 1 year, and 2 years (all P < .05). The majority of PJI occurred within the first 6 months following IACI (75%).ConclusionIn this study, IACI in a UKA doubled the risk of PJI compared to patients who did not receive an injection. Surgeons should be aware of this increased risk to aid in their decision-making about injecting into a UKA.Level of EvidenceIII, retrospective comparative study.     

Culturing Periprosthetic Joint Infection: Number of Samples,Growth Duration,and Organisms

Background

Owing to the difficulty isolating microorganisms in periprosthetic joint infection (PJI), current guidelines recommend that 3-5 intraoperative samples be cultured and maintained for 3-14 days. We investigated (1) the optimal number of culture samples and growth duration to diagnose PJI and (2) the microbiology profile at our institution.

Risk Factors for Periprosthetic Joint Infection Following Primary Total Hip Arthroplasty: A Case Control Study

The purpose of this study was to identify the specific comorbidities and demographic factors that are independently associated with an increased risk of periprosthetic joint infection (PJI) in total hip arthroplasty (THA) patients. A case–control study design was used to compare 88 patients who underwent unilateral primary THA and developed PJI with 499 unilateral primary THA patients who did not develop PJI. The impact of 18 comorbid conditions and other demographic factors on PJI was examined. Depression, obesity, cardiac arrhythmia, and male gender were found to be independently associated with an increased risk of PJI in THA patients. This information is important to consider when counseling patients on the risks associated with elective THA, and for risk-adjusting publicly reported THA outcomes.     

Positive Blood Cultures Decrease the Treatment Success in Acute Hematogenous Periprosthetic Joint Infection Treated With Debridement,Antibiotics, and Implant Retention

BackgroundThe influence of positive blood cultures on surgical outcome of acute hematogenous periprosthetic joint infection (PJI) treated by debridement, antibiotics, and implant retention (DAIR) remains unknown. This study evaluated the influence of positive blood cultures on the treatment success of DAIR in patients with acute hematogenous PJI.MethodsA retrospective chart review on 49 patients with blood culture data for acute hematogenous PJI was performed from 2005 to 2016 at a single institution. All patients were treated by DAIR and had a minimum follow-up of 1 year. Treatment success was defined by the Delphi criteria. Multivariate logistic regression analysis was performed to identify variables associated with positive blood culture and treatment success. Kaplan-Meier survivorship curves and log-rank tests were used for analysis.ResultsOverall, 44.9% (22/49) of blood cultures obtained yielded positive growth. Elevated Elixhauser comorbidity index was a significant risk factor associated with positive blood (adjusted odds ratio [OR], 1.65; 95% confidence interval [CI], 1.13-2.40; P = .049). A positive blood culture was the only significant factor predicting treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P = .026) after adjusting for confounding variables. Kaplan-Meier survivorship for infection-free implant survivorship was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with positive blood cultures (P = .037).ConclusionThe presence of positive blood cultures is associated with decreased treatment success of DAIR for acute hematogenous PJI. Patients with more comorbidities may need to be treated more aggressively for a favorable outcome.     

Concomitant Hip and Knee Periprosthetic Joint Infection in Periprosthetic Fracture: Diagnostic Utility of Serum and Synovial Fluid Markers

BackgroundDiagnosing periprosthetic joint infection (PJI) in patients with a periprosthetic fracture can be challenging due to concerns regarding the reliability of commonly used serum and synovial fluid markers. This study aimed at determining the diagnostic performance of serum and synovial fluid markers for diagnosing PJI in patients with a periprosthetic fracture of a total joint arthroplasty.MethodsA total of 144 consecutive patients were included: (1) 41 patients with concomitant PJI and periprosthetic fracture and (2) 103 patients with periprosthetic fracture alone. Serum markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and synovial markers white blood cell (WBC) count and polymorphonuclear percentage were assessed.ResultsESR demonstrated 87% sensitivity and 48% specificity at the Musculoskeletal Infection Society threshold, area under the curve (AUC) of 0.74, and optimal threshold of 45.5 mm/h (76% sensitivity, 68% specificity). CRP showed 94% sensitivity and 40% specificity, AUC of 0.68 with optimal threshold of 16.7 mg/L (84% sensitivity, 51% specificity). Synovial WBC count demonstrated 87% sensitivity and 78% specificity, AUC of 0.90 with optimal threshold of 4552 cells/μL (86% sensitivity, 85% specificity). Polymorphonuclear percentage showed 79% sensitivity and 63% specificity, AUC of 0.70 with optimal threshold of 79.5% (74% sensitivity, 63% specificity). The AUC of all combined markers was 0.90 with 84% sensitivity and 79% specificity.ConclusionThe diagnostic utility of the serum and synovial markers for diagnosing PJI was lower in the setting of concomitant periprosthetic fracture compared to PJI alone. Using the Musculoskeletal Infection Society thresholds, ESR, CRP, and WBC count showed high sensitivity, yet low specificity, thus higher thresholds and utilizing all serum and synovial markers in combination should be considered.     

Fungal Periprosthetic Joint Infection: A Review of Demographics and Management

BackgroundPeriprosthetic joint infection (PJI) is one of the most feared complications of total joint arthroplasty (TJA). Although commonly the result of colonization by Staphylococcal species, a growing number of cases of PJI with fungal pathogens have been reported within the last decade. Although standard treatment with two-stage exchange mirrors that of bacterial PJI, the variability in virulence between fungal species makes for an unpredictable and challenging treatment course.MethodsA review of Pubmed and Scopus from years 2009 to 2019 was conducted with the search terms fungal, infection, Candida, arthroplasty, periprosthetic, and prosthesis. Publications were reviewed and screened, yielding data for 286 patients with fungal PJI in the hip, knee, shoulder, and elbow prosthetics.ResultsPatient comorbidities generally included conditions impairing wound healing and immune response such as diabetes mellitus. Candida species were the most common fungal pathogens identified (85%); 30% had a concomitant bacterial infection. A two-stage exchange was most utilized, with a mean success rate of 65%. Antifungal impregnated spacers were utilized in 82 cases, with a comparatively high success rate (81%). Attempts at debridement with implant retention had substantially lower cure rates (15%).ConclusionsTwo-stage exchange is the favored approach to treating fungal PJI. Debridement with implant retention does not appear adequate to control infection, and retrieval of implanted materials should be prioritized. The use of antifungal impregnated spacers is an important area of ongoing research, with uncertainty regarding the type and quantity of antifungal agent to incorporate, although recent reports support the use of these agents.     

Clinical Outcome of Massive Endoprostheses Used for Managing Periprosthetic Joint Infections of the Hip and Knee

Background

Endoprosthetic replacement (EPR) is an option for management of massive bone loss resulting from infection around failed lower limb implants. The aim of this study is to determine the mid-term outcome of EPRs performed in the treatment of periprosthetic joint infection (PJI) and infected failed osteosyntheses around the hip and knee joint and identify factors that influence it.

Contemporary 2-Stage Treatment of Periprosthetic Hip Infection with Evidence-Based Standardized Protocols Yields Excellent Results: Caveats and Recommendations

BackgroundThis study quantified the effectiveness of contemporary and evidence-based standardized 2-stage treatment for periprosthetic hip infection. Findings illustrate potential limitations of criticisms of 2-stage protocols and potential consequences of adopting single-stage protocols before definitive data are available.MethodsFifty-four consecutive hips treated with 2-stage resection and reimplantation were retrospectively reviewed. Standardized protocols were adhered to including implant resection, meticulous surgical debridement, antibiotic spacer, 6-week intravenous antibiotics, a 2-week drug holiday, and laboratory assessment of infection eradication before reimplantation. After reimplantation, patients were placed on prophylactic intravenous antibiotics until discharge and discharged on oral antibiotics for a minimum of 7 days until intraoperative cultures were final. Successful treatment was defined per Delphi-based International Multidisciplinary Consensus.ResultsThe overall treatment success rate was 95.7% (44 of 46 cases) with mean infection-free survivorship of 67.2 (range, 23.8-106.4) months. Success rates were 100% for early and acute hematogenous infections regardless of host type and 100% for chronic infections in uncompromised hosts. 95% (19/20) of chronic infections in compromised hosts and 83.3% (5/6) of chronic infections in significantly compromised hosts were successfully treated. About 4% of primary hips and 20% of revision hips required repeat debridement and spacer exchange after initial resection. No patients died because of treatment.ConclusionDetails from this consecutive series of patients undergoing 2-stage treatment for hip infection suggest that some criticisms of 2-stage treatment as well as some arguments in support of single-stage treatment may be overstated. Promotion and uncritical adoption of single-stage treatment protocols are discouraged until further and more definitive data exist.     

Prevention of Periprosthetic Joint Infection: Examining the Recent Guidelines

Background

The global rise in infectious disease has led the Center for Disease Control and Prevention and the World Health Organization to release new guidelines for the prevention of surgical site infection.

Hip Disarticulation for Periprosthetic Joint Infection: Frequency,Outcome, and Risk Factors

BackgroundCurrently, the largest available series of hip disarticulation (HD) procedures performed for periprosthetic joint infection (PJI) includes only 6 patients. Given the lack of data on this dreadful outcome, we sought to determine the frequency of and risk factors for HD performed for a primary diagnosis of PJI.MethodsThe National Inpatient Sample from 1998 to 2016 was used to estimate the annual incidences of HD associated with PJI, elective primary total joint arthroplasty (control group 1), and other surgical procedures associated with PJI (control group 2) using National Inpatient Sample trend weights.ResultsOne-hundred forty-eight HDs for PJI, 2,378,313 primary total joint arthroplasty controls, and 51,580 PJI controls were identified. Median length-of-stay (11 days), proportion of patients with ≥5 comorbidities (22.8%), and median hospital costs ($25,895.60) were all greater for patients with HD compared with both control groups. The weighted frequency of HD hospitalizations increased by 366%, whereas the frequency of cases in control groups 1 and 2 increased by 93% and 310%, respectively, during the same timeframe. Upon multivariable logistic regression, age <65 years without private insurance (reference group: age ≥65 years without private insurance, odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.08-2.24), diabetes with chronic complications (OR: 1.91; 95% CI: 1.12-3.26), and peripheral vascular disease (OR: 2.59; 95% CI: 1.49-4.48) were significantly associated with increased risk of HD among all patients with PJI.ConclusionWhile the overall frequency of lower extremity amputations may be decreasing, our study documents an alarming increase in the frequency of HD for PJI during the study period. Patients under age 65 years without private insurance were at significantly higher risk of HD among patients with PJI.     

Mortality During Total Knee Periprosthetic Joint Infection

Background

Periprosthetic joint infections (PJIs) are fraught with multiple complications including poor patient-reported outcomes, disability, reinfection, disarticulation, and even death. We sought to perform a systematic review asking the question: (1) What is the mortality rate of a PJI of the knee undergoing 2-stage revision for infection? (2) Has this rate improved over time? (3) How does this compare to a normal cohort of individuals?

Diagnosis and Treatment of Culture-Negative Periprosthetic Joint Infection

Identification of the causative organism(s) in periprosthetic joint infection (PJI) is a challenging task. The shortcomings of traditional cultures have been emphasized in recent literature, culminating in a clinical entity known as “culture-negative PJI.” Amidst the growing burden of biofilm infections that are inherently difficult to culture, the field of clinical microbiology has seen a paradigm shift from culture-based to molecular-based methods. These novel techniques hold much promise in the demystification of culture-negative PJI and revolutionization of the microbiology laboratory. This article outlines the clinical implications of culture-negative PJI, common causes of this diagnostic conundrum, established strategies to improve culture yield, and newer molecular techniques to detect infectious organisms.     

Periprosthetic Joint Infection in Patients with Inflammatory Joint Disease: a Review of Risk Factors and Current Approaches to Diagnosis and Management

Background

Prevention, early identification, and effective management of periprosthetic joint infection (PJI) in patients with inflammatory joint disease (IJD) present unique challenges for physicians. Discontinuing disease-modifying anti-rheumatoid drugs (DMARDs) perioperatively may reduce immunosuppression and infection risk at the expense of increasing disease flares. Interpreting traditional diagnostic markers of PJI can be difficult due to disease-related inflammation.

Purposes

This review is designed to answer how to (1) manage immunosuppressive/DMARD therapy perioperatively, (2) diagnose PJI in patients with IJD, and (3) treat PJI in this population.

Methods

The PubMed database was searched for relevant articles with subsequent review by independent authors.

Results

While there is evidence to support the use of methotrexate perioperatively in RA patients, it remains unclear whether using anti-tumor necrosis factor medications perioperatively increases the risk of surgical site infections. Serum erythrocyte sedimentation rate and C-reactive protein can be useful for diagnosis of PJI in this population, but only as part of comprehensive workup that ultimately relies upon sampling of joint fluid. Management of PJI depends on several clinical factors including duration of infection and the likelihood of biofilm presence, the infecting organism, sensitivity to antibiotic therapy, and host immune status. The evidence suggests that two-stage revision or resection arthroplasty is more likely to eradicate infection, particularly when MRSA is the pathogen.

Conclusion

Immunosuppression and baseline inflammatory changes in the IJD population can complicate the prevention, diagnosis, and treatment of PJI. Understanding the increase in risk associated with IJD and its treatment is essential for proper management when patients undergo lower extremity arthroplasty.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9338-8) contains supplementary material, which is available to authorized users.     

Worse Outcomes Are Associated With Proximal Femoral Replacement Following Periprosthetic Joint Infection

BackgroundProximal femoral replacements (PFRs) are often used in the setting of severe bone loss. As osteolysis has become less common, PFR may be used to address other causes of bone loss such as infection or periprosthetic fracture. The aim of this study is to investigate the clinical outcomes of PFR for non-neoplastic conditions.MethodsA retrospective review of 46 patients undergoing PFR at a single institution was performed. The electronic records were reviewed to extract relevant information including the reason for use of PFR, surgical variables, follow-up, and complications. Survivorship curves were generated and differences in survivorship were evaluated using the log-rank test. Radiographic evaluation was also performed.ResultsUsing revision as an endpoint, the Kaplan-Meier analysis of the entire cohort demonstrated a survival rate of 74% at 1 year and 67% at 5 years. Patients with a preoperative diagnosis of periprosthetic joint infection demonstrated the lowest survivorship with a failure rate of 47%. Furthermore, a high dislocation rate at 17.4% (n = 8) was observed. The use of dual-mobility articulation was effective in reducing dislocation.ConclusionPFR is a valuable reconstructive option for patients with massive proximal femoral bone loss. This study demonstrates that patients with periprosthetic joint infection who undergo PFR reconstruction are at very high risk of subsequent failure, most commonly from reinfection and instability. The use of a dual-mobility articulation in association with PFR appears to help mitigate risk of subsequent dislocation.