Moving Beyond Systemic Inflammatory Response Syndrome and Bacteremia: Are Modern Critical Care Calculators Useful in Predicting Debridement, Antibiotics, and Implant Retention Treatment Outcomes in Periprosthetic Joint Infection?

BACKGROUND: In critically ill periprosthetic joint infection (PJI) patients, surgeons need to balance the need for aggressive, definitive treatment against the health state of a potentially unstable patient. A clear understanding of the association between treatment outcomes and assessment scores for sepsis would benefit clinical decision-making in these urgent cases. The current study evaluates the effect of critical illness on debridement, antibiotics, and implant retention (DAIR) outcomes, as defined by systemic inflammatory response syndrome (SIRS) and, for the first time, by contemporary markers quick Sequential Organ Failure Assessment (qSOFA) and Modified Early Warning Score (MEWS). METHODS: We retrospectively identified 253 patients who underwent DAIR for PJI at a single institution between 2017 and 2021. The SIRS, qSOFA, and MEWS scores were calculated based on variables on admission. A DAIR treatment failure, defined as reoperation or mortality, was measured at 90 days and two years. Univariate analysis was used to determine the association between elevated critical care scores and DAIR failure. RESULTS: The DAIR treatment success was 59% at two years, with hip procedures and Charlson comorbidity index (CCI) ≥ 1 independently associated with higher odds of DAIR failure. There were 43 patients (16%) who presented with SIRS, however, only four (2%) had positive qSOFA scores. Neither SIRS nor qSOFA were predictive of DAIR failure. For knees only, elevated MEWS scores were predictive of 90-day DAIR failure (P = 0.019). CONCLUSION: Over one in six patients undergoing DAIR for PJI presented with SIRS, while only one in 50 had a positive qSOFA. The SIRS and qSOFA scores were not predictive of DAIR failure. Elevated MEWS scores were associated with DAIR failure at 90 days postoperatively in knee PJIs only, and should be confirmed in a larger cohort. Our results suggest that SIRS is not predictive of DAIR outcomes, possibly because it overestimates the proportion of critically ill patients.

Perioperative Glycemic Variability Influences Infection Rates Differently Following Revision Hip and Knee Arthroplasty.

BACKGROUND: Recent investigations have determined that abnormal postoperative glycemia following primary total joint arthroplasty is associated with adverse events. Our study aimed to determine if hyperglycemia and glycemic variability following aseptic revision total joint arthroplasty were associated with periprosthetic joint infection (PJI) within two years postoperatively. METHODS: A retrospective review was performed of 2,208 patients within a single institution undergoing aseptic revision total joint arthroplasty from 2012 to 2019. Postoperative glucose values were recorded. Glycemic variability was measured via three parameters: coefficient of variation, mean amplitude of glycemic excursions, and J-index. Logistic regression analyses were performed to examine associations with PJI at 90-day, 1-, and 2-year follow-up. RESULTS: In revision hips, all glycemic measures were not associated with PJI at any time point in logistic regression analyses, except for the mean amplitude of glycemic excursions, which predicted PJI at one year (P = 0.045); body mass index was the only factor associated with PJI at all timepoints in all models. In revision knees, all glycemic measures were not associated with PJI at any timepoint in logistic regression analyses; however, PJI rates differed between diabetics and nondiabetics at all time points (P < 0.05). CONCLUSIONS: Our findings illustrate that decreasing preoperative body mass index and postoperative glycemic variability may be critical in reducing PJI rates in revision hips. Furthermore, patients who have diabetes should be counseled that they remain at higher risk of PJI regardless of perioperative glucose control after revision knee surgery.

Periprosthetic Joint Infection in Patients With Inflammatory Arthritis: Optimal Tests to Differentiate From Flares.

OBJECTIVE: Diagnosis of periprosthetic joint infection (PJI) in patients with inflammatory arthritis (IA) is challenging, as features of IA flares can mimic infection. We aimed to cross-sectionally determine if the optimal tests to diagnose PJI in osteoarthritis were present in patients with IA flares. METHODS: We enrolled patients from October 2020 to July 2022 in 3 groups: (a) PJI-total joint arthroplasty patients undergoing revision for infection, (b) IA Flare-IA patients with a flaring native joint, and (c) IA Aseptic-total joint arthroplasty patients with IA undergoing aseptic arthroplasty revision. We compared blood and synovial fluid markers between the cohorts using Kruskal-Wallis and Fisher exact tests to assess marker sensitivity and specificity. RESULTS: Of 52 cases overall, 40% had rheumatoid arthritis, 20% psoriatic arthritis, and 11% osteoarthritis (in PJI group). PJI cases had higher C-reactive protein (CRP) and synovial fluid polymorphonuclear neutrophil percentage (%PMN). Alpha-defensin tested positive in 93% of PJI cases, 20% of IA Flares, and 6% of IA Aseptic (p < 0.01). Synovial white blood cell count >3000/µL and positive alpha-defensin were highly sensitive (100%) in diagnosing infection; however, specificity was 50% for white blood cell counts and 79% for alpha-defensin. PJI diagnosis was nearly 5 times more likely with positive alpha-defensin and almost 6 times more likely with %PMNs >80. Blood markers interleukin-6, procalcitonin, and d-dimer were neither sensitive nor specific, whereas erythrocyte sedimentation rate and CRP showed 80% sensitivity, but 47% and 58% respective specificities. CONCLUSIONS: Although synovial %PMNs, CRP, and alpha-defensin are sensitive tests for diagnosing PJI, they are less specific and may be positive in IA flares.

Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis.

Translesion DNA synthesis (TLS) is a cellular process that enables the bypass of DNA lesions encountered during DNA replication and is emerging as a primary target of chemotherapy. Among vertebrate DNA polymerases, polymerase κ (Polκ) has the distinctive ability to bypass minor groove DNA adducts in vitro. However, Polκ is also required for cells to overcome major groove DNA adducts but the basis of this requirement is unclear. Here, we combine CRISPR base-editor screening technology in human cells with TLS analysis of defined DNA lesions in Xenopus egg extracts to unravel the functions and regulations of Polκ during lesion bypass. Strikingly, we show that Polκ has two main functions during TLS, which are differentially regulated by Rev1 binding. On the one hand, Polκ is essential to replicate across a minor groove DNA lesion in a process that depends on PCNA ubiquitylation but is independent of Rev1. On the other hand, through its cooperative interaction with Rev1 and ubiquitylated PCNA, Polκ appears to stabilize the Rev1-Polζ extension complex on DNA to allow extension past major groove DNA lesions and abasic sites, in a process that is independent of Polκ's catalytic activity. Together, our work identifies catalytic and noncatalytic functions of Polκ in TLS and reveals important regulatory mechanisms underlying the unique domain architecture present at the C-terminal end of Y-family TLS polymerases.

Effects of antiseptic irrigation solutions on osseointegration in a cementless tibial implantation mouse model.

Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H2O2) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H2O2, or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications.

Temporal Trends in the Rate of Revision Total Knee Arthroplasty for Prosthetic Joint Infection.

Background: Perioperative practices have been introduced over the last decade to decrease the risk of periprosthetic joint infection (PJI). We sought to determine whether rates of revision total knee arthroplasty (TKA) for PJI decreased during the period 2006-2016. Methods: This observational cohort study used data from the New York Statewide Planning and Research Cooperative System to identify patients undergoing TKA in 2006-2016. Data through 2017 were used to determine if patients underwent revision TKA for PJI (including debridement, antibiotics and implant retention) within 1 year of the primary surgery. A generalized estimating equation model, clustered by hospital, was used to examine the impact of time on likelihood of revision TKA for PJI. Results: In 2006-2016, 233,165 primary TKAs performed were included. Mean age was 66.1 (standard deviation 10.3) years, and 65% were women. Overall, 0.5% of the patients underwent revision TKA for PJI within 1 year of surgery. The generalized estimating equation model showed that for primary TKA performed in 2006-2013, year of surgery did not impact the likelihood of revision TKA for PJI (odds ratio 1.00, 95% confidence interval 0.97-1.03, P = .9221), but that for primary TKA performed in 2014-2016, the likelihood decreased by year (odds ratio 0.76, 95% confidence interval 0.66-0.88, P = .0002). Conclusions: The likelihood of revision TKA for PJI was stable from 2006 to 2013 but declined during the period 2014-2016 across patient and hospital categories. This decline could be due to infection mitigation strategies or other unmeasured factors.

Staphyloccocus aureus biofilm, in absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes.

Staphyloccocus aureus (S. aureus) is a major bacterial pathogen in orthopedic periprosthetic joint infection (PJI). S. aureus forms biofilms that promote persistent infection by shielding bacteria from immune cells and inducing an antibiotic-tolerant metabolic state. We developed an in vitro system to study S. aureus biofilm interactions with primary human monocytes in the absence of planktonic bacteria. In line with previous in vivo data, S. aureus biofilm induced expression of inflammatory genes such as TNF and IL1B, and their anti-inflammatory counter-regulator IL10. S. aureus biofilm also activated expression of PD-1 ligands, and IL-1RA, molecules that have the potential to suppress T cell function or differentiation of protective Th17 cells. Gene induction did not require monocyte:biofilm contact and was mediated by a soluble factor(s) produced by biofilm-encased bacteria that was heat resistant and >3 kD in size. Activation of suppressive genes by biofilm was sensitive to suppression by Jak kinase inhibition. These results support an evolving paradigm that biofilm plays an active role in modulating immune responses, and suggest this occurs via production of a soluble vita-pathogen-associated molecular pattern, a molecule that signals microbial viability. Induction of T cell suppressive genes by S. aureus biofilm provides insights into mechanisms that can suppress T cell immunity in PJI.

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] ( p = 0.009 ) 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.

The Infected Polypropylene Mesh: When Does Biofilm Form and Which Antiseptic Solution Most Effectively Removes It?

BACKGROUND: Polypropylene (PPE) mesh is commonly utilized to reconstruct catastrophic extensor mechanism disruptions in revision total knee arthroplasty. Unfortunately, these procedures are associated with a high rate of periprosthetic joint infection. The purpose of the current study was to: 1) visualize and quantify the progression of bacterial biofilm growth on PPE-mesh; and 2) determine which antiseptic solutions effectively remove viable bacteria. METHODS: Knitted PPE mesh samples were cultured with either methicillin-sensitive Staphylococcus aureus (MSSA) or Escherichia coli (E. coli) for 7 days, with regular quantification of colony forming units (CFUs) and visualization using scanning electron microscopy to identify maturity. Immature (24 hour) and mature (72 hour) biofilm was treated with one of 5 commercial antiseptics for 3 minutes. A 0.05% chlorhexidine gluconate, a surfactant-based formulation of ethanol, acetic acid, sodium acetate, benzalkonium chloride, diluted povidone-iodine (0.35%), undiluted (10%) povidone-iodine, and 1:1 combination of 10% povidone-iodine and 3% hydrogen peroxide. A 3-log reduction in CFUs compared to saline was considered clinically meaningful. RESULTS: The CFU counts plateaued, indicating maturity, at 72 hours for both MSSA and E. coli. The scanning electron microscopy confirmed confluent biofilm formation after 72 hours. The 10% povidone-iodine was clinically effective against all MSSA biofilms and immature E. coli biofilms. The 10% povidone-iodine with hydrogen peroxide was effective in all conditions. Only 10% povidone iodine formulations produced significantly (P < .0083) reduced CFU counts against mature biofilms. CONCLUSIONS: Bacteria rapidly form biofilm on PPE mesh. Mesh contamination can be catastrophic, and clinicians should consider utilizing an antiseptic solution at the conclusion of mesh implantation. Undiluted povidone-iodine with hydrogen peroxide should be considered when attempting to salvage infected PPE mesh.

Do one-stage indications predict success following two-stage arthroplasty for chronic periprosthetic joint infection?

Introduction: The 2018 International Consensus Meeting (ICM) proposed criteria for one-stage exchange arthroplasty in treating periprosthetic joint infection (PJI). Our study aimed to determine what proportion of PJI patients met the 2018 ICM criteria and how this affected infection-free survivorship for patients. Methods: All chronic PJI patients treated with two-stage exchange within our institution between 2017-2020 were retrospectively reviewed. Included cases met 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI and had a 2-year minimum follow-up. Treatment success was defined as Tier 1A in the 2019 MSIS working group definition. ICM one-stage criteria included non-immunocompromised host, absence of sepsis, adequate soft tissue for closure, known preoperative pathogen, and susceptibility. Immunocompromised host was analyzed as two separate definitions. Kaplan-Meier survivorship, Cox regression, and univariate analyses were performed. Results: A total of 293 chronic PJI patients were included. Overall, treatment failure occurred in 64/293 (21.8 %) patients. Only 13 % (n=37) met ICM criteria definition no. 1 for one-stage exchange; 12 % (n=33) met definition no. 2. In both definitions, infection-free survivorship at 2 years did not differ between patients who met and did not meet criteria (p>0.05). Cox proportional hazard regression analyses demonstrated that the only variable predicting treatment failure was knee joint involvement (p=0.01). Conclusions: We found that a very limited number of chronic PJI patients were suitable for a one-stage exchange. Furthermore, the supposition that healthier hosts with known pathogens (the basis of the ICM criteria) yield better PJI treatment outcomes was not observed. These results justify the ongoing multicenter randomized control trial comparing one-stage versus two-stage treatment for chronic PJI.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

Folding of Class IIa HDAC Derived Peptides into α-helices Upon Binding to Myocyte Enhancer Factor-2 in Complex with DNA.

Interaction of transcription factor myocyte enhancer factor-2 (MEF2) family members with class IIa histone deacetylases (HDACs) has been implicated in a wide variety of diseases. Though considerable knowledge on this topic has been accumulated over the years, a high resolution and detailed analysis of the binding mode of multiple class IIa HDAC derived peptides with MEF2D is still lacking. To fulfil this gap, we report here the crystal structure of MEF2D in complex with double strand DNA and four different class IIa HDAC derived peptides, namely HDAC4, HDAC5, HDAC7 and HDAC9. All class IIa HDAC derived peptides form extended amphipathic α-helix structures that fit snugly in the hydrophobic groove of MEF2D domain. Binding mode of class IIa HDAC derived peptides to MEF2D is very similar and occur primarily through nonpolar interactions mediated by highly conserved branched hydrophobic amino acids. Further studies revealed that class IIa HDAC derived peptides are unstructured in solution and appear to adopt a folded α-helix structure only upon binding to MEF2D. Comparison of our peptide-protein complexes with previously characterized structures of MEF2 bound to different co-activators and co-repressors, highlighted both differences and similarities, and revealed the adaptability of MEF2 in protein-protein interactions. The elucidation of the three-dimensional structure of MEF2D in complex with multiple class IIa HDAC derived peptides provide not only a better understanding of the molecular basis of their interactions but also have implications for the development of novel antagonist.

When to lavage in the absence of a sonographically visible joint effusion in painful total knee arthroplasty: a retrospective longitudinal study.

OBJECTIVE: To determine if knee arthroplasty without sonographically visible effusion needs to undergo lavage to rule out infection. METHODS: Patients were accrued by a retrospective search of a longitudinally maintained radiology database looking for patients referred for ultrasound guided aspiration of suspected TKA infection. Clinical presentations, laboratory tests, intraoperative findings, and follow-up were reviewed. RESULTS: Four hundred sixty-nine patients were included (mean age of 67 years (range, 36-91)) including 251 females. Four hundred three patients had effusions, of which 57 were infected based on ultrasound-guided and surgical aspirates. Sixty-four patients lacked effusions, of which 47 underwent lavage at the clinicians' request, with 6/47 infected. Nineteen patients without effusion were not lavaged at the clinicians' request due to low suspicion, and none were infected. Patients with positive lavage cultures all had clinical risk factors. Infection rates were significantly higher in patients with joint effusion and clinical suspicion for infection compared to absent joint effusion and absent clinical suspicion. A significantly higher proportion of patients with hyperemia or moderate-severe synovial thickening on ultrasound were symptomatic and had joint effusion and positive joint cultures. Aspiration of native fluid had 85% sensitivity and 100% specificity while lavage had a sensitivity of 57% and specificity of 100%. Negative predictive value for native aspirates was 94% compared to 86% for lavage. CONCLUSION: A TKA with low clinical suspicion of infection does not need to undergo lavage in the absence of a sonographically visible effusion.

Robotics and Navigation Do Not Affect the Risk of Periprosthetic Joint Infection Following Primary Total Hip Arthroplasty: A Propensity Score-Matched Cohort Analysis.

BACKGROUND: The use of computer navigation or robotic assistance during primary total hip arthroplasty (THA) has yielded numerous benefits due to more accurate component positioning. The utilization of these tools is generally associated with longer operative times and also necessitates additional surgical equipment and personnel in the operating room. Thus, the aim of this study was to evaluate the impact of technology assistance on periprosthetic joint infection (PJI) after primary THA. METHODS: We retrospectively reviewed the records for 12,726 patients who had undergone primary THA at a single high-volume institution between 2018 and 2021. Patients were stratified by surgical technique (conventional THA, computer-navigated THA [CN-THA], or robotic-assisted THA [RA-THA]) and were matched 1:1 with use of propensity score matching. Univariate and logistic regression analyses were performed to compare the rates of PJI within 90 days postoperatively between the cohorts. RESULTS: After propensity score matching, there were 4,006 patients in the THA versus RA-THA analysis (2,003 in each group) and 5,288 patients in the THA versus CN-THA analysis (2,644 in each group). CN-THA (p < 0.001) and RA-THA (p < 0.001) were associated with longer operative times compared with conventional THA by 3 and 11 minutes, respectively. The rates of PJI after conventional THA (0.2% to 0.4%) were similar to those after CN-THA (0.4%) and RA-THA (0.4%). On the basis of logistic regression, the development of PJI was not associated with the use of computer navigation (odds ratio [OR], 1.8 [95% confidence interval (CI), 0.7 to 5.3]; p = 0.232) or robotic assistance (OR, 0.9 [95% CI, 0.3 to 2.3]; p = 0.808). CONCLUSIONS: Despite longer operative times associated with the use of computer navigation and robotic assistance, the use of these tools was not associated with an increased risk of PJI within 90 days after surgery. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Development of Diagnostic Quality Metrics for Prosthetic Joint Infection.

ABSTRACT: Although well-accepted clinical practice guidelines exist for the diagnosis of prosthetic joint infection (PJI), little is known about the quality of diagnosis for PJI. The identification of quality gaps in the diagnosis of PJI would facilitate the development of care structures and processes to shorten time to diagnosis and reduce the significant morbidity, mortality, and economic burden associated with this condition. Hence, we sought to develop valid clinical quality measures to improve the timeliness and accuracy of PJI diagnosis. We convened a nine-member multidisciplinary national panel of PJI experts including orthopedic surgeons, infectious disease specialists, an emergency medicine physician, and a patient previously treated for PJI to review, discuss, and rate the validity of proposed measures using a modification of the RAND-UCLA appropriateness method. In total, 57 permutations of six proposed measures were rated. Populations considered to be at high enough risk for PJI that certain care processes should always be performed were identified by the panel. Among the proposed quality measures, the panel rated five as valid. These novel clinical quality measures could provide insight into care gaps in the diagnosis of PJI.

Outcomes after débridement, antibiotics, and implant retention for prosthetic joint infection in shoulder arthroplasty.

BACKGROUND: Patients who undergo total shoulder arthroplasty usually have excellent long-term outcomes. However, a subset of patients is diagnosed with a prosthetic joint infection (PJI) requiring revision procedures and prolonged recovery. The purpose of this study was to evaluate rates of recurrent shoulder PJI in patients undergoing débridement, antibiotics, and implant retention (DAIR), single-stage revision, and 2-stage revision. We also sought to compare outcomes and complications across procedures. METHODS: Retrospective chart review was conducted for patients diagnosed with PJI after primary shoulder arthroplasty between January 2010 and August 2021. Patients were included if they underwent treatment with DAIR, single-stage revision, or 2-stage revision. Demographic information, surgical details, complications, laboratory data, postoperative antibiotic regimen, and infectious pathogen were collected. Postoperative patient-reported outcomes were collected: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, Shoulder Activity Scale, and PROMIS Upper Extremity. Chi-square, t test, and 1-way analysis of variance were used as appropriate to evaluate each factor. RESULTS: Sixty-five patients were included in the study, 26% treated with DAIR, 9% treated with single-stage revision, and 65% treated with 2-stage revision. There were no significant differences in patient comorbidities. Patients undergoing DAIR were diagnosed significantly earlier than those undergoing single- and 2-stage revision procedures (12.6 ± 22.9 months vs. 49.6 ± 48.4 vs. 25.0 ± 26.6, P = .010). Recurrent PJI was noted in 23.1% of patients: 29.4% of DAIR patients, no single-stage patients, and 23.8% of 2-stage patients (P = .330). Patients undergoing 2-stage revision with treatment failure had a significantly higher Elixhauser Comorbidity Index (0.2 ± 3.7 vs. 3.7 ± 3.9, P = .027). There was no significant difference in patient-reported outcomes across groups. CONCLUSION: Patients undergoing treatment of shoulder PJI with DAIR did not have an increased rate of reinfection compared with single-stage and 2-stage revision procedures. Patients treated with DAIR were diagnosed with PJI significantly earlier than those undergoing single-stage and 2-stage revision procedures. There was no difference in complication rates between groups. This information adds to the body of work detailing outcomes after DAIR for shoulder PJI and provides encouraging data for use in this patient population. Future studies with a larger sample size may be conducted to further investigate specific pathogens, infection timelines, and antibiotic regimens that reduce the risk of treatment failure.

Does Computer Navigation or Robotic Assistance Affect the Risk of Periprosthetic Joint Infection in Primary Total Knee Arthroplasty? A Propensity Score-Matched Cohort Analysis.

BACKGROUND: The use of technology during total knee arthroplasty (TKA) has been associated with more accurate component position and less blood loss. Yet to date, the risk of developing prosthetic joint infection (PJI) associated with computer navigation (CN) or robotic assistance (RA) has not been thoroughly evaluated. This study used propensity score-matching (PSM) in a large cohort of primary TKA patients to compare the rate of PJI following conventional TKA (TKA) versus CN-TKA and RA-TKA. METHODS: We retrospectively reviewed 13,015 knees in 11,727 patients who underwent primary TKA at a single institution from 2018 to 2021. The cohort was stratified into TKA, CN-TKA, and RA-TKA groups. 1:1 PSM was applied to 11,834 patients. Propensity score-matching was performed using logistic regression accounting for age, sex, body mass index, Charlson Comorbidity Index (CCI) score, CCI components, and smoking status. Univariate and multivariable analyses were performed to evaluate differences in surgical time and PJI rate. RESULTS: Significantly longer median operating times were noted in the RA-TKA group (14 minutes) compared to TKA (P < .001). The PJI rates among matched cohorts were similar among RA-TKA (0.3%), CN-TKA (0.3%), and conventional TKA (0.5%). Multivariable logistic regressions demonstrated that the use of robotic assistance (odds ratio (OR) = 0.5, P = .423) or computer navigation (OR = 0.61, P = .128) was not associated with increased risk of PJI when compared to conventional TKA. CONCLUSIONS: Use of computer navigation and robotic assistance during primary TKA are associated with longer surgical times, but no difference in PJI frequency within 90 days of surgery.

Dalbavancin is thermally stable at clinically relevant temperatures against methicillin-sensitive Staphylococcus Aureus.

Introduction: While the rate of orthopaedic infections has remained constant over the years, the burden on healthcare systems continues to rise with an aging population. Local antibiotic delivery via polymethyl methacrylate bone cement is a common adjunct in treating bone and joint infections. Dalbavancin is a novel lipoglycopeptide antibiotic in the same class as vancomycin that has shown efficacy against Gram-positive organisms when used systemically but has not been investigated as a local antibiotic. This study aims to identify whether dalbavancin is thermally stable at the temperatures expected during the polymerization of polymethyl methacrylate cement. Methods: Stock solutions of dalbavancin were prepared and heated using a polymerase chain reaction machine based upon previously defined models of curing temperatures in two clinically relevant models: a 10 mm polymethyl methacrylate bead and a polymethyl methacrylate articulating knee spacer model. Aliquots of heated dalbavancin were then transferred to be incubated at core body temperature (37 ∘C) and analyzed at various time points up to 28 d. The minimum inhibitory concentration at which 90 % of colonies were inhibited (MIC90) for each heated sample was determined against methicillin-sensitive Staphylococcus aureus (American Type Culture Collection, ATCC, 0173K) using a standard microbroth dilution assay. Results: The average MIC90 of dalbavancin was 1.63 µgmL-1 ±0.49 against 0173K S. aureus. There were no significant differences in the relative MIC90 values after heating dalbavancin in either model compared to unheated control dalbavancin. Conclusions: Dalbavancin is thermally stable at the curing temperatures of polymethyl methacrylate cement and at human core body temperature over 28 d. Future in vitro and in vivo studies are warranted to further investigate the role of dalbavancin as a local antibiotic prior to its clinical use.

Which Combination is the Best? A Comparison of the Predictive Potential of Serum Biomarker Combinations to Diagnose Periprosthetic Joint Infection.

BACKGROUND: Without a gold-standard test, recent periprosthetic joint infections (PJI) literature has explored the utility of combining serological results, with promising findings. However, previous studies evaluated fewer than 200 patients and often studied only 1 to 2 test combinations. The purpose of this study was to accumulate a large single-institution cohort of revision total joint arthroplasty (rTJA) patients to determine the diagnostic utility of combination serum biomarkers to identify PJI. METHODS: A single institution longitudinal database was assessed to identify all patients who underwent rTJA from 2017 to 2020. There were 1,363 rTJA patients (715 rTKA patients and 648 rTHA patients) including 273 PJI cases (20%) analyzed. The PJI was diagnosed post-rTJA utilizing 2011 Musculoskeletal Infection Society (MSIS) criteria. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, and interleukin 6 (IL-6) were systematically collected for all patients. RESULTS: The rTKA combination markers of CRP + ESR (sensitivity: 78.3%, specificity: 88.8%, positive predictive value (PPV): 70.0%, negative predictive value (NPV): 92.5%), CRP + D-dimer (sensitivity: 60.5%, specificity: 92.6%, PPV: 63.4%, NPV: 91.7%), and CRP + IL-6 (sensitivity: 38.5%, specificity: 100.0%, PPV: 100.0%, NPV: 92.9%) all yielded higher specificity than CRP alone (sensitivity: 94.4%, specificity: 75.0%, PPV: 55.5%, NPV: 97.6%). Similarly, the rTHA combination markers of CRP + ESR (sensitivity: 70.1%, specificity: 88.8%, PPV: 58.1%, NPV: 93.1%), CRP + D-dimer (sensitivity: 57.1%, specificity: 90.1%, PPV: 43.2%, NPV: 94.1%), and CRP + IL-6 (sensitivity: 21.4%, specificity: 98.4%, PPV: 60.0%, NPV: 91.7%) all yielded higher specificity than CRP alone (sensitivity: 84.7%, specificity: 77.5%, PPV: 45.4%, NPV: 95.8%). CONCLUSION: Overall, in diagnosing PJI for both rTKA and rTHA, 2-marker combinations yielded higher specificity, while 3-marker combinations yielded higher sensitivity compared to CRP alone. However, compared to all 2-marker and 3-marker combinations, CRP demonstrated superior overall diagnostic utility. These findings suggest that routine combination testing of markers for PJI diagnosis may be excessive and an unnecessary use of resources, especially in resource-limited situations.